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Sample records for evaluate local drug

  1. Using Statewide Youth Surveys to Evaluate Local Drug Use Policies and Interventions

    OpenAIRE

    Paschall, Mallie J.; Flewellng, Robert L.; Grube, Joel W.

    2009-01-01

    This article summarizes two studies that use statewide school-based youth surveys to evaluate local initiatives to reduce alcohol and other substance abuse. The Vermont “New Directions” evaluation was conducted to assess the effects of a community-based intervention in 23 Vermont communities to reduce youth substance use. Outcome data were obtained from the Youth Risk Behavior Survey, which is administered to students in grades 8 through 12 every other year in almost all school districts in t...

  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 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

  4. Local anesthetics: dentistry's most important drugs.

    Science.gov (United States)

    Malamed, S F

    1994-12-01

    One hundred and fifty years ago, Horace Wells opened the door to local anesthetics. Since then, many advances have been made in pain control. The development of dentistry's most important drugs is highlighted here.

  5. 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

  6. Localizing seizure-onset zones in presurgical evaluation of drug-resistant epilepsy by electroencephalography/fMRI: effectiveness of alternative thresholding strategies.

    Science.gov (United States)

    Hauf, M; Jann, K; Schindler, K; Scheidegger, O; Meyer, K; Rummel, C; Mariani, L; Koenig, T; Wiest, R

    2012-10-01

    Simultaneous EEG/fMRI is an effective noninvasive tool for identifying and localizing the SOZ in patients with focal epilepsy. In this study, we evaluated different thresholding strategies in EEG/fMRI for the assessment of hemodynamic responses to IEDs in the SOZ of drug-resistant epilepsy. Sixteen patients with focal epilepsy were examined by using simultaneous 92-channel EEG and BOLD fMRI. The temporal fluctuation of epileptiform signals on the EEG was extracted by independent component analysis to predict the hemodynamic responses to the IEDs. We applied 3 different threshold criteria to detect hemodynamic responses within the SOZ: 1) PA, 2) a fixed threshold at P signal correlates in 11 of 16, and FAV in 13 of 16 patients. Hemodynamic responses were detected within the resected areas in 5 (PA), 6 (FWE), and 8 (FAV) of 10 patients who remained seizure-free after surgery. EEG/fMRI is a noninvasive tool for the presurgical work-up of patients with epilepsy, which can be performed during seizure-free periods and is complementary to the ictal electroclinical assessment. Our findings suggest that the effectiveness of EEG/fMRI in delineating the SOZ may be further improved by the additional use of alternative analysis strategies such as FAV.

  7. Feasibility of localized immunosuppression: 3. Preliminary evaluation of organosilicone constructs designed for sustained drug release in a cell transplant environment using dexamethasone.

    Science.gov (United States)

    Song, Y; Margolles-Clark, E; Fraker, C A; Weaver, J D; Ricordi, C; Pileggi, A; Stabler, C L; Buchwald, P

    2012-05-01

    As part of our ongoing effort to develop biohybrid devices for pancreatic islet transplantation, we are interested in establishing the feasibility of a localized immune-suppressive approach to avoid or minimize the undesirable side effects of existing systemic treatments. Since biohybrid devices can also incorporate biocompatible scaffold constructs to provide a support environment for the transplanted cells that enhances their engraftment and long-term function, we are particularly interested in an approach that would use the same three-dimensional construct, or part of the same construct, to also provide sustained release of therapeutic agents to modulate the inflammatory and immune responses locally. Within this framework, here, we report preliminary results obtained during the investigation of the suitability of organosilicone constructs for providing sustained localized drug release using small, matrix-type polydimethylsiloxane (PDMS) disks and dexamethasone as a model hydrophobic drug. Following a short burst, long-term steady sustained release was observed under in vitro conditions at levels of 0.1-0.5 microg/day/disk with a profile in excellent agreement with that predicted by the Higuchi equation. To verify that therapeutic levels can be achieved, suppression of LPS-induced activation has been shown in THP-1 cells with disks that have been pre-soaked for up to 28 days. These preliminary results prove the feasibility of this approach where an integral part of the biomaterial construct used to enhance cell engraftment and long-term function also serves to provide sustained local drug release.

  8. Formulation of an antispasmodic drug as a topical local anesthetic.

    Science.gov (United States)

    Abdel-Hamid, Sameh M; Abdel-Hady, S E; El-Shamy, A A; El-Dessouky, H F

    2006-12-01

    Mebeverine hydrochloride, a spasmolytic agent on GIT smooth muscles, was reported to have a local anesthetic effect. Thus, it was desired in this study to formulate mebeverine HCl into a gel that could be used locally in the treatment of different oral painful conditions. Poloxamer 407 (P-407) was used as the base for this gel. Different additives were used to enhance drug release from the preparation while others were used to enhance the residence time for the preparation. Different formulae were characterized in terms of drug release and mucoadhesion. The formula which has shown the best compromise between the aforementioned parameters was selected for clinical evaluation in comparison to Lidocaine HCl gel and rheologically examined. The best drug release enhancer was cetrimide (0.005%, w/w), while hydroxypropylcellulose (0.5%, w/w) as a mucoadhesive additive has shown the best compromise between fast drug release and mucoadhesion. The gel formula (G) has shown a better pain reduction efficiency (p=0.0078) and longer duration (p=0.0313) than Lidocaine HCl gel. Histopathological examination has shown no change in the inflammatory cells count of rat oral mucosa. Therefore, it could be concluded that (G) is very promising as a local anesthetic preparation for the treatment of different oral painful conditions.

  9. Controlled release for local delivery of drugs: barriers and models.

    Science.gov (United States)

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Local anesthetics: dentistry's most important drugs, clinical update 2006.

    Science.gov (United States)

    Malamed, Stanley F

    2006-12-01

    Local anesthetics are the safest most effective drugs in medicine for the control and management of pain. They also represent the most important drugs in dentistry. Today, dentistry has a spectrum of local anesthetics that permit pain control to be tailored to the specific needs of the patient: short-, intermediate-, and long-acting drugs. Bupivacaine has become a standard part of the armamentarium for postsurgical pain control while articaine has become the second-most used local anesthetic in the United States since its introduction in 2000. Despite an increase in anecdotal reports of paresthesia since articaine's introduction there is yet, no supporting scientific evidence.

  11. 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.

  12. Chitosan Films: A Potential Local Drug Delivery System for Antibiotics

    OpenAIRE

    Noel, Scott P.; Courtney, Harry; Bumgardner, Joel D.; Warren O. Haggard

    2008-01-01

    Local antibiotic delivery is an emerging area of study designed to provide alternative methods of treatment to clinicians for compromised wound sites where avascular zones can prevent the delivery of antibiotics to the infected tissue. Antibiotic-loaded bone cement is the gold standard for drug-eluting local delivery devices but is not ideal because it requires a removal surgery. Chitosan is a biocompatible, biodegradable polymer that has been used in several different drug delivery applicati...

  13. Drug Usage Evaluation of Dapsone

    Science.gov (United States)

    Kannan, G.; Vasantha, J.; Rani, N. Vanitha; Thennarasu, P.; Kousalya, K.; Anuradha, P.; Reddy, C. Umamaheswara

    2009-01-01

    Dapsone has been the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. It is also widely used by dermatologists in varied skin conditions like dermatitis herpetiformis, bullous pemphigoid, Behcet's disease, lupus erythematous and a host of other skin diseases. Hence an attempt has been made to review the utilization and qualitative evaluation of dapsone over a period of 6 months in a tertiary care teaching hospital. The study consisted of 80 patients (54 leprosy and 26 non-leprosy patients), prescribed with dapsone 100 mg oral once daily. The prescribing patterns of dapsone in leprosy and other dermatological conditions (non-leprosy) were analyzed and the safety, efficacy and appropriateness of the doses prescribed were reviewed. The adverse drug reactions observed in the study population were type I Lepra reactions, gastrointestinal side effects (abdominal pain and anorexia), peripheral neuropathy, other nervous side effects (insomnia, headache and vertigo) and other adverse reactions (fever and tinnitus). Patient information leaflets were distributed to patients to educate on the appropriate use of dapsone. PMID:20502558

  14. 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...

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Felipe González

    Full Text Available 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.

  17. 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.

  18. Accelerated Stability Studies of Three Local Drug Products Prone to ...

    African Journals Online (AJOL)

    Three locally manufactured drug products, Aspirin 300 mg tablets, Chloramphenicol 250 mg capsules and Ampicillin Trihydrate 500 mg capsules, obtained from three production batches, were exposed to storageconditions maintained at 40 °C and 75% relative humidity (RH) in a stability chamber. The products were ...

  19. Multimodal ultrasound mediated drug release model in local cancer therapy.

    Science.gov (United States)

    Myhr, Gunnar

    2007-01-01

    Increased cancer survival rates over the last decades are probably less due to advances of a single treatment modality than to optimization of adjuvant treatment procedures. The efficiency of drug delivery in solid tumours is crucial for achieving local tumour control as cytotoxic agents do not target cancer cells selectively. To enhance tumour uptake and selectivity of drugs, liposomally encapsulated microbubbles with drugs or temperature sensitive liposomes with therapeutics have been suggested as new drug delivery vehicles, in combination with ultrasound or hyperthermia, respectively. The presented release model goes beyond simple drug delivery or traditional adjuvant therapies. It represents targeting, real time monitoring and imaging, and exerts concurrent application of therapeutic modalities, within a multimodal treatment regime, thus enhancing synergism. An appropriate diagnostic tool is applied to determine the region of interest with respect to reference coordinates. The delineated region of interest can be modelled by topographic modelling techniques. A subsequent adequate digital tumour model can facilitate an optimal treatment procedure. The system integrates a diagnostic unit with a therapeutic ultrasonic transmitting component, together with a central processing unit, encompassing algorithms for data processing and visualization. Actual drug uptake is based on passive accumulation of drug carriers. Selective drug release of e.g. cytostatic drugs is achieved by ultrasound induced cavitation well defined to the tumour region. Monitoring of drug release can be achieved by imaging techniques. Measurement and monitoring of cavitational activities within the volume of release, and established functional relationships between cavitation level and drug release, will be bridged to various control functions by the processing unit. Further concurrent thermal treatment approaches and ionizing radiation modi are proposed within the comprehensive treatment model

  20. 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......The article presents various perspectives of drug technology and health care policy in Denmark. Drugs dominate as the most widely used treatment technology in the health care system and the use of drugs is steadily increasing. The pharmaceutical industry's development of drugs is based...... on an economic estimate of developments, expenditures, marketing costs and the anticipated share of the market. Controlled clinical trials have become the main form of documentation required by the health authorities. This method is insufficient to evaluate the (side) effects of the drugs when in actual use...

  1. Evaluation of drug-drug interaction screening software combined with pharmacist intervention.

    Science.gov (United States)

    Moura, Cristiano S; Prado, Nília M; Belo, Najara O; Acurcio, Francisco A

    2012-08-01

    Drug-drug interactions (DDI) in hospitalized patients are highly prevalent and an important source of adverse drug reactions. DI computerized screening system can prevent the occurrence of some of these events. To evaluate the impact of drug-drug interaction (DDI) screening software combined with active intervention in preventing drug interactions. The study was conducted at General Hospital of Vitória da Conquista (HGVC), Brazil. A quasi-experimental study was used to evaluate the impact of IM-Pharma, a locally developed drug-drug interaction screening system, coupled with pharmacist intervention on adverse drug events in the hospital setting. The proportion of patients co-prescribed two interacting drugs were measured in two phases, prior the implementation of IM-Pharma and during the intervention period. DDI rates per 100 patient days were calculated before and after implementation. Risk ratios were estimated by Poisson regression models. A total of 6,834 instances of drug-drug interactions were identified; there was an average of 3.3 DDIs per patient in phase one and 2.5 in phase two, a reduction of 24 % (P = 0.03). There was a 71 % reduction in high-severity drug-drug interaction (P < 0.01). The risk for all DDIs decreased 50 % after the implementation of IM-Pharma (P < 0.01), and for those with high-severity, the reduction was 81 % (P < 0.01). The performance of IM-Pharma combined with pharmacist intervention was positive with an expressive reduction in the risk of DDIs.

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

    African Journals Online (AJOL)

    Cost Evaluation of Commonly Prescribed Antihypertensive Drugs and the Pattern of Prescription among Doctors in the Lagos University Teaching Hospital. ... It was concluded that the prescribing of the new generation drugs i.e. Calcium channel blockers, ACE inhibitors with supposedly little or no metabolic side effects is a ...

  3. 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.

  4. Local Drug Delivery Systems in the Treatment of Periodontitis: A Literature Review.

    Science.gov (United States)

    Da Rocha, Huberth Alexandre Júnior; Silva, Camila Ferreira; Santiago, Fernanda Lopes; Martins, Ludiele Gonçalves; Dias, Pâmella Coelho; De Magalhães, Denildo

    2015-07-01

    In order to complement non-surgical therapy in periodontitis, there are multiple options of antimicrobials, such as metronidazole, chlorhexidine, minocycline, doxycycline and tetracycline, which can be locally delivered into the mucosa. These drugs are used in periodontal pockets and can inhibit or eliminate periodontopathogenic microorganisms as well as modulate the inflammatory response of tissues. However, limited data are available concerning the relationship between effect, efficacy and clinical status of the periodontium. This review aims to evaluate the effect and the efficacy of five types of local drug delivery systems in clinical parameters of periodontology. Researched papers using MEDLINE via PubMed, and LILACS databases related to five types of local drug delivery systems as chlorhexidine gluconate, doxycycline hyclate, metronidazole gel, minocycline ointment and tetracycline fibers, were reviewed aiming to address the mechanism of action and the evidence of clinical effectiveness of adjunctive use of these antimicrobials following surgical and/or non-surgical therapies. Inclusion criteria defined that articles must be randomized controlled trials performed in humans and published between 1996 and 2014. The adjunctive use of local drug delivery systems with controlled release properties may provide a defined, but limited, beneficial response on periodontal pockets. Furthermore, local drug delivery as an active treatment or maintenance therapy depends on clinical findings, responses to treatment described in the literature, desired clinical outcomes, and patients' dental and medical histories, including their past usage of antimicrobials.

  5. Evaluation of pharmacy and therapeutics committee drug evaluation reports.

    Science.gov (United States)

    Majercik, P L; May, J R; Longe, R L; Johnson, M H

    1985-05-01

    Pharmacy and therapeutics (P & T) committee drug evaluation reports prepared by pharmacies and drug information centers (DICs) and product package inserts were compared with standard guidelines to evaluate their quality. Letters were sent to 143 hospital pharmacies asking them to submit a previously prepared drug evaluation report on temazepam, moxalactam disodium, or atenolol. The reports and package inserts for these three drugs were evaluated by the presence of 40 elements derived from the published ASHP guidelines for drug evaluation report preparation. Responses were obtained from 124 (87%) pharmacies; however, only 80 reports (60 DIC-prepared and 20 pharmacy-prepared) were received. The reports contained a mean of 28 of the 40 (70%) possible elements. The most frequently omitted elements were AHFS number, potential unlabeled uses, drug-drug interactions, drug-disease-laboratory test interactions, risk and benefit data, prevention and treatment of side effects, comparisons with established treatment, and disadvantages of the drug under consideration. Although the reports prepared by the DICs and pharmacies contained the same amount of information, the DIC-prepared reports included data more frequently on supply sources, therapeutic indications, approved labeling, comparison with established treatment, bioavailability and pharmacokinetics, and recommendations. Most of the reports contained more elements than the corresponding package inserts. The product package inserts did not contain the comparative elements required for P & T committee decisions. Both the pharmacy- and DIC-prepared reports failed to contain all 40 elements recommended in the standard guidelines, suggesting the need for more thorough reports.

  6. 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.

  7. 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

  8. 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.

  9. Economic evaluation in collaborative hospital drug evaluation reports

    Directory of Open Access Journals (Sweden)

    Ana Ortega

    2015-09-01

    Full Text Available Objective: economic evaluation is a fundamental criterion when deciding a drug’s place in therapy. The MADRE method (Method for Assistance in making Decisions and Writing Drug Evaluation Reports is widely used for drug evaluation. This method was developed by the GENESIS group of the Spanish Society of Hospital Pharmacy (SEFH, including economic evaluation. We intend to improve the economic aspects of this method. As for the direction to take, we have to first analyze our previous experiences with the current methodology and propose necessary improvements. Method: economic evaluation sections in collaboratively conducted drug evaluation reports (as the scientific society, SEFH with the MADRE method were reviewed retrospectively. Results: thirty-two reports were reviewed, 87.5% of them included an economic evaluation conducted by authors and 65.6% contained published economic evaluations. In 90.6% of the reports, a Budget impact analysis was conducted. The cost per life year gained or per Quality Adjusted Life Year gained was present in 14 reports. Twenty-three reports received public comments regarding the need to improve the economic aspect. Main difficulties: low quality evidence in the target population, no comparative studies with a relevant comparator, non-final outcomes evaluated, no quality of life data, no fixed drug price available, dosing uncertainty, and different prices for the same drug. Conclusions: proposed improvements: incorporating different forms of aid for non-drug costs, survival estimation and adapting published economic evaluations; establishing criteria for drug price selection, decision-making in conditions of uncertainty and poor quality evidence, dose calculation and cost-effectiveness thresholds depending on different situations.

  10. Nanomaterials for the Local and Targeted Delivery of Osteoarthritis Drugs

    Directory of Open Access Journals (Sweden)

    Parthiban Chinnagounder Periyasamy

    2012-01-01

    Full Text Available Nanotechnology 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 macrosystems for specific applications. Although the debate regarding the safety of synthetic nanomaterials 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 nanoscale 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 nanotechnological formulations. We describe the different nanodrug delivery systems and their potential for cartilage repair. This paper provides the reader basal understanding of nanomaterials and aims at drawing new perspectives on the use of existing nanotechnological formulations for the treatment of osteoarthritis.

  11. 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.

  12. Evaluation of drug interactions with nanofibrillar cellulose.

    Science.gov (United States)

    Kolakovic, Ruzica; Peltonen, Leena; Laukkanen, Antti; Hellman, Maarit; Laaksonen, Päivi; Linder, Markus B; Hirvonen, Jouni; Laaksonen, Timo

    2013-11-01

    Nanofibrillar cellulose (NFC) (also referred to as cellulose nanofibers, nanocellulose, microfibrillated, or nanofibrillated cellulose) has recently gotten wide attention in various research areas and it has also been studied as excipient in formulation of the pharmaceutical dosage forms. Here, we have evaluated the interactions between NFC and the model drugs of different structural characteristics (size, charge, etc.). The series of permeation studies were utilized to evaluate the ability of the drugs in solution to diffuse through the thin, porous, dry NFC films. An incubation method was used to determine capacity of binding of chosen model drugs to NFC as well as isothermal titration calorimetry (ITC) to study thermodynamics of the binding process. A genetically engineered fusion protein carrying double cellulose binding domain was used as a positive control since its affinity and capacity of binding for NFC have already been reported. The permeation studies revealed the size dependent diffusion rate of the model drugs through the NFC films. The results of both binding and ITC studies showed that the studied drugs bind to the NFC material and indicated the pH dependence of the binding and electrostatic forces as the main mechanism. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Evaluation of a Flipped Drug Literature Evaluation Course.

    Science.gov (United States)

    Giuliano, Christopher Alan; Moser, Lynette R

    2016-05-25

    Objective. To evaluate a flipped drug literature evaluation course for first-year pharmacy students. Design. A drug literature evaluation course was flipped during the 2014 winter semester. Homework from 2013 was transformed into activities and lectures were transformed into multiple short YouTube videos. Assessment. Average examination scores increased from 75.6% to 86.1%. Eighty-two of 94 students completed the postcourse survey in 2014. Compared to traditional lecture, 59.8% of students indicated they preferred the flipped course. Additionally, students felt the course was important, the in-class activities were helpful, and some of the YouTube videos could be improved. We found length of the video to be significantly correlated with the percentage of videos viewed. Conclusion. The flipped model should be considered in drug literature evaluation courses that seek to increase the amount of active learning in the classroom.

  14. [Drug evaluation: new requirements and perspectives].

    Science.gov (United States)

    Addis, Antonio; Rocchi, Francesca

    2006-11-01

    Lately the European and international regulatory Agencies, responsible for the evaluation of drugs, have not been capable to implement regulatory processes guiding clinical practice efficiently. The sudden withdrawal of innovative drugs, the incapacity of assuring independence, the not controlled trend of pharmaceutical expenditure are signals of the failure of a system which should respond to the mandate of public health and market regulation. Some intrinsic limits of present regulatory systems arise because regulatory Agencies approve medicinal products on the basis of minimum standards of efficacy or owing to fast registration procedures which do not allow to assure the real efficacy and safety of the product approved. Non-inferiority and equivalence trials, short duration studies conducted on small populations (not representing the real setting of utilization in clinical practice) are often considered sufficient for drug registration. Moreover, Agencies often lack data on the safety of approved products and based on post-marketing surveillance and monitoring plans which can assure the real profile of drug safety. Owing to the institution of the Italian Medicines Agency (AIFA), Italy has lately approached European standards of regulation and proposed a new original regulatory approach attempting to go beyond some of the main limitations described above. The main points the model is based on are: promotion of use appropriateness through the analysis of experiences occurring in the area; promotion of independent drug research in order to collect data reliable and useful for drug regulation; publication and distribution of independent information on drug utilization for health professionals. The Italian approach tries to bring regulatory provisions close to clinical practice by promoting a correct and rational use of drugs and developing new areas of intervention for research, vigilance and information.

  15. Controlled Release System for Localized and Sustained Drug Delivery Applications

    Science.gov (United States)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  16. Drug-coated microneedles for rapid and painless local anesthesia.

    Science.gov (United States)

    Baek, Sung-Hyun; Shin, Ju-Hyung; Kim, Yeu-Chun

    2017-03-01

    This study showed that drug-coated PLLA (Poly (L-lactide)) microneedle arrays can induce rapid and painless local anesthesia. Microneedle arrays were fabricated using a micro-molding technique, and the needle tips were coated with 290.6 ± 45.9 μg of lidocaine, the most widely used local anesthetic worldwide. A dip-coating device was newly designed for the coating step using an optimized coating formulation. Lidocaine coated on the arrays was released rapidly into PBS within 2 min, and its stability in storage lasted 3 weeks at 4, 25, and 37°C. Furthermore, the microneedle arrays showed consistent in vitro skin penetration and delivered 200.8 ± 43.9, 224.2 ± 39.3, and 244.1 ± 19.6 μg of lidocaine into the skin 1, 2, and 5 min after application with a high delivery efficiency of 69, 77, and 84%. Compared to a commercially available topical anesthetic EMLA® cream, a 22.0, 13.6, and 14.0-fold higher amount of lidocaine was delivered into the skin. Note, in vitro skin permeation of Lidocaine was also notably enhanced by a 2-min-application of the lidocaine-coated microneedle arrays. Altogether, these results suggest that the biocompatible lidocaine-coated PLLA microneedle arrays could provide significantly rapid local anesthesia in a painless manner without any of the issues from topical applications or hypodermic injections of local anesthetics.

  17. 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.

  18. Polymeric particles for sustained and local drug delivery

    NARCIS (Netherlands)

    Ramazani, F.

    2015-01-01

    Controlled drug delivery systems have been extensively investigated as means to prolong the action of drugs in the body. In this regard, a drug is incorporated into a carrier (e.g., polymeric material) in such a way that the drug is released from the matrix in a controlled manner for an extended

  19. 76 FR 60505 - Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop...

    Science.gov (United States)

    2011-09-29

    ... HUMAN SERVICES Food and Drug Administration Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is opening a comment period for the...

  20. 76 FR 45268 - Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop

    Science.gov (United States)

    2011-07-28

    ... HUMAN SERVICES Food and Drug Administration Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug Administration (FDA) is announcing a public workshop regarding the...

  1. Dentists' perceptions of a new local anaesthetic drug--articaine.

    Science.gov (United States)

    Yapp, K E; Hopcraft, M S; Parashos, P

    2012-03-01

    Articaine is a new local anaesthetic drug introduced to the Australian dental market. The aim of this study was to elicit information regarding the use of articaine in Australia, and factors that influence attitudes towards adoption of new technology. A self-administered postal questionnaire was sent to a stratified systematic sample of dentists who were members of the Australian Dental Association, with questions regarding details about articaine use and how influences such as education and scientific literature affect their adoption of new technology. Of the sample, 53% responded and over 70% of dentists surveyed used articaine, with 95% and 97% of respondents identifying scientific literature and continuing professional development courses respectively as influencing factors in their adoption of new technology. The most common reason for not using articaine was no perceived advantage and the most influential factor that would encourage non-users to start using articaine was a scientifically proven advantage. Senior clinicians, specialists and public sector dentists were less likely to use articaine. A majority of Australian dentists were using articaine and cited continuing professional development courses, scientific literature and anecdotal peer reports as being influential in their adoption of new technology. © 2012 Australian Dental Association.

  2. A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release

    Science.gov (United States)

    Liu, Heng; Fu, Yike; Li, Yangyang; Ren, Zhaohui; Li, Xiang; Han, Gaorong; Mao, Chuanbin

    2016-01-01

    Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb3+/Er3+ codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy. PMID:27557281

  3. drug use evaluation on cotrimoxazole preventive therapy for people

    African Journals Online (AJOL)

    user

    BACKGROUND: Drug use evaluation is a performance improvement method that focuses on evaluation and improvement of drug use ... KEY WORDS: drug use evaluation, cotrimoxazole, HIV/AIDS, Jimma, Ethiopia. INTRODUCTION .... female was pregnant but the pregnancy history of 11. (35.5%) females was not ...

  4. Evaluation of two closed-system drug transfer device in the antineoplastic drug elaboration process

    Directory of Open Access Journals (Sweden)

    Sandra Gómez-Álvarez

    2016-01-01

    Full Text Available Objective: 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. Method: 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. Results: 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. Conclusions: 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

  5. Evaluation of theophylline therapeutic drug monitoring service

    Directory of Open Access Journals (Sweden)

    Neža Rugelj

    2015-05-01

    Full Text Available BackgroundTherapeutic monitoring of theophylline serum levels is required due to its narrow therapeutic range and marked interindividual pharmacokinetic variability. We evaluated therapeutic drug monitoring service for theophylline in Slovenian clinical setting, which currently includes no pharmacokinetic evaluation of measured theophylline serum concentrations. MethodsWe  retrospectively evaluated 127 randomly selected theophylline serum level determinations performed in 2010 in a tertiary clinical setting in Slovenia. Demographic data, information on theophylline dosing and blood sampling was collected from patients’ data files. Authors evaluated the appropriateness of the following procedures: indications for theophylline serum concentration measurement, timing of blood sampling and dosage adjustments made after theophylline levels had been reported. On the basis of collected data, population pharmacokinetic model for theophylline was built and further used for the evaluation of dosage adjustments. ResultsOut of 127 cases, 107 (84.3% had clinically justified indication for theophylline serum level measurement. Near half of measurements (44.9% were performed before the steady state of theophylline concentrations was established. 65% of measured concentrations were subtherapeutic and the average measured concentration was below therapeutic range (53.1 μmol/L. Despite subtherapeutic concentrations the dose of theophylline was mainly not increased. Pharmacokinetic model enabled the calculation of average optimal daily dose which was significantly higher than the average actual daily dose used (876 mg vs. 572 mg, p < 0.001. ConclusionsTheophylline TDM service should be optimized and pharmacokinetic interpretation of theophylline serum levels should be integrated into clinical practice.

  6. 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...

  7. Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.

    Science.gov (United States)

    Adams, Wallace P; Ahrens, Richard C; Chen, Mei-Ling; Christopher, David; Chowdhury, Badrul A; Conner, Dale P; Dalby, Richard; Fitzgerald, Kevin; Hendeles, Leslie; Hickey, Anthony J; Hochhaus, Günther; Laube, Beth L; Lucas, Paul; Lee, Sau L; Lyapustina, Svetlana; Li, Bing; O'Connor, Dennis; Parikh, Neil; Parkins, David A; Peri, Prasad; Pitcairn, Gary R; Riebe, Michael; Roy, Partha; Shah, Tushar; Singh, Gur Jai Pal; Sharp, Sandra Suarez; Suman, Julie D; Weda, Marjolein; Woodcock, Janet; Yu, Lawrence

    2010-02-01

    endpoints) with a sufficiently steep dose-response need to be identified and validated for all relevant drug classes; and (5) the utility of pharmacokinetic studies for evaluating "local pulmonary delivery" equivalence deserves more attention. A summary of action items for seminars and working groups to address these topics in the future is also presented.

  8. Evaluation of two closed-system drug transfer device in the antineoplastic drug elaboration process

    National Research Council Canada - National Science Library

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

    2016-01-01

    Objective: 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. Method...

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

    Science.gov (United States)

    Mayati, Abdullah; Moreau, Amélie; Le Vée, Marc; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Fardel, Olivier

    2017-01-01

    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. PMID:28375174

  10. Evaluation Results From Prospective Drug Utilization Review: Medicaid Demonstrations

    OpenAIRE

    Kidder, David; Bae, Jay

    1999-01-01

    In 1992 HCFA awarded two cooperative agreements for demonstrations of prospective drug utilization review (PDUR). Iowa tested an on-line prospective drug utilization review (OPDUR) system. Washington tested payments to pharmacists for providing non-dispensing “cognitive services” (CS). In this article the authors report on an evaluation of these demonstrations and on three assessments of retrospective drug utilization review (RDUR) interventions. The evaluation failed to detect effects of eit...

  11. DRUG MARKET RECONSTITUTION AFTER HURRICANE KATRINA: LESSONS FOR LOCAL DRUG ABUSE CONTROL INITIATIVES.

    Science.gov (United States)

    Bennett, Alex S; Golub, Andrew; Dunlap, Eloise

    2011-01-01

    Hurricane Katrina accomplished what no law enforcement initiative could ever achieve: It completely eradicated the New Orleans drug market. However, Katrina did little to eliminate the demand for drugs. This article documents the process of the drug market reconstitution that occurred 2005-2008 based on in-depth interviews and focus groups with predominately low-income drug users and sellers. Before Katrina, the drug market was largely characterized by socially-bonded participants involved with corporate style distribution. After Katrina, a violent freelance market emerged. The conclusion draws recommendations for law enforcement for dealing with drug markets after a major disaster.This article uses New Orleans as a case study to chart the process of drug market reconstitution following an extreme disaster, namely Hurricane Katrina. On August 29, 2005, Hurricane Katrina made landfall and engulfed the New Orleans area, overwhelming levees and causing extensive flooding and destruction across the city. The storm generated 30- to 40-foot waves, which demolished many cities and small towns in Southern Mississippi and Alabama and caused considerable wind damage further inland. Although the hurricane eye missed central New Orleans by about 30 miles, the wave action in Lake Pontchartrain caused several levees to break and flood most of eastern New Orleans, which was under sea level. The storm had an impact on practically all New Orleans residents and almost destroyed New Orleans (Cooper & Block, 2006; Levitt & Whitaker, 2009; Lee, 2006).Our research focused on the impact of this storm on the drug markets in New Orleans. Katrina destroyed the physical environment and organizational structure that sustained the drug trade, yet drug use and sales did not disappear. During and soon after the storm, improvised sales and distribution organizations provided a wide range of illicit drugs to users (see Dunlap, Johnson, Kotarba, & Fackler, 2009; Dunlap & Golub, 2010; Dunlap

  12. Building the evaluation capacity of California's local tobacco control programs.

    Science.gov (United States)

    Treiber, Jeanette; Cassady, Diana; Kipke, Robin; Kwon, Nicole; Satterlund, Travis

    2011-11-01

    Successful evaluation capacity building requires a dynamic balance between responding to local agency needs and ensuring that local staff have appropriate skills to conduct rigorous evaluations. In 2004, the California Tobacco Control Program established the Tobacco Control Evaluation Center (TCEC), based at a public research university, to provide evaluation technical assistance to approximately 100 local agencies implementing tobacco control programs. TCEC has been responsive to local needs, for instance, by answering 512 technical assistance requests in the first 5 years of operation and by tailoring training according to needs assessment results. About 50% of the technical assistance requests were for new data collection instruments (n = 255). TCEC has sought proactively to improve local evaluation skills, most recently in a data analysis and report writing skill building campaign that included a webinar, newsletter, and seven regional training meetings. Preliminary analysis suggests a 20% improvement in scores for the local final evaluation reports as a result of this campaign. It is concluded that evaluation technical assistance can be provided effectively by a university as long as the local context is kept in mind, and a balance of responsive and proactive technical assistance is provided.

  13. Good quality locally procured drugs can be as effective as internationally quality assured drugs in treating multi-drug resistant tuberculosis.

    Science.gov (United States)

    Qadeer, Ejaz; Fatima, Razia; Fielding, Katherine; Qazi, Fahad; Moore, David; Khan, Mishal S

    2015-01-01

    Owing toGiven the high costs of drugs to treat multi-drug resistant tuberculosis (MDR-TB), the Green Light Committee (GLC) initiative enables TB programs to procure quality-assured drugs at reduced prices. Despite price reductions, internationally quality assured (IQA) drugs can be more expensive than locally procured drugs. There is little evidence to inform decision-makers about whether IQA drugs are more effective than local drugs. This is the first study to compare outcomes between MDR-TB patients treated using IQA, and locally procured drugs in the same hospitals during the same time period. A retrospective cohort study was conducted in three hospitals across Pakistan. Data on baseline characteristics and treatment outcomes during the first six months of treatment were extracted from hospital records of adult culture-positive pulmonary MDR-TB patients starting treatment between January 2011 and June 2012. Two cohorts were defined: patients receiving IQA drugs, and patients receiving locally procured non-IQA drugs. Data were analysed using Kaplan-Meier curves and Cox proportional hazards regression. The primary outcome compared between cohorts was time to culture conversion. Of 231 patients, 90 were in the IQA and 141 in the non-IQA cohorts. Baseline characteristics were similar except for higher frequency of quinolone resistance in the IQA cohort. Overall, 193 patients (84%) culture converted. Culture conversion was not faster in the IQA cohort; the median time was 81 and 68 days in the IQA and non-IQA cohorts, respectively. Unadjusted and adjusted hazard ratios for culture conversion in IQA verses non-IQA cohorts were 0.82 (95%-CI, 0.62-1.10) and 0.95 (95%-CI, 0.66-1.36) respectively. Use of good quality, locally procured drugs can be effective in treating MDR-TB, may involve lower costs than using IQA drugs and could strengthen developing country drug quality assurance systems. This may be a suitable alternative in lieu of or whilst awaiting arrival of

  14. 122 evaluation of the quality of locally manufactured antimicrobial ...

    African Journals Online (AJOL)

    ABSTRACT. Locally manufactured antimicrobial susceptibility discs are becoming increasingly used in both private and government hospital laboratories in Nigeria. Data on the quality of these locally manufactured antimicrobial discs are not available. In order to provide some data, we evaluated the quality of three brands ...

  15. 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, ...

  16. Modulated evaluation metrics for drug-based ontologies.

    Science.gov (United States)

    Amith, Muhammad; Tao, Cui

    2017-04-24

    Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation.

  17. Localization in wireless sensor networks: Classification and evaluation of techniques

    National Research Council Canada - National Science Library

    Ewa Niewiadomska-Szynkiewicz

    2012-01-01

      Localization in wireless sensor networks: Classification and evaluation of techniques Recent advances in technology have enabled the development of low cost, low power and multi functional wireless sensing devices...

  18. Consensus Recommendations for Systematic Evaluation of Drug-Drug Interaction Evidence for Clinical Decision Support

    Science.gov (United States)

    Scheife, Richard T.; Hines, Lisa E.; Boyce, Richard D.; Chung, Sophie P.; Momper, Jeremiah; Sommer, Christine D.; Abernethy, Darrell R.; Horn, John; Sklar, Stephen J.; Wong, Samantha K.; Jones, Gretchen; Brown, Mary; Grizzle, Amy J.; Comes, Susan; Wilkins, Tricia Lee; Borst, Clarissa; Wittie, Michael A.; Rich, Alissa; Malone, Daniel C.

    2015-01-01

    Background Healthcare organizations, compendia, and drug knowledgebase vendors use varying methods to evaluate and synthesize evidence on drug-drug interactions (DDIs). This situation has a negative effect on electronic prescribing and medication information systems that warn clinicians of potentially harmful medication combinations. Objective To provide recommendations for systematic evaluation of evidence from the scientific literature, drug product labeling, and regulatory documents with respect to DDIs for clinical decision support. Methods A conference series was conducted to develop a structured process to improve the quality of DDI alerting systems. Three expert workgroups were assembled to address the goals of the conference. The Evidence Workgroup consisted of 15 individuals with expertise in pharmacology, drug information, biomedical informatics, and clinical decision support. Workgroup members met via webinar from January 2013 to February 2014. Two in-person meetings were conducted in May and September 2013 to reach consensus on recommendations. Results We developed expert-consensus answers to three key questions: 1) What is the best approach to evaluate DDI evidence?; 2) What evidence is required for a DDI to be applicable to an entire class of drugs?; and 3) How should a structured evaluation process be vetted and validated? Conclusion Evidence-based decision support for DDIs requires consistent application of transparent and systematic methods to evaluate the evidence. Drug information systems that implement these recommendations should be able to provide higher quality information about DDIs in drug compendia and clinical decision support tools. PMID:25556085

  19. Need for multicriteria evaluation of generic drug policies.

    Science.gov (United States)

    Kaló, Zoltán; Holtorf, Anke-Peggy; Alfonso-Cristancho, Rafael; Shen, Jie; Ágh, Tamás; Inotai, András; Brixner, Diana

    2015-03-01

    Policymakers tend to focus on improving patented drug policies because they are under pressure from patients, physicians, and manufacturers to increase access to novel therapies. The success of pharmaceutical innovation over the last few decades has led to the availability of many off-patent drugs to treat disease areas with the greatest public health need. Therefore, the success of public health programs in improving the health status of the total population is highly dependent on the efficiency of generic drug policies. The objective of this article was to explore factors influencing the true efficiency of generic prescription drug policies in supporting public health initiatives in the developed world. Health care decision makers often assess the efficiency of generic drug policies by the level of price erosion and market share of generics. Drug quality, bioequivalence, in some cases drug formulations, supply reliability, medical adherence and persistence, health outcomes, and nondrug costs, however, are also attributes of success for generic drug policies. Further methodological research is needed to measure and improve the efficiency of generic drug policies. This also requires extension of the evidence base of the impact of generic drugs, partly based on real-world evidence. Multicriteria decision analysis may assist policymakers and researchers to evaluate the true value of generic drugs. Copyright © 2015. Published by Elsevier Inc.

  20. Surgical suture assembled with polymeric drug-delivery sheet for sustained, local pain relief.

    Science.gov (United States)

    Lee, Ji Eun; Park, Subin; Park, Min; Kim, Myung Hun; Park, Chun Gwon; Lee, Seung Ho; Choi, Sung Yoon; Kim, Byung Hwi; Park, Hyo Jin; Park, Ji-Ho; Heo, Chan Yeong; Choy, Young Bin

    2013-09-01

    Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical strength of the suture itself - strength that is essential for successful wound closure. Thus, it is not easy to control drug delivery with sutures, and the drug-delivery surgical sutures available for clinical use are now limited to anti-infection roles. Here, we demonstrate a surgical suture enabled to provide controlled delivery of a pain-relief drug and, more importantly, we demonstrate how it can be fabricated to maintain the mechanical strength of the suture itself. For this purpose, we separately prepare a drug-delivery sheet composed of a biocompatible polymer and a pain-relief drug, which is then physically assembled with a type of surgical suture that is already in clinical use. In this way, the drug release profiles can be tailored for the period of therapeutic need by modifying only the drug-loaded polymer sheet without adversely influencing the mechanical strength of the suture. The drug-delivery sutures in this work can effectively relieve the pain at the surgical site in a sustained manner during the period of wound healing, while showing biocompatibility and mechanical properties comparable to those of the original surgical suture in clinical use. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Magnetic luminescent porous silicon microparticles for localized delivery of molecular drug payloads.

    Science.gov (United States)

    Gu, Luo; Park, Ji-Ho; Duong, Kim H; Ruoslahti, Erkki; Sailor, Michael J

    2010-11-22

    Magnetic manipulation, fluorescent tracking, and localized delivery of a drug payload to cancer cells in vitro is demonstrated, using nanostructured porous silicon microparticles as a carrier. The multifunctional microparticles are prepared by electrochemical porosification of a silicon wafer in a hydrofluoric acid-containing electrolyte, followed by removal and fracture of the porous layer into particles using ultrasound. The intrinsically luminescent particles are loaded with superparamagnetic iron oxide nanoparticles and the anti-cancer drug doxorubicin. The drug-containing particles are delivered to human cervical cancer (HeLa) cells in vitro, under the guidance of a magnetic field. The high concentration of particles in the proximity of the magnetic field results in a high concentration of drug being released in that region of the Petri dish, and localized cell death is confirmed by cellular viability assay (Calcein AM).

  2. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    Science.gov (United States)

    Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

    2014-07-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

  3. Advanced drug delivery systems for local treatment of the oral cavity.

    Science.gov (United States)

    Nguyen, Sanko; Hiorth, Marianne

    2015-01-01

    Good oral health is of major importance for general health and well-being. Several innovative drug delivery systems have been developed for the local treatment and prevention of various diseases in the oral cavity. However, there are currently few optimal systems and many therapeutic challenges still remain, including low drug efficacy and retention at targeted site of action. The present review provides an insight into the latest drug delivery strategies for the local treatment and prevention of the four most common oral pathologies, namely, dental caries, periodontitis, oral mucosal infections and oral cancer. The potential of bioadhesive formulations, nanoparticulate platforms, multifunctional systems and photodynamic methodologies to improve therapy and prophylaxis in future local applications for the oral cavity will be discussed.

  4. In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

    Directory of Open Access Journals (Sweden)

    Karin Goebel

    2013-06-01

    Full Text Available In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.

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

    African Journals Online (AJOL)

    2017-10-26

    Oct 26, 2017 ... Demographic details, brand/ generic name, indication, route, dosage, frequency ... KEYWORDS: Airway, pharmaco-epidemiology, pharmacy, public health, survey. Evaluation of Drug Utilization Pattern for Patients .... also found a low overall awareness level regarding national guidelines among physicians.

  6. Finite element modelling of the canine and feline outer ear canal: benefits for local drug delivery?

    Science.gov (United States)

    Wefstaedt, Patrick; Behrens, Bernd-Arno; Nolte, Ingo; Bouguecha, Anas

    2011-01-01

    Current therapeutic regimes of outer ear infections in dogs and cats aim at the application of efficient local therapeutics after cleaning of the acoustic meatus. One so far insufficiently answered question is if the local application of these substances results in an individually suitable drug concentration in the external ear canal. Thus, the purpose of the present study was to develop a finite element model to calculate the values of the different areas of the external acoustic meatus in dogs and cats in order to provide a tool for the benefit of an appropriate local drug dosage determination. A 3D finite element model (FEM), based on computer tomographic (CT) data sets of four dogs and two cats, was generated to determine areas and volumes of the outer ear canal. Furthermore, various ear therapeutics and cleansers were tested concerning their optimal distribution on 5 cm2 dog and cat skin. The data shows major variations of the area values of the external auditory canal in case of the different dogs but not in the examined cats. These results suggest that manufacturer's recommendations of the pharmaceuticals might be insufficient in terms of achieving an optimal drug concentration in the outer ear canal especially in larger dogs. In conclusion, the developed finite element model has shown to be suitable to calculate areas of the outer ear canal in cats and dogs and could be of help in context with the definition of optimal drug concentrations for a local drug delivery.

  7. 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.

  8. 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.

  9. Adapting the Locales Framework for Heuristic Evaluation of Groupware

    Directory of Open Access Journals (Sweden)

    Saul Greenberg

    2000-05-01

    Full Text Available Heuristic evaluation is a rapid, cheap and effective way for identifying usability problems in single user systems. However, current heuristics do not provide guidance for discovering problems specific to groupware usability. In this paper, we take the Locales Framework and restate it as heuristics appropriate for evaluating groupware. These are: 1 Provide locales; 2 Provide awareness within locales; 3 Allow individual views; 4 Allow people to manage and stay aware of their evolving interactions; and 5 Provide a way to organize and relate locales to one another. To see if these new heuristics are useful in practice, we used them to inspect the interface of Teamwave Workplace, a commercial groupware product. We were successful in identifying the strengths of Teamwave as well as both major and minor interface problems.

  10. Evaluating local food programs: the case of Select Nova Scotia.

    Science.gov (United States)

    Knight, Andrew J

    2013-02-01

    This study evaluated the effectiveness of the buy local food program Select Nova Scotia; a government program with the goal to increase awareness and consumption of Nova Scotia produced and processed agri-food products by Nova Scotians and visitors. The evaluation methodology was based on prior evaluation resources and local food consumer research. Data were gathered through a web panel survey; 877 respondents completed the survey in June 2010. The results suggest that the program is reaching a wider audience than just those predisposed to local food initiatives. In addition, awareness of Select Nova was related to perceptions of local benefits and barriers, as well as purchase motivation and behavior. Respondents who were aware of Select Nova Scotia rated societal benefits as more important and viewed location and price as less of a barrier; they were also more likely to be highly motivated to purchase local foods. This study also informs results found in previous consumer research studies and identifies marketing opportunities to enhance the effectiveness of local food programs. The results suggest that societal benefits might be used as a way to differentiate products with similar attributes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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 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.

  13. 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.)

  14. 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.

  15. Injectable hydrogel based on quaternized chitosan, gelatin and dopamine as localized drug delivery system to treat Parkinson's disease.

    Science.gov (United States)

    Ren, Yizhuo; Zhao, Xin; Liang, Xiaofeng; Ma, Peter X; Guo, Baolin

    2017-12-01

    There is still an enormous demand for designing materials to the treatment of Parkinson's disease, and dopamine-based injectable polysaccharide hydrogels as localized drug delivery system have huge potential. Here, we developed a facile approach to prepare dopamine-based and polydopamine crosslinked injectable hydrogels by simply oxidizing a mixture of quaternized chitosan, gelatin and dopamine under physiological conditions. These injectable hydrogels showed stable mechanical strength by rheometer and exhibited good degradability evaluated by in vitro degradation test. The chemical structure and morphology of the hydrogels were characterized by FT-IR and SEM. Dopamine as a drug for treating Parkinson's disease and metronidazole as an anti-inflammatory drug were encapsulated in the hydrogel. The release profiles indicated that the injectable hydrogels have great capacity as a carrier for long-term localized release system for dopamine and metronidazole. Furthermore, the cytocompatibility of the hydrogels was confirmed by cell viability and proliferation assays using mouse L929 fibroblast cells. This work provides a new and facile approach to prepare dopamine-based injectable materials which can be used as long-term injectable sustained release system for dopamine as well as anti-inflammatory drug for Parkinson's treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. 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…

  17. Evaluation of Drug Prescriptions in Oral Surgery | Ehigiator ...

    African Journals Online (AJOL)

    Evaluation of Drug Prescriptions in Oral Surgery. ... To evaluate the pattern of medication prescription in an oral surgery outpatient clinic. A questionnaire was distributed to Resident doctord ... This however buttresses that the management of the orofacial pain and dental infection is inherent in dental practice. Keywords: Drig ...

  18. Evaluation of an exotic maize population adapted to a locality.

    Science.gov (United States)

    Hanson, W D; Johnson, E C

    1981-01-01

    An exotic Zea mays L. population ('Tuxpeno') was adapted to North Carolina conditions by first introducing genes for adaptability from two North Carolina varieties ([('Jarvis' X 'Indian Chief')'Tuxpeno']'Tuxpeno') including four generations of intermating, and then selecting for adaptability using maturity as the primary measure. The study evaluated selection for adaptability and the diversity available between adapted 'Tuxpeno' and the local varieties, 'Jarvis' and 'Indian Chief'. Analytical procedures were developed to quantify the diversity between populations and the complementation of local varieties by introduced germ plasms. The analyses utilized the specific effects available from the diallel mating design.Three replicate selections responded similarly under simple recurrent mass selection (1/10) for the earliest disease-free plants initially and additionally for plant types (primarily height) in the final generation. The 1/4 local germ plasm permitted rapid adaptation of 'Tuxpeno' gene pool to local conditions. The adapted 'Tuxpeno' populations yielded similarly to the local populations with an average heterosis for grain yield of 28% when crossed to the local populations used as source of genes for adaptability. The diversity found between adapted 'Tuxpeno' lines and these local varieties based on genes affecting grain yield was 1.5 to 2.5 times that measured between the local varieties ('Jarvis' and 'Indian Chief'). Diversity lost through intergradation with local material was a reasonable investment. Yield genes introduced from 'Tuxpeno' complemented local gene pools through nonadditive, primarily dominance-associated, gene effects. Reassortment of major gene blocks apparently occurred leading to significant divergence among replicate selections involving both additive-associated and dominance-associated gene effects.

  19. 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.

  20. Ultrasound Strain Measurements for Evaluating Local Pulmonary Ventilation

    Science.gov (United States)

    Rubin, Jonathan M.; Horowitz, Jeffrey C.; Sisson, Thomas H.; Kim, Kang; Ortiz, Luis A.; Hamilton, James D.

    2015-01-01

    Local lung function is difficult to evaluate, because most lung function estimates are either global in nature, e.g. pulmonary function tests, or require equipment that cannot be used at a patient's bedside, such as computed tomograms. Yet, local function measurements would be highly desirable for many reasons. In a recent publication [1], we were able to track displacements of the lung surface during breathing. We have now extended these results to measuring lung strains during respiration as a means of assessing local lung ventilation. We studied two normal human volunteers and 12 mice with either normal lung function or experimentally induced pulmonary fibrosis. The difference in strains between the control, normal mice and those with pulmonary fibrosis was significant (p < 0.02), while the strains measured in the human volunteers closely matched linear strains predicted from the literature. Ultrasonography may be able to assess local lung ventilation. PMID:26635917

  1. Formulation and evaluation of floating drug delivery system of famotidine.

    Science.gov (United States)

    Satishbabu, B K; Sandeep, V R; Ravi, R B; Shrutinag, R

    2010-11-01

    A multiple unit oral floating drug delivery system of famotidine was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. Drug and polymer compatibility was studied by subjecting physical mixtures of drug and polymers to differential scanning calorimetry. Cod liver oil entrapped calcium alginate beads containing famotidine, capable of floating in the gastric condition were formulated and evaluated. The gel beads were prepared by emulsion gelation method by employing sodium alginate alone and mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of selected factors, such as percentage of oil and amount of copolymers on floating properties was investigated. The beads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug release study of the beads was carried out in simulated gastric media employing a modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified by incorporating a water jacket to the apparatus to circulate hot water to maintain 37±2° for throughout the release study. All the oil entrapped calcium alginate beads floated if a sufficient amount of oil was used. Beads formulated employing sodium alginate alone could not sustain the drug release up to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers demonstrated sustained release of famotidine up to 8 h. The results suggested that cod liver oil entrapped calcium alginate beads were promising as a carrier for intragastric floating drug delivery of famotidine.

  2. Evaluation of parasitic contamination from local sources of drinking ...

    African Journals Online (AJOL)

    Water-borne parasitic infections have become a source of concern in recent times due to the contamination of various drinking-water sources. A survey on the parasitic contamination of drinking-water sources was carried out in Ezza North Local Government Area of Ebonyi State, south-east Nigeria. This is to evaluate the ...

  3. Performance Evaluation of Refractory Bricks produced from locally ...

    African Journals Online (AJOL)

    The performance evaluation of refractory bricks produced from some local clay deposits in Delta State, Nigeria was investigated. Four major sites in Delta State renowned for abundant clay deposits were selected, namely; Oghara, Ekpan, Ubeji and Jeddo. The clay samples were crushed, milled (pulverised) and sieved to ...

  4. Evaluation of three diets formulated from local agroindustrial by ...

    African Journals Online (AJOL)

    Three diets were evaluated for growth, production and economic performance of the Nile tilapia, Oreochromis niloticus, after a culture period of 160 days at the Aquaculture Research and Development Centre (ARDEC), Akosombo, Ghana. Locally available agro-industrial by-products were used to compound the diets.

  5. 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.

  6. Evaluation phytosanitaire de varietes locales et de nouvelles ...

    African Journals Online (AJOL)

    In the frame of the adaptability study of 20 tomato varieties to the West African ecological conditions; the phytosanitary behavior of these varieties was accessed in the comparison with 2 local varieties. The major pests identified on the tomato plants were: whitefly, broad mites, fruitworm, aphis and leafhopper. The evaluation ...

  7. Evaluating coagulant activity of locally available Syzygium cumini ...

    African Journals Online (AJOL)

    Evaluating coagulant activity of locally available Syzygium cumini , Artocarpus heterophyllus and Moringa oleifera for treatment of community drinking water, ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader).

  8. Evaluating Academic Journals Using Impact Factor and Local Citation Score

    Science.gov (United States)

    Chung, Hye-Kyung

    2007-01-01

    This study presents a method for journal collection evaluation using citation analysis. Cost-per-use (CPU) for each title is used to measure cost-effectiveness with higher CPU scores indicating cost-effective titles. Use data are based on the impact factor and locally collected citation score of each title and is compared to the cost of managing…

  9. Comparative Evaluation of the Effectiveness of sortie local Fabrics ...

    African Journals Online (AJOL)

    Comparative Evaluation of the Effectiveness of sortie local Fabrics for Zooplankton. Harvest. "0v1ts,s 1; Utztowu ... consideration not only in zooplankton field research but also in mass ..... potential of enhancing zooplankton field research/mass ...

  10. Application of the "Personnel Evaluation Standards" to Local District Teacher Evaluation Programs: Analyses of 14 Cases.

    Science.gov (United States)

    Loup, Karen S.; Ellett, Chad D.

    Local school district teacher evaluation plans, processes, and procedures were studied to determine whether they measure up to the criteria outlined by D. Stufflebeam's "Personnel Evaluation Standards" (1988). The applicability and interpretability of the "Standards" across 14 actual cases from local school districts in…

  11. 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.

  12. Retrospective evaluation of adverse drug reactions induced by antihypertensive treatment

    Science.gov (United States)

    Rende, Pierandrea; Paletta, Laura; Gallelli, Giuseppe; Raffaele, Gianluca; Natale, Vincenzo; Brissa, Nazareno; Costa, Cinzia; Gratteri, Santo; Giofrè, Chiara; Gallelli, Luca

    2013-01-01

    The use of cardiovascular drugs is related to the development of adverse drug reactions (ADRs) in about 24% of the patients in the Cardiovascular Care Unit. Here, we evaluated the ADRs in patients treated with antihypertensive drugs. The study was conducted in two phases: In the first phase, we performed a retrospective study on clinical records of Clinical Divisions (i.e., Internal Medicine Operative Unit and Geriatric Operative Unit) from January 1, 2012 to December 31, 2012. Moreover from January 1, 2013 to March 30, 2013 we performed a prospective study on the outpatients attending the Emergency Department (ED) of the Pugliese-Ciaccio Hospital of Catanzaro, by conducting patient interviews after their informed consent was obtained. The association between a drug and ADR was evaluated using the Naranjo scale. We recorded 72 ADRs in the Clinical Divisions and six in the ED, and these were more frequent in women. Using the Naranjo score, we showed a probable association in 92% of these reactions and a possible association in 8%. The most vulnerable age group involved in ADRs was that of the elderly patients. In conclusion, our results indicate that antihypertensive drugs may be able to induce the development of ADRs, particularly in elderly women receiving multiple drug treatment. Therefore, it is important to motivate the healthcare providers to understand their role and responsibility in the detection, management, documentation, and reporting of ADRs, as also all the essential activities for optimizing patient safety. PMID:24347982

  13. Drug-Level Monitoring on Admission for Presurgical Epilepsy Evaluation.

    Science.gov (United States)

    Constantinescu, Irina; Korff, Christian M; Vulliemoz, Serge; Picard, Fabienne; Seeck, Margitta

    2017-01-01

    Evaluation for surgical treatment is offered to patients who do not respond to antiepileptic drugs. Pseudo-pharmacoresistance (PPR) has been described in the context of impaired compliance, incorrect diagnosis of epilepsy or pharmacological interference resulting in too low blood levels. We were interested to determine the frequency and causes of PPR in patients admitted for presurgical evaluation. We reviewed 553 drug levels in 199 patients and analyzed the relative frequency of drugs below reference range (10 and 20% below the range). Patients who had at least one serum level below the 10% cut-off amounted to 33% and 9% of patients had at least one serum level below the 20% cut-off. Only in 2 patients (1%), this was due to poor compliance. Low levels were equally frequent in mono- or polytherapy. Drugs that were most frequently found out of range were phenytoin, valproate, and topiramate. In monotherapy, lamotrigine was often prescribed in too low dosages. Low drug levels are frequently observed in surgical candidates due to pharmacological interference or insufficient dosing. Poor compliance or incorrect diagnosis does not appear to be a significant concern in this patient group. Our data strengthen the need for regular drug monitoring even in advanced chronic epilepsy to avoid unnecessary health costs by too low and ineffective dosages. © 2017 S. Karger AG, Basel.

  14. US-Based Drug Cost Parameter Estimation for Economic Evaluations.

    Science.gov (United States)

    Levy, Joseph F; Meek, Patrick D; Rosenberg, Marjorie A

    2015-07-01

    In the United States, more than 10% of national health expenditures are for prescription drugs. Assessing drug costs in US economic evaluation studies is not consistent, as the true acquisition cost of a drug is not known by decision modelers. Current US practice focuses on identifying one reasonable drug cost and imposing some distributional assumption to assess uncertainty. We propose a set of Rules based on current pharmacy practice that account for the heterogeneity of drug product costs. The set of products derived from our Rules, and their associated costs, form an empirical distribution that can be used for more realistic sensitivity analyses and create transparency in drug cost parameter computation. The Rules specify an algorithmic process to select clinically equivalent drug products that reduce pill burden, use an appropriate package size, and assume uniform weighting of substitutable products. Three diverse examples show derived empirical distributions and are compared with previously reported cost estimates. The shapes of the empirical distributions among the 3 drugs differ dramatically, including multiple modes and different variation. Previously published estimates differed from the means of the empirical distributions. Published ranges for sensitivity analyses did not cover the ranges of the empirical distributions. In one example using lisinopril, the empirical mean cost of substitutable products was $444 (range = $23-$953) as compared with a published estimate of $305 (range = $51-$523). Our Rules create a simple and transparent approach to creating cost estimates of drug products and assessing their variability. The approach is easily modified to include a subset of, or different weighting for, substitutable products. The derived empirical distribution is easily incorporated into 1-way or probabilistic sensitivity analyses. © The Author(s) 2014.

  15. Evaluation of Adverse Drug Reactions to Artemisinin-based ...

    African Journals Online (AJOL)

    ... to evaluate the incidence of adverse reactions to antimalarial drugs among residents of a Nigeria university community with a focus on artemisinin-based combination therapy (ACT). Specifically, the profile of use, and the reporting culture of people with respect to experienced reactions were noted. Method: Questionnaires ...

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

    African Journals Online (AJOL)

    Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v14i3.25. Original Research Article. Evaluation of Information Contained in Drug Advertisement and Promotion Materials in Nigeria. Maxwell Ogochukwu Adibe1*, Nneka Uchenna Igboeli1, Chukwuemeka Michael. Ubaka1, Patrick Obinna Udeogaranya1, ...

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

    African Journals Online (AJOL)

    Stability and drug dissolution evaluation of Qingkailing soft/hard capsules based on multi-component quantification and fingerprint pattern statistical analysis. Ruyu Sun, Huihui Teng, Xiaonan Chen, Shuang Guo, Shan Jia, Mengcheng Zheng, Yang Lu, Jie Bai, Pengyue Li, Shouying Du ...

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

    Science.gov (United States)

    Ziemba, Alexis M; Gilbert, Ryan J

    2017-01-01

    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.

  19. Safety monitoring of local anaesthetic drugs from the perspective of Pharmacovigilance Programme of India

    Directory of Open Access Journals (Sweden)

    Pramod Kumar

    2017-01-01

    Full Text Available Pharmacovigilance Programme of India (PvPI was established to promote patient safety by the Ministry of Health and Family Welfare, Government of India in July 2010. It covers various medical hospitals/institutes and National Health Programmes across the country. India is coordinating with various national and international programmes to be a part of international drug monitoring and to monitor the risk-benefit profile of medicines. At present, India has contributed more than 200,000 adverse drug reactions (ADRs to the database and can draw signals for regulatory decisions. To foster the culture of spontaneous reporting, India has launched paperless and simple modes of reporting ADRs such as Helpline and an Android application. This will help to create a national centre of excellence at par with global drug safety monitoring standards. With the increasing popularity of regional anaesthesia, adverse events may occur due to local anaesthetic drugs, techniques and adjuvants. Uncommon but clinically significant ADRs can be identified in a nationwide pharmacovigilance programme. Anaesthesiologists in India are encouraged to report local anaesthesia-related ADRs to the national pharmacovigilance database.

  20. 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.

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

    Science.gov (United States)

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

    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(-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. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 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

  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 Utility of a Population Approach in Drug-Drug Interaction Assessments: A Simulation Evaluation.

    Science.gov (United States)

    Wang, Diane D; Yu, Yanke; Kassir, Nastya; Zhu, Min; Hanley, William D; Earp, Justin C; Chow, Andrew T; Gupta, Manish; Hu, Chuanpu

    2017-10-01

    This study aims at evaluating the utility of the population pharmacokinetics approach in therapeutic protein drug-drug-interaction (DDI) assessment. Simulations were conducted for 2 representative victim drugs, methotrexate and trastuzumab, using a parallel-group design with and without the interaction drug. The effect of a perpetrator on the exposure of the victim drug is described as the ratio of clearance/apparent clearance of the victim drug given with or without the perpetrator. The power of DDI assessment was calculated as the percentage of runs with 90% confidence interval of the estimated DDI effect within 80% to 125% for the scenarios of no DDI, benchmarked with the noncompartmental approach with intensive sampling. The impact of the number of subjects, the number of sampling points per subject, sampling time error, and model misspecification on the power of DDI determination were evaluated. Results showed that with equal numbers of subjects in each arm, the population pharmacokinetics approach with sparse sampling may need about the same or a higher number of subjects compared to a noncompartmental approach in order to achieve similar power. Increasing the number of subjects, even if only in the study drug alone arm, can increase the power. Sampling or dosing time error had notable impacts on the power for methotrexate but not for trastuzumab. Model misspecification had no notable impacts on the power for trastuzumab. Overall, the population pharmacokinetics approach with sparse sampling built in phase 2/3 studies allows appropriate DDI assessment with adequate study design and analysis and can be considered as an alternative to dedicated DDI studies. © 2017, The American College of Clinical Pharmacology.

  5. Biological evaluation of layered double hydroxides as efficient drug vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Li Yan; Liu Dan; Chang Qing; Liu Dandan; Xia Ying; Liu Shuwen; Peng Nanfang; Yang Xu [Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Huazhong Normal University, Wuhan 430079 (China); Ai Hanhua [College of Physical Science and Technology, Huazhong Normal University, Wuhan 430079 (China); Xi Zhuge, E-mail: yangxu@mail.ccnu.edu.cn [Tianjin Institutes of Health and Environmental Medicine, Tianjin 300050 (China)

    2010-03-12

    Recently there has been a rapid expansion of the development of bioinorganic hybrid systems for safe drug delivery. Layered double hydroxides (LDH), a variety of available inorganic matrix, possess great promise for this purpose. In this study, an oxidative stress biomarker system, including measurement of reactive oxygen species, glutathione content, endogenous nitric oxide, carbonyl content in proteins, DNA strand breaks and DNA-protein crosslinks, was designed to evaluate the biocompatibility of different concentrations of nano-Zn/Al-LDH with a Hela cell line. The drug delivery activity of the LDH-folic-acid complex was also assessed. The resulting data clearly demonstrated that nano-LDH could be applied as a relatively safe drug vehicle with good delivery activity, but with the caveat that the effects of high dosages observed here should not be ignored when attempting to maximize therapeutic activity by increasing LDH concentration.

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

    African Journals Online (AJOL)

    Conclusion: Drug therapy problems among renal patients were high. Inappropriate drug selection and drug interactions were the commonest drug therapy problems. The acceptance of pharmacists' interventions by prescribers was appreciable. Keywords: Drug therapy problems, Renal patients, Therapy, Intervention, ...

  7. 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.

  8. Evaluation of drug provocation test-related anxiety in patients with drug hypersensitivity.

    Science.gov (United States)

    Soyyiğit, Şadan; Aydın, Ömür; Yılmaz, İnsu; Özdemir, Seçil Kepil; Cankorur, Vesile Şentürk; Atbaşoğlu, Cem; Çelik, Gülfem Elif

    2016-09-01

    Drug provocation tests (DPTs) are important in the treatment of patients with drug hypersensitivity (DH), but they carry certain hypersensitivity reaction risks, which lead to procedure-related concerns in patients. To investigate DPT-related anxiety and its effect on long-term use of tested drugs. The study included patients who underwent DPT from July 1, 2009, to July 1, 2012. After recording the patients' history and characteristics, a variety of psychiatric (Hospital Anxiety and Depression Scale, Panic and Agoraphobia Scale, and the Maudsley Obsessive-Compulsive Inventory) and quality-of-life (36-item Short Form Health Survey) tests were performed. DPT-related anxiety was also evaluated using a visual analog scale. The patients were requestioned about whether they had used the tested drug within 1 year. A total of 126 patients were included in the study. According to the Hospital Anxiety and Depression Scale, 23.4% and 30.6% of the patients had depression and anxiety symptoms, respectively. The mean (SD) visual analog scale anxiety scores after a negative DPT result were lower than those before DPTs (2 [2.5] after vs 5.2 [3.4] before; P anxiety related to drug reactions, despite negative DPT results and symptoms indicated for use of the drug. Our findings suggest that DPTs in themselves cause significant anxiety in patients with DH. Importantly, anxiety levels decreased after a negative test result. However, our results also suggested that a negative DPT result is not convincing enough for some patients to use the tested drug when needed in the future. Therefore, supporting strategies appear to be the most effective way to eliminate DH-related anxiety of patients. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Some quantitative evaluations on finite difference local and global results

    Directory of Open Access Journals (Sweden)

    Costamagna Eugenio

    2016-06-01

    Full Text Available Refined Schwarz-Christoffel (SC conformal transformations allow us to perform reliable quantitative evaluation of the accuracy of local computation of electric and magnetic fields with limited effort, which can be useful to complement well known comparisons of global results. In this paper some examples are presented for mesh point potentials obtained by means of finite difference (FD methods, but it is possible that similar considerations will be useful in the case of finite element methods (FEM or meshless computations too.

  10. [Study of local anaesthetics--Part 194. Evaluation of carbopol hydrogels with lidocaine].

    Science.gov (United States)

    Vitková, Zuzana; Herdová, Petra; Cizmárik, Jozef; Zabka, Marián; Brázdovicová, Bronislava; Bockajová, Katarína

    2011-04-01

    The objective of this article is to describe the formulation and evaluation of dermal semisolid drugs--carbopol hydrogels containing the solution of Bukofit, zinc chloride and the local anaesthetic lidocaine. The hydrogels were evaluated after 2, 7, 14 and 28 days after their preparation and stored at the temperature of 5 degrees C +/- 0.2 degrees C. All prepared hydrogels were found to be stable with respect to pH values and rheological parameters. It follows from the found rheological parameters and flow curves that all evaluated hydrogels belong to non-Newtonian thixotropic systems. The extensometric analyses revealed increased deformation values, indicating that the gels can be easily spread out over the mucous membrane which results in the increased ability of the drug to diffuse into it. Based on the results obtained, it can be concluded that the prepared hydrogels have appropriate technological parameters and therefore in the future they may become potential drugs for the treatment of various inflammations in the oral cavity.

  11. An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart.

    Science.gov (United States)

    Pape, A C H; Bakker, Maarten H; Tseng, Cheyenne C S; Bastings, Maartje M C; Koudstaal, Stefan; Agostoni, Pierfrancesco; Chamuleau, Steven A J; Dankers, Patricia Y W

    2015-06-07

    Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the limited access to donor hearts. An example of a treatment to recover the function of the heart consists of the local delivery of drugs and bioactives from a hydrogel. In this paper a method is introduced to formulate and inject a drug-loaded hydrogel non-invasively and side-specific into the pig heart using a long, flexible catheter. The use of 3-D electromechanical mapping and injection via a catheter allows side-specific treatment of the myocardium. To provide a hydrogel compatible with this catheter, a supramolecular hydrogel is used because of the convenient switching from a gel to a solution state using environmental triggers. At basic pH this ureido-pyrimidinone modified poly(ethylene glycol) acts as a Newtonian fluid which can be easily injected, but at physiological pH the solution rapidly switches into a gel. These mild switching conditions allow for the incorporation of bioactive drugs and bioactive species, such as growth factors and exosomes as we present here in both in vitro and in vivo experiments. The in vitro experiments give an on forehand indication of the gel stability and drug release, which allows for tuning of the gel and release properties before the subsequent application in vivo. This combination allows for the optimal tuning of the gel to the used bioactive compounds and species, and the injection system.

  12. 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

    ...; and prescribe sanctions and rewards as appropriate in collaboration with prosecutors, defense attorneys, treatment providers, and others. While some basic requirements are set at the federal level, most decisions about how a drug court operates are left to local jurisdictions.

  13. Intravenous lipids: antidotal therapy for drug overdose and toxic effects of local anesthetics.

    Science.gov (United States)

    Bartlett, Dana

    2014-10-01

    Intravenous lipid emulsion is an accepted therapy for the treatment of severe cardiac toxic effects caused by local anesthetics. Lipid emulsion therapy has also been used successfully to treat cardiac arrest and intractable arrhythmias caused by overdoses of antiepileptic drugs, cardiovascular drugs, and psychotropic medications, but experience with intravenous lipids as antidotal therapy in these clinical situations is limited. However, intravenous lipids are relatively safe, widely available, and easy to administer, and many published case reports document their dramatic effectiveness. Patients who have not responded to standard therapies have been quickly revived by administration of intravenous lipids. Use of lipids most likely will increase, and critical care nurses should be familiar with lipid therapy. ©2014 American Association of Critical-Care Nurses.

  14. Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation.

    Science.gov (United States)

    Zhang, Hao; Tian, Yong; Zhu, Zhenshu; Xu, Huae; Li, Xiaolin; Zheng, Donghui; Sun, Weihao

    2016-05-26

    Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer.

  15. 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.

  16. DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization.

    Science.gov (United States)

    Brecik, Miroslav; Centárová, Ivana; Mukherjee, Raju; Kolly, Gaëlle S; Huszár, Stanislav; Bobovská, Adela; Kilacsková, Emöke; Mokošová, Veronika; Svetlíková, Zuzana; Šarkan, Michal; Neres, João; Korduláková, Jana; Cole, Stewart T; Mikušová, Katarína

    2015-07-17

    The flavo-enzyme DprE1 catalyzes a key epimerization step in the decaprenyl-phosphoryl d-arabinose (DPA) pathway, which is essential for mycobacterial cell wall biogenesis and targeted by several new tuberculosis drug candidates. Here, using differential radiolabeling with DPA precursors and high-resolution fluorescence microscopy, we disclose the unexpected extracytoplasmic localization of DprE1 and periplasmic synthesis of DPA. Collectively, this explains the vulnerability of DprE1 and the remarkable potency of the best inhibitors.

  17. Development and evaluation of an in vitro vaginal model for assessment of drug's biopharmaceutical properties: curcumin

    National Research Council Canada - National Science Library

    Berginc, Katja; Skalko-Basnet, Nataša; Basnet, Purusotam; Kristl, Albin

    2012-01-01

    Vaginal administration is a promising alternative to the per-oral route in achieving systemic or local therapeutic effects, when intestinal drug absorption is hindered by problematic biopharmaceutical drug properties...

  18. 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

  19. 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

  20. From Words to Action: Comparing the Disparities Between National Drug Policy and Local Implementation in Tijuana, Mexico and Vancouver, Canada

    OpenAIRE

    Smith, Danielle; Werb, D.; Strathdee, S. A.

    2016-01-01

    In 2009, Mexico passed a national drug policy reform decriminalizing the possession of small amounts of certain drugs for personal use with the aim of diverting drug-dependent individuals from prison and towards addiction treatment. However, the public health approach codified by the reform has not yet led to a meaningful change in local police practices nor contributed to the meaningful scale-up of harm reduction and addiction treatment services in many Mexican cities. Specifically, in Tijua...

  1. Drug coated microneedles for minimally-invasive treatment of oral carcinomas: development and in vitro evaluation.

    Science.gov (United States)

    Ma, Yunzhe; Boese, Seth E; Luo, Zhen; Nitin, Nitin; Gill, Harvinder S

    2015-04-01

    Treatment of recurring oral cancers is challenging as common surgical approaches are not feasible for these patients. In addition, these patients do not respond well to systemic chemotherapy. Localized intratumoral injection of anti-cancer drugs is considered to be an attractive alternative treatment approach for these patients. However, conventional hypodermic injections result in poor distribution of the drug in the tumor and leakage of the drug from the injection site to systemic circulation, in addition to causing pain to the patient. The objective of this study was to develop coated microneedles as a novel device for direct and minimally invasive intratumoral delivery of anti-cancer drugs. Poly(lactic-co-glycolic) acid (PLGA) nanoparticles encapsulating doxorubicin (DOX) were prepared and coated on inplane (1D) microneedles. Microscopic evaluation of 3D tissue phantoms and porcine cadaver buccal tissues that were treated with 1D microneedle arrays coated with DOX-PLGA nanoparticles demonstrated that DOX could diffuse both laterally and vertically in to the tissues and produced cellular cytotoxicity. Out of plane (2D) microneedle arrays measuring 1 cm x 1 cm with 57 microneedles coated with free DOX could produce uniform distribution of DOX in a porcine cadaver buccal tissue up to a depth greater than 3 mm. Hypodermic injection of different volumes in to a porcine buccal tissue confirmed significant leakage of the injected volume (about 25% of the injected 80 μl). In summary, this study demonstrates that drug coated microneedles is an attractive microscale device that can uniformly and effectively deliver drugs to localized oral cancers. This microscale device has potential to impact the treatment of oral cancer patients.

  2. Therapeutic effects of local drug delivery systems - PerioChip® in the treatment of periodontal disease

    Directory of Open Access Journals (Sweden)

    Liljana Bogdanovska

    2014-03-01

    Full Text Available The primary goal of periodontal treatment is to stop periodontal disease progression and reduce future risks in disease recurrence. In order to overcome the limitations of the conventional treatment, controlled drug delivery systems for application in periodontal pockets have been developed. Their use offers several advantages: the therapeutic agent is targeted directly to the disease site and concentrations are 10-100 folds higher than the concentrations achieved by systemic administration, with low incidence of side effects. The PerioChip® is as local controlled-release biodegradable delivery system containing chlorhexidine digluconate. Several multicenter clinical trials have shown that the application of the PerioChip® in periodontal pockets as adjunct to the conventional periodontal treatment significantly improved the clinical parameters. In this article, the results from controlled clinical studies aimed to evaluate the clinical and microbiological efficacy of the PerioChip®, are discussed.

  3. 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.

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

    National Research Council Canada - National Science Library

    Munksgaard, Rasmus; Demant, Jakob; Branwen, Gwern

    2016-01-01

    .... 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...

  5. Hypersensitivity to local anaesthetics--update and proposal of evaluation algorithm

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Menné, Torkil; Elberling, Jesper

    2008-01-01

    of patients suspected with immediate- and delayed-type immune reactions. Literature was examined using PubMed-Medline, EMBASE, Biosis and Science Citation Index. Based on the literature, the proposed algorithm may safely and rapidly distinguish between immediate-type and delayed-type allergic immune reactions.......Local anaesthetics (LA) are widely used drugs. Adverse reactions are rare but may be caused by delayed-type hypersensitivity reactions and probably also immediate-type reactions. As it is not always easy to clinically differ between these subtypes, allergy skin testing should be considered....... Although numerous test protocols have been published, how patients with hypersensitivity reactions to LA are ideally evaluated remains a topic of discussion. This review attempts to generate a comprehensive update on allergic reactions to LA and to present an algorithm that can be used for the evaluation...

  6. Hypersensitivity to local anaesthetics--update and proposal of evaluation algorithm

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Menné, Torkil; Elberling, Jesper

    2008-01-01

    Local anaesthetics (LA) are widely used drugs. Adverse reactions are rare but may be caused by delayed-type hypersensitivity reactions and probably also immediate-type reactions. As it is not always easy to clinically differ between these subtypes, allergy skin testing should be considered....... Although numerous test protocols have been published, how patients with hypersensitivity reactions to LA are ideally evaluated remains a topic of discussion. This review attempts to generate a comprehensive update on allergic reactions to LA and to present an algorithm that can be used for the evaluation...... of patients suspected with immediate- and delayed-type immune reactions. Literature was examined using PubMed-Medline, EMBASE, Biosis and Science Citation Index. Based on the literature, the proposed algorithm may safely and rapidly distinguish between immediate-type and delayed-type allergic immune reactions....

  7. Effect of local drug delivery in chronic periodontitis patients: A meta-analysis.

    Science.gov (United States)

    Kalsi, Rupali; Vandana, K L; Prakash, Shobha

    2011-10-01

    Periodontal diseases are multi-factorial in etiology, and bacteria are one among these etiologic agents. Thus, an essential component of therapy is to eliminate or control these pathogens. This has been traditionally accomplished through mechanical means (scaling and root planing (SRP)), which is time-consuming, difficult, and, sometimes, ineffective. From about the past 30 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal. This systematic review is an effort to determine the efficacy of the currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis. Four studies were included, which were all randomized controlled trials, incorporating a total patient population of 80, with 97 control sites and 111 test sites. A meta-analysis completed on these four studies including SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive probing depth (PD) reduction for 10% Doxycycline hycylate (ATRIDOX), minocycline hydrochloride (ARESTIN), tetracycline hydrochloride (PERIODONTAL PLUS AB), and chlorhexidine gluconate (PERIOCHIP). Essentially, all studies reported substantial reductions in gingival inflammation, plaque scores, and bleeding indices, which were similar in both the control and the experimental groups. Use of antimicrobial sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events. Local drug delivery combined with SRP appears to provide additional benefits in PD reduction compared with SRP alone.

  8. Comparative Evaluation of the Effectiveness of some local Fabrics ...

    African Journals Online (AJOL)

    Ovic et (11., 1993, and. Ovie and Egborge, 2002), this study has shown that locally available local fabrics are good and inexpensive fabrics for zooplankton harvest. In particular, the local fabric, poplin can be employed even in field research, ...

  9. Development of potential orphan drug therapy of intravesical liposomal tacrolimus for hemorrhagic cystitis due to increased local drug exposure.

    Science.gov (United States)

    Nirmal, Jayabalan; Tyagi, Pradeep; Chancellor, Michael B; Kaufman, Jonathan; Anthony, Michele; Chancellor, David D; Chen, Yen-Ta; Chuang, Yao-Chi

    2013-04-01

    The potent immunosuppressive effect of systemic tacrolimus is limited by the high incidence of severe adverse effects, including nephrotoxicity and hypertension. Intravesical application of tacrolimus is hindered by its poor aqueous solubility, justifying the search for novel delivery platforms such as liposomes. We evaluated the pharmacokinetics of tacrolimus encapsulated in liposomes (lipo-tacrolimus), which is being developed as a potential orphan drug indication for hemorrhagic cystitis. A single dose of lipo-tacrolimus was instilled in the bladder with the rat under anesthesia. Also, tacrolimus was instilled intravesically or injected intraperitoneally in other rat groups. The tacrolimus dose was constant in all formulations at 200 μg/ml. At different times blood, urine and bladder samples were collected and stored at -80C until analysis. Tacrolimus levels in samples were analyzed using microparticle enzyme immunoassay II. The AUC of lipo-tacrolimus in serum at 0 to 24 hours was significantly lower than that of tacrolimus instillation or injection. Noncompartmental pharmacokinetic data analysis revealed maximum concentration of lipo-tacrolimus and tacrolimus in serum and urine at 1 and at 2 hours, respectively. Urine AUC(0-24) after intravesical administration was significantly higher than in the intraperitoneal group (p hemorrhagic cystitis. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. SBA-15 ordered mesoporous silica inside a bioactive glass-ceramic scaffold for local drug delivery.

    Science.gov (United States)

    Cauda, V; Fiorilli, S; Onida, B; Vernè, E; Vitale Brovarone, C; Viterbo, D; Croce, G; Milanesio, M; Garrone, E

    2008-10-01

    The paper reports the synthesis of an ordered silica mesostructure of the SBA-15 type inside a macroporous bioactive glass-ceramic scaffold of the type SiO(2)-CaO-K(2)O, to combine the bioactivity of the latter with the release properties of the former, in view of local drug delivery from implants designed for tissue engineering. The standard procedure for SBA-15 synthesis has been modified to minimize the damage to the scaffold caused by the acidic synthesis medium. The composite system has been characterized by means of Scanning Electron Microscopy (coupled with EDS analysis), Small Angle X-Ray Diffraction, Thermogravimetry analysis and Infrared Spectroscopy: the formation of a well ordered hexagonal mesostructure was confirmed. Ibuprofen has been chosen as model drug. The uploading properties have been investigated of the scaffold-mesoporous silica composite as compared with the scaffold as such, and a five-fold increase in the adsorbing properties toward ibuprofen was found, due to the presence of the ordered mesoporous silica. The ibuprofen release to a SBF solution in vitro is complete in 1 day. Retention of bioactivity from the glass-ceramic scaffold after the silica mesostructure incorporation has been observed.

  11. 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.

  12. 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.

  13. 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.

  14. In vitro bioequivalence approach for a locally acting gastrointestinal drug: lanthanum carbonate.

    Science.gov (United States)

    Yang, Yongsheng; Shah, Rakhi B; Yu, Lawrence X; Khan, Mansoor A

    2013-02-04

    A conventional human pharmacokinetic (PK) in vivo study is often considered as the "gold standard" to determine bioequivalence (BE) of drug products. However, this BE approach is not always applicable to the products not intended to be delivered into the systemic circulation. For locally acting gastrointestinal (GI) products, well designed in vitro approaches might be more practical in that they are able not only to qualitatively predict the presence of the active substance at the site of action but also to specifically assess the performance of the active substance. For example, lanthanum carbonate chewable tablet, a locally acting GI phosphate binder when orally administrated, can release free lanthanum ions in the acid environment of the upper GI tract. The lanthanum ions directly reach the site of action to bind with dietary phosphate released from food to form highly insoluble lanthanum-phosphate complexes. This prevents the absorption of phosphate consequently reducing the serum phosphate. Thus, using a conventional PK approach to demonstrate BE is meaningless since plasma levels are not relevant for local efficacy in the GI tract. Additionally the bioavailability of lanthanum carbonate is less than 0.002%, and therefore, the PK approach is not feasible. Therefore, an alternative assessment method is required. This paper presents an in vitro approach that can be used in lieu of PK or clinical studies to determine the BE of lanthanum carbonate chewable tablets. It is hoped that this information can be used to finalize an in vitro guidance for BE studies of lanthanum carbonate chewable tablets as well as to assist with "in vivo" biowaiver decision making. The scientific information might be useful to the pharmaceutical industry for the purpose of planning and designing future BE studies.

  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

    2018-01-04

    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. 75 FR 34452 - Center for Drug Evaluation and Research Data Standards Plan; Availability for Comment

    Science.gov (United States)

    2010-06-17

    ... HUMAN SERVICES Food and Drug Administration Center for Drug Evaluation and Research Data Standards Plan... development of a comprehensive data standards program in the Center for Drug Evaluation and Research (CDER... Administration (FDA) is announcing the availability for public comment of the draft document entitled ``CDER Data...

  18. Evaluation of a procedure to assess the adverse effects of illicit drugs.

    NARCIS (Netherlands)

    Amsterdam, J G C van; Best, W; Opperhuizen, A; Wolff, F A de

    2004-01-01

    The assessment procedure of new synthetic illicit drugs that are not documented in the UN treaty on psychotropic drugs was evaluated using a modified Electre model. Drugs were evaluated by an expert panel via the open Delphi approach, where the written score was discussed on 16 items, covering

  19. Evaluation of Public Service Advertising Messages with Local and Non-Local Source Attribution: A Controlled Laboratory Experiment.

    Science.gov (United States)

    Lynn, Jerry R.; Gagnard, Alice

    A study was conducted to examine message evaluations of selected public service advertisements (PSAs) by a young adult population and to test whether local and nonlocal source attribution would influence those evaluations. In addition, the study investigated the extent to which audience characteristics such as fatalism (the degree to which a…

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

    African Journals Online (AJOL)

    Objective: The aim of this work was to contribute to the food safety of Ivorian consumers by investigating the nutritive value and the microbial quality of local cereal flours offered for retail sale on different markets located on selected areas of the District of Abidjan. Methodology and results: Local cereal flours samples were ...

  1. Evaluating drug efficacy and toxicology in three dimensions: using synthetic extracellular matrices in drug discovery.

    Science.gov (United States)

    Prestwich, Glenn D

    2008-01-01

    The acceptance of the new paradigm of 3-D cell culture is currently constrained by the lack of a biocompatible material in the marketplace that offers ease of use, experimental flexibility, and a seamless transition from in vitro to in vivo applications. I describe the development of a covalently cross-linked mimic of the extracellular matrix (sECM), now commercially available, for 3-D culture of cells in vitro and for translational use in vivo. These bio-inspired, biomimetic materials can be used "as is" in drug discovery, toxicology, cell banking, and, ultimately, medicine. For cell therapy and the development of clinical combination products, the sECM biomaterials must be highly reproducible, manufacturable, approvable, and affordable. To obtain integrated, functional, multicellular systems that recapitulate tissues and organs, the needs of the true end users, physicians and patients, must dictate the key design criteria. In chemical terms, the sECM consists of chemically-modified hyaluronan (HA), other glycosaminoglycans (GAGs), and ECM polypeptides containing thiol residues that are cross-linked using biocompatible polyvalent electrophiles. For example, co-cross-linking the semisynthetic thiol-modified HA-like GAG with thiol-modified gelatin produces Extracel as a hydrogel. This hydrogel may be formed in situ in the presence of cells or tissues to provide an injectable cell-delivery vehicle. Alternately, an Extracel hyrogel can be lyophilized to create a macroporous scaffold, which can then be employed for 3-D cell culture. In this Account, we describe four applications of sECMs that are relevant to the evaluation of drug efficacy and drug toxicity. First, the uses of sECMs to promote both in vitro and in vivo growth of healthy cellularized 3-D tissues are summarized. Primary or cell-line-derived cells, including fibroblasts, chondrocytes, hepatocytes, adult and embryonic stem cells, and endothelial and epithelial cells have been used. Second, primary

  2. Clinical evaluation of 30 patients with localized nasal rosacea.

    Science.gov (United States)

    Lee, Woo Jin; Lee, Ye Jin; Won, Chong Hyun; Chang, Sung Eun; Choi, Jee Ho; Lee, Mi Woo

    2016-02-01

    The clinical features of localized nasal rosacea have not been described in detail. This study was designed to analyze the subtypes and severity of localized nasal rosacea. Our present study included 30 patients with localized nasal rosacea. The erythematotelangiectatic subtype (13/30, 43.3%) was the most common type, followed by the phymatous subtype (9/30, 30%). The duration of rosacea was shorter and the severity of localized nasal rosacea was lower in the erythematotelangiectatic subtype cases compared with the patients with mixed or phymatous subtypes. Almost all of the papulopustular eruptions or phymatous lesions were associated with erythematotelangiectatic lesions. These findings suggest that the erythematotelangiectatic subtype may be considered the initial phase of localized nasal rosacea. © 2015 Japanese Dermatological Association.

  3. Evaluation of potential pharmacokinetic drug-drug interaction between armodafinil and risperidone in healthy adults.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Yang, Ronghua; Hellriegel, Edward T; Robertson, Philmore

    2015-11-01

    Patients with bipolar I disorder and schizophrenia have an increased risk of obstructive sleep apnea. The effects of armodafinil, a weak cytochrome P450 (CYP) 3A4 inducer, on pharmacokinetics and safety of risperidone, an atypical antipsychotic used to treat major psychiatric illness, were investigated. Healthy subjects received 2 mg risperidone alone and after armodafinil pretreatment (titrated to 250 mg/day). Pharmacokinetic parameters were derived from plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone (formed via CYP2D6 and CYP3A4), collected before and over 4 days after risperidone administration, and from steady-state plasma concentrations of armodafinil and its circulating metabolites, R-modafinil acid and modafinil sulfone. Safety and tolerability were assessed. Thirty-six subjects receiving study drug were evaluable for safety; 34 were evaluable for pharmacokinetics. Risperidone maximum plasma concentration (C max) decreased from mean 16.5 ng/mL when given alone to 9.2 ng/mL after armodafinil pretreatment (geometric mean ratio [90 % CI] 0.55 [0.50-0.61]); area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) decreased from 92.3 to 44.5 ng·h/mL (geometric mean ratio [90 % CI] 0.51 [0.46-0.55]). C max and AUC0-∞ for 9-hydroxyrisperidone were also reduced (geometric mean ratios [90 % CI] 0.81 [0.77-0.85] and 0.73 [0.69-0.77], respectively). Adverse events were consistent with known safety profiles. Consistent with CYP3A4 induction, risperidone and 9-hydroxyrisperidone systemic exposure was reduced in the presence of armodafinil. Concomitant armodafinil and risperidone use may necessitate risperidone dosage adjustment, particularly when starting or stopping coadministration of the two drugs. However, any such decision should be based on patient disease state and clinical status.

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2010-03-01

    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.

  7. An ex Vivo Model for Evaluating Blood-Brain Barrier Permeability, Efflux, and Drug Metabolism

    DEFF Research Database (Denmark)

    Hellman, Karin; Aadal Nielsen, Peter; Ek, Fredrik

    2016-01-01

    , risperidone, citalopram, fluoxetine, and haloperidol were studied, and one preselected metabolite for each drug was analyzed, identified, and quantified. Metabolite identification studies of clozapine and midazolam showed that the locust brain was highly metabolically active, and 18 and 14 metabolites......, respectively, were identified. The unbound drug fraction of clozapine, NDMC, carbamazepine, and risperidone was analyzed. In addition, coadministration of drugs with verapamil or fluvoxamine was performed to evaluate drug-drug interactions in all setups. All findings correlated well with the data...

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

    OpenAIRE

    Stumpf, W.E.

    1998-01-01

    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 ...

  9. Comparative evaluation of drug release from aged prolonged polyethylene oxide tablet matrices: effect of excipient and drug type.

    Science.gov (United States)

    Shojaee, Saeed; Kaialy, Waseem; Cumming, Kenneth Iain; Nokhodchi, Ali

    2016-03-01

    Polyethylene oxide (PEO) undergoes structural adjustments caused by elevated temperatures, which results in loss of its stability within direct compression tablets. The aim of this study was to evaluate the influence of filler solubility on the drug delivery process of matrix tablets containing drugs with different water-solubility properties and stored at elevated temperature. The results demonstrated that in the case of propranolol HCl (highly water-soluble) tablet matrices, soluble lactose promoted drug release, whereas, a stable release of drug was observed with insoluble DCP. A drug release pattern similar to the propranolol HCl formulation containing DCP was obtained for hydrophilic matrix tablets containing either lactose or DCP for the less water-soluble drug, zonisamide. In the case of the partially water-soluble drug, theophylline, formulated with lower molecular weight PEO 750, drug release increased considerably in the presence of both fillers with increasing storage time, however a stable release rate (similar to fresh samples) was observed in the case of higher molecular weight PEO 303 tablet matrices containing theophylline with either lactose or DCP. The hydration properties (e.g. solubility) of the diluents had a considerable effect on drug release behavior from various model matrices; this effect was dependent on both molecular weight of PEO and solubility of drug.

  10. 78 FR 8446 - Center for Drug Evaluation and Research; Prescription Drug Labeling Improvement and Enhancement...

    Science.gov (United States)

    2013-02-06

    ... prescription drug products and reducing the likelihood of medication errors. FDA implemented standardized... voluntarily converts to PLR format. \\4\\ Data obtained from http://labels.fda.gov . Generic drugs approved... show that only 10 percent of generic drug labeling has been converted to the PLR format.\\5\\ Since...

  11. Synthesis, drug release, and biological evaluation of new anticancer drug-bioconjugates containing somatostatin backbone cyclic analog as a targeting moiety.

    Science.gov (United States)

    Redko, Boris; Ragozin, Elena; Andreii, Bazylevich; Helena, Tuchinsky; Amnon, Albeck; Talia, Shekhter Zahavi; Mor, Oron-Herman; Genady, Kostenich; Gary, Gellerman

    2015-11-01

    Peptide conjugates containing somatostatin (SST) cyclic analogs as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing SST receptors (SSTRs), and hence increasing their local efficacy while limiting the peripheral toxicity. Here, we report on the synthesis and biochemical characterization of new SSTR-specific anticancer peptide conjugates, with different anticancer payloads acting through different oncogenic mechanisms to evaluate their biological activities and to provide a comparative study of their drug release profiles. The SSTR2-specific backbone cyclic peptide 3207-86 was chosen for the synthesis of a variety of novel anticancer drug conjugates with a broad drug release capabilities. The N-terminus of 3207-86 was equipped with GABA to generate free amino group available for the conjugation of chlorambucil, Camptothecin (CPT), Combretastatin 4A, ABT-751, and Amonafide through the formation of various biodegradable bonds. The chemo- and biostability/drug release of all the synthetic compounds was investigated at various pHs and in the presence of mouse liver homogenate, respectively. Their selective cytotoxic effect was evaluated on several human cancer cell lines that overexpress SSTR2. Compared with the free drugs, our peptide-drug conjugates exhibited considerable cytotoxic effect on cancer cell lines versus low SSTR2-expressed human embryonic kidney cells. Functional versatility of the conjugates was reflected in the variability of their drug release profiles, whereas the conserved sequence of a selective binding to the SSTR2 likely preserved their binding to the receptor and consequently their favorable toxicity toward targeted cancer cells. © 2015 Wiley Periodicals, Inc.

  12. 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.

  13. Solid state characterization of hydroxyprocaine hydrochloride. Crystal polymorphism of local anaesthetic drugs, part VIII

    Science.gov (United States)

    Schmidt, A. C.; Schwarz, I.

    2005-06-01

    Two polymorphic and a pseudopolymorphic crystal form of the local anaesthetic drug hydroxyprocaine hydrochloride (4-Butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, HPCHC) are characterized by thermal analysis (hot stage microscopy, differential scanning calorimetry, thermogravimetry), spectroscopy (FTIR-, FT-Raman-, SSNMR-spectroscopy), powder X-ray diffractometry and water vapor sorption analysis. The formation and thermodynamic stability of the different solid phases is described and presented in a flow chart and in an energy/temperature diagram, respectively. Mod. II° is the thermodynamically stable form at room temperature and present in commercial products mostly contaminated with a hydrated form which is isostructural with the unstable mod. I. The stable mod. II° crystallizes from most organic solvents in combination with seeds of the metastable mod. I and from the melt below 130 °C. Pure mod. I crystallizes from the melt at temperatures above 130 °C and additionally appears on dehydration of the hydrate. According to the heat of fusion rule, mod. I is the thermodynamically less stable form below the transition temperature (enantiotropism). The sorption isotherms show a distinct lower hygroscopicity for the stable mod. II°, whereas the unstable mod. I converts to the hydrate under moisture conditions above 0% RH at room temperature.

  14. 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.

  15. 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.

  16. Metronidazole and Pentoxifylline films for the local treatment of chronic periodontal pockets: preparation, in vitro evaluation and clinical assessment.

    Science.gov (United States)

    Labib, Gihan S; Aldawsari, Hibah M; Badr-Eldin, Shaimaa M

    2014-06-01

    Periodontitis is one of the most important chronic inflammatory dental diseases arising from the destructive actions caused by a variety of pathogenic organisms presented in the oral cavity. The aim of this study is the preparation and in vitro evaluation of films for the local treatment of periodontal pockets. The prepared films contained either metronidazole (Mtr), for its antimicrobial effect in periodontal diseases, using a mixture of polymers namely hydroxypropyl methyl cellulose, Carbopol 934 or locally applied Pentoxifylline (PTX), for its anti-inflammatory activity, using chitosan. All films were prepared using solvent casting technique and were evaluated for their physical characteristics, drug content uniformity, surface pH, swelling behavior, mechanical properties and in vitro release. Further characterization was done on the selected formulations using differential scanning calorimetry and scanning electron microscopy for surface structure. Clinical evaluation tests were also performed. Appropriate physical characteristics and mechanical properties for most formulations and their suitability for periodontal application were observed. In vitro drug release from most films showed a burst release rate for both Mtr and PTX during the first 2 h after which the release rate was markedly decreased. Clinical trials on patients revealed the advantageous use of Mtr and PTX as an adjunct treatment with traditionally used dental techniques. The effectiveness of the co-therapy of either drug could add benefit in the eradication of chronic periodontal hazards.

  17. Poly(methyl methacrylate) particles for local drug delivery using shock wave lithotripsy: In vitro proof of concept experiment.

    Science.gov (United States)

    Shaked, Eliav; Shani, Yoav; Zilberman, Meital; Scheinowitz, Mickey

    2015-08-01

    To leverage current local drug delivery systems methodology, there is vast use of polymeric particles serving as drug carriers to assure minimal invasive therapy with little systemic distribution of the released drug. There is an increasing interest in poly(methyl methacrylate) (PMMA) serving as carriers in drug delivery. The study aims to develop PMMA carriers for localized drug delivery and release system, combining innovative biomaterial technology and shock wave lithotripsy (SWL), and to study the effect of SWL on various concentrations of PMMA particles. We prepared PMMA particles that contain horseradish peroxidase (HRP) using a double emulsion technique, and investigated the mechanism of in vitro drug release from the carriers following exposure to SWL. We investigated the correlation between production method modifications, concentrations of the carriers subjected to SWL, and shock wave patterns. We successfully produced PMMA particles as drug carriers and stimulated the release of their contents by SWL; their polymeric shell can be shattered externally by SWL treatment, leading to release of the encapsulated drug. HRP enzyme activity was maintained following the encapsulation process and exposure to high dose of SWL pulses. Increased shock wave number results in increased shattering and greater fragmentation of PMMA particles. The results demonstrate a dose-response release of HRP; quantitation of the encapsulated HRP from the carriers rises with the number of SWL. Moreover, increased concentration of particles subjected to the same dose of SWL results in a significant increase of the total HRP release. Our research offers novel technique and insights into new, site-specific drug delivery and release systems. © 2014 Wiley Periodicals, Inc.

  18. [Evaluation of efficacy and safety of drugs absorbed through skin using their physicochemical parameters].

    Science.gov (United States)

    Oshizaka, Takeshi; Todo, Hiroaki; Sugibayashi, Kenji

    2012-01-01

    Skin has been paid attention as a site of application of prescription drugs, over-the-counter drugs (non-prescription drugs) and cosmetics. Skin permeation and skin concentration of the compounds should be considered after topical administration, as well as their blood concentration to evaluate efficacy and safety. Since the evaluation of the amount of drugs permeated through skin is important for topically applied drugs, studies on the skin permeation has been greatly advanced. In addition, many reports proved that skin permeabilities of drugs could be predicted from physicochemical parameters of drugs. On the other hand, few reports have been found on the prediction of skin concentration of drugs. Furthermore, many experimented problems are left to determine the skin concentration of drugs: severe consume of human or animal skins, difficult removal of applied drugs from the skin surface, low drug extraction ratio from skin and low sensitivity to determine skin concentration of drugs, and requirement of long time measurement. Thus, fast and accurate measurement of skin concentration of applied drugs are urgently required. This report describes the relationship between skin permeation and skin concentration, and the prediction of skin concentration of drugs using skin permeation parameters of drugs.

  19. Evaluation of four local plant species for insecticidal activity against ...

    African Journals Online (AJOL)

    Les propriétés insecticides de quatre plantes médicinales locales: Ricinus communis Linn. (haricot de ricin), Jatropha curcas Linn. (noix de purge/corail), Anacardium occidentale Linn. (noix de cajou), et Erythrophleum sauveolens (le mançone) étaient étudiées sous les conditions de laboratoire contre deux ravageurs de ...

  20. Evaluation of Local Vegetable Oils as Quenchants for Hardening ...

    African Journals Online (AJOL)

    However, the wear resistance of the quenched grey cast iron developed in this group of local vegetable oils was superior to that of SAE40 engine oil. The potentials of these oils as quenching media for grey cast iron hardening process ranked in descending order as soya bean, shea butter, groundnut, and palm kernel, with ...

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

    African Journals Online (AJOL)

    synthesis in the hypothalamus. CONCLUSION. In conclusion, the present study showed that an aqueous extract of plant C. officinalis had local anesthetic and anti-pyretic activity in guinea pigs, frogs, and rats. Because this is a preliminary report, further studies are needed to analyze the possible mechanisms of action.

  2. Economic evaluation of a locally fabricated extraction machine for a ...

    African Journals Online (AJOL)

    Work has been on for some time now at CRIN to harness this wastage into commercially viable human foods or food ingredients. Much progress has been made to-date on the production of juice from the apple. This study assesses the cottage utilisation of the apple using a locally fabricated extraction machine.

  3. Performance Evaluation of Wastewater Treated Plant for Ninava Drug Factory

    Directory of Open Access Journals (Sweden)

    Amar Hamad

    2013-05-01

    Full Text Available In this study the characteristics of raw and treated wastewater from Ninava drug factory were evaluated. The results revealed that the strength of raw wastewater can be classified as medium concentrated wastewater with respect to its BOD5 since the average value is 231.7 mg/l. In addition a strong correlations were found between many characteristics of raw waste. The characteristics of produced effluent from waste water treatment plant of the factory were within the Iraqi specification for the disposed wastewater constraints in 1997, where the average is 7.8 for pH, 40mg/l for SS, 2.8 mg/l for PO4-3, 45 mg/l for BOD5 and 104.3 mg/l for COD. The heavy metals concentrations for both raw and treated wastewater is to be less than those of the related literatures for Tigris river, municipal wastewater and water supply in Mosul city, the average heavy metal concentrations of raw and treated wastewater were 0.5 mg/l for Iron, 0.2 mg/l for zinc and 0.005 mg/l for copper, and there is no significant difference between raw and treated heavy metal concentrations.

  4. Efficacy evaluation of syringe pump developed for continuous drug infusion.

    Science.gov (United States)

    Jung, Bongsu; Seo, Kwang-Suk; Kwon, Suk Jin; Lee, Kiyoung; Hong, Suyong; Seo, Hyounsoon; Kim, Gi-Young; Park, Geun-Mook; Jeong, Juhee; Seo, Soowon

    2016-12-01

    In dental intravenous sedation, continuous intravenous infusion of a low-dose drug requires an infusion pump such as a syringe pump. To develop a new syringe pump for clinical use, the functions of the pump must meet certain international standards. Various safety and efficacy tests must be performed on the syringe pump, as stipulated by these standards, and an approval must be received from the approving agency based on such test results. The authors of the present study developed a novel syringe pump and performed efficacy evaluation by testing its infusion speed at 1 and 25 ml/h, and infusion performance testing at 2 and 24 h. Moreover, performance evaluation was conducted by comparing the novel pump to an existing pump with the infusion speed varied from 1 to 5 ml/h. In the efficacy testing on the newly developed syringe pump, infusion with the infusion speed initially set to 1 ml/h resulted in infusion speeds of 1.00 and 0.99 ml/h in the 2- and 24-h assessment, respectively. Changing the infusion speed setting to 25 ml/h resulted in an infusion speed of 25.09 and 23.92 ml/h in the 2- and 24-h assessment, respectively. These results show no significant differences when compared with other commercially available pumps. The efficacy testing of the newly developed syringe pump showed the accuracy to be within tolerance. Based on these findings, we believe that the newly developed syringe pump is suitable for clinical use.

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

    Science.gov (United States)

    2011-11-23

    ...: The Food and Drug Administration (FDA) is announcing the availability of draft guidance for industry... Doc No: 2011-30149] 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...

  6. Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits.

    Science.gov (United States)

    Gong, Yuping; Wang, Zhigang; Dong, Guifang; Sun, Yang; Wang, Xi; Rong, Yue; Li, Maoping; Wang, Dong; Ran, Haitao

    2016-09-01

    To explore the antitumor effects of low-intensity focused ultrasound (LIFU) mediated localized drug delivery of adriamycin-microbubble-PLGA nanoparticle complexes on rabbits VX2 liver tumor. ADM-NMCs were prepared by covalent linking of ADM-PLGA nanoparticles (ADM-NPs) to the shell of the microbubbles. A fixed water bag filled with microbubbles was subjected to LIFU and non-focused ultrasound respectively, and the ultrasound images of which were recorded before and after ultrasonication. A total of 54 VX2 liver tumor-burdened rabbits were divided into six groups randomly, including control, ADM-NPs combined with LIFU, microbubbles combined with LIFU, ADM-NPs and microbubbles combined with LIFU, ADM-NMCs combined with LIFU and ADM-NMCs combined with Non-FUS. The tumor volume and volume inhibition rate (VIR) of tumor progression were calculated and compared. Apoptotic cells were labeled by terminal deoxyuridine nick end. Proliferating cell nuclear antigen was detected by immunohistochemistry. The median survival time of the animals were recorded and compared. ADM-NMCs were successfully prepared with an average diameter of 1721 nm. The highest VIR and apoptotic index (AI) were found in the group of ADM-NMCs combined with LIFU while the lowest proliferating index (PI) was simultaneously observed in this group. The median survival time of the rabbits in the ADM-NMCs combined with LIFU group was the longest (71days) among all groups. ADM-NMCs combined with LIFU could inhibit the rabbits VX2 liver tumor progress by delaying the tumor proliferation and accelerating apoptosis, which presents a novel process for liver tumor targeting chemotherapy.

  7. 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.

  8. 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.

  9. [Evaluation of a programme to monitor drug therapy in type-2 diabetics].

    Science.gov (United States)

    Fornos Pérez, J A; Guerra García, M M; Andrés Rodríguez, N F; Egea Ibernón, B

    2004-06-15

    To evaluate the results of pharmaceutical intervention in a programme to monitor the drug therapy of type-2 diabetics; and to assess the improvement of the indicators, glycosylated haemoglobin, basal glycaemia, lipid profile, albumin/creatinine, blood pressure, BMI, medication-related problems and adherence. Randomised clinical trial. 14 local pharmacies in the province of Pontevedra (Galicia), Spain. 126 type-2 diabetics, over 18 years old and who joined voluntarily a monitoring programme, distributed 50-50 into intervention and control groups. The main variable was HbA1c. Other variables were: clinical indicators of metabolic control (mean basal glycaemia, lipid profile), blood pressure, BMI, medication-related problems, understanding of the illness and its complications, adherence to medical treatment and to changes in life-style, and incidence of complications. Introduction and randomisation of patients. Recording of the initial status of the research variables, study and assessment stage, pharmaceutical interventions to detect and resolve any passing medication-related problems and educational activities. Referral to family doctor if his/her intervention required. Follow-up lasted 12 months with monthly scheduled visits and on-demand visits, after which the variables were assessed once more. The stages of study, evaluation, intervention and education did not occur in the control group. The study will enable the role of the chemist in achieving the objectives of controlling type-2 diabetes patients to be achieved through educational intervention and assistance in drug therapy monitoring.

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

    African Journals Online (AJOL)

    (55.0 %), drug interaction (51.3 %), pharmacokinetics (36.3 %) and revision date of the information. (21.0 %). Conclusion: This study reveals that advertising materials used in promoting drugs in Nigeria have incomplete information and the physical characteristics of the materials are not adequate. It seems that.

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

    African Journals Online (AJOL)

    Other contents of the materials were mechanism of action (70.3 %), overdoses information (55.0 %), drug interaction (51.3 %), pharmacokinetics (36.3 %) and revision date of the information (21.0 %). Conclusion: This study reveals that advertising materials used in promoting drugs in Nigeria have incomplete information ...

  12. Application of RPMI 2650 as a cell model to evaluate solid formulations for intranasal delivery of drugs.

    Science.gov (United States)

    Gonçalves, Vanessa S S; Matias, Ana A; Poejo, Joana; Serra, Ana T; Duarte, Catarina M M

    2016-12-30

    During the development of intranasal drug delivery systems for local/systemic effect or brain targeting, it is necessary to assess its cytotoxicity and drug transport through nasal epithelium. In order to avoid animal experiments or the use of excised tissues, in vitro cell models, such as RPMI 2650 cells, are being preferred during recent years. Nevertheless, the deposition of solid formulations into nasal cell layers with further transepithelial transport rate of drugs has been poorly studied or reported. Thus, the purpose of this work is to further investigate RPMI 2650 cell line as an effective alternative to animal tissues for solid drug-loaded formulations cytotoxicity and drug permeation studies in order to become an option as a tool for drug discovery. Furthermore, we wanted to determine the extent to which the administration of drugs in particulate forms would differ in relation to the permeability of the same compounds applied as solutions. RPMI 2650 cells were cultured in submersed or at air-liquid interface conditions and characterized regarding transepithelial electrical resistance (TEER) and production of mucus. Pure ketoprofen (used as model compound) and five formulations loaded with same drug, namely solid lipid particles (Gelucire 43/01™), structured lipid particles (Gelucire 43/01™:Glyceryl monooleate) and aerogel microparticles (Alginate, Alginate:Pectin, Alginate:Carrageenan), were evaluated with RPMI 2650 model in terms of cytotoxicity and permeability of drug (applied as solution, dispersion or powder+buffer). RPMI 2650 cells were capable to grow in monolayer and multilayer, showing the same permeability as excised human nasal mucosa for sodium fluorescein (paracellular marker), with analogous TEER values and production of mucus, as referred by other authors. None of the powders showed cytotoxicity when applied to RPMI 2650 cells. Regarding permeation of drug through cell layers, not only the form of application of powders but also their

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

    Science.gov (United States)

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

    2017-09-01

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

  14. Evaluating the Implementation of Drug Decriminalization in Tijuana Mexico: Police and Public Health

    OpenAIRE

    Arredondo Sanchez Lira, Jaime

    2017-01-01

    This research seeks to evaluate the impact of drug policy reform in Mexico within the larger Latin American context. Through theoretical and statistical analyses, I use the case study of the municipal Police Department in Tijuana to understand the implementation of Mexico’s 2009 “narcomenudeo” drug policy reform that decriminalized drug possession for personal consumption. Using internal unpublished police data, I demonstrate that the policy shift did not appear to impact the policing of drug...

  15. 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

  16. An evaluation of Access Tier local area network switches.

    Energy Technology Data Exchange (ETDEWEB)

    Eldridge, John M.; Olsberg, Ronald R.

    2004-06-01

    This reports tabulates the Test and Evaluation results of the Access Class Switch tests conducted by members of Department 9336. About 15 switches were reviewed for use in the enterprise network as access tier switches as defined in a three tier architecture. The Access Switch Tier has several functions including: aggregate customer desktop ports, preserve and apply QoS tags, provide switched LAN access, provide VLAN assignment, as well as others. The typical switch size is 48 or less user ports. The evaluation team reviewed network switch evaluation reports from the Tolly Group as well as other sources. We then used these reports as a starting point to identify particular switches for evaluation. In general we reviewed the products of dominant equipment manufacturers. Also, based on architectural design requirements, the majority of the switches tested were of relatively small monolithic unit variety.

  17. Evaluating the Importance of Local Environment on Tree Structural Allometries

    Science.gov (United States)

    Duncanson, L.; Cook, B. D.; Rourke, O.; Hurtt, G. C.; Dubayah, R.

    2013-12-01

    Allometric relationships relating various forest structural properties such as DBH, tree height and aboveground biomass have been developed through detailed field data collection both in the United States, and globally. However, there has been limited attention to explaining observed variability in these relationships. Often, a single relationship is developed for a single species, and is applied irrespective of environment. In this research, we attempt to explain allometry as a function of environment by focusing on the relationship between DBH, crown radius and tree height. Two primary datasets are used to conduct this research. First, the Forest Inventory Analysis (FIA) dataset, including tree DBH and height information for the United States, are used to investigate variability in the relationship between DBH and tree height. Second, high-resolution airborne lidar datasets were collected from areas across the US, Canada and Costa Rica and are applied to investigate variability in the relationship between crown radius and height. The lidar datasets are run through a generalized canopy delineation algorithm to produce multilayered estimates of individual tree location, height, and crown radius. Power law functions are fit to the relationships between DBH and tree height, and crown radius and tree height. The mean and standard deviation of the power law exponents are compared to environmental attributes including precipitation, temperature, topography, and age since disturbance. This research demonstrates that although universal tendencies are observed in average power law exponents, considerable local variability exists that can be partially attributed to local environment. Therefore local environment, as well as tree species, should be accounted for in the development and application of allometric equations for forest studies.

  18. 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

  19. 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

  20. 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]/ki 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'.

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

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    Specific delivery of drugs to diseased sites in the body is a major topic in the development of drug delivery system today. Especially, the field of cancer treatment needs improved drug delivery systems as the strong dose-limiting side effects of chemotherapy today often present a barrier...... unloading of the encapsulated drug have been tried optimized in a variety of ways. Many propose the use of small molecules, such as vitamins and peptides, for active targeting of the liposomes to overexpressed receptors on the cancerous tissue. Once located close to the diseased site a trigger mechanism...... 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...

  2. Ultrasound biomicroscopic localization and evaluation of intraocular foreign bodies.

    Science.gov (United States)

    Laroche, D; Ishikawa, H; Greenfield, D; Liebmann, J M; Ritch, R

    1998-08-01

    To evaluate the ultrasound biomicroscopic appearance of anterior segment foreign bodies under clinical and experimental conditions. Ultrasound biomicroscopy was performed on 4 eyes of 4 patients referred for evaluation of anterior segment trauma and known or suspected intraocular foreign body. Imaging of wood, aluminum, concrete, and glass foreign bodies was performed in the anterior chamber of a human cadaver eye. Ultrasound biomicroscopy verified the location of a foreign body in two patients and identified occult foreign bodies in two others. Under clinical and experimental conditions, intraocular aluminum and glass produced comet tail artifacts. Under experimental conditions intraocular wood and concrete produced shadowing artifacts. Ultrasound biomicroscopy provides useful information in the evaluation of known and occult anterior segment foreign bodies. Ultrasound patterns of shadowing and comet tail may help differentiate foreign body materials.

  3. Reasons for Change of Anti-Retroviral Therapy (ART) Drugs: Local ...

    African Journals Online (AJOL)

    Background: Highly active anti-retroviral therapy (HAART) reduces morbidity and mortality in HIV/AIDS infected patients. HAART is used indefinitely and the regimens are changed over the course of treatment due to resistance, adverse drug reactions or access to drugs. Few studies have been done in resource constrained ...

  4. Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

    OpenAIRE

    Negus, S. Stevens; Miller, Laurence L.

    2014-01-01

    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...

  5. Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs

    Directory of Open Access Journals (Sweden)

    Cardelli Pierluigi

    2011-09-01

    Full Text Available Abstract Background Cancer is one of the most difficult current health challenges, being responsible for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach, and the prevailing orientation calls for the administration of the maximum tolerated dose; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. Electrochemotherapy (ECT is a tumor treatment that combines the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses. In this article we evaluate the capability of ECT to allow the use of cisplatin despite its high toxicity in a spontaneous feline model of soft tissue sarcoma. Methods A cohort of sixty-four cats with incompletely excised sarcomas were treated with cisplatin-based adjuvant ECT and monitored for side effects. Their response was compared to that of fourteen cats treated with surgery alone. Results The toxicities were minimal and mostly treated symptomatically. ECT resulted in increased local control (median not reached at the time of writing with a mean time to recurrence of 666 days versus 180 of controls. Conclusions We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols.

  6. Evaluation of Electroencephalography Source Localization Algorithms with Multiple Cortical Sources.

    Directory of Open Access Journals (Sweden)

    Allison Bradley

    Full Text Available Source localization algorithms often show multiple active cortical areas as the source of electroencephalography (EEG. Yet, there is little data quantifying the accuracy of these results. In this paper, the performance of current source density source localization algorithms for the detection of multiple cortical sources of EEG data has been characterized.EEG data were generated by simulating multiple cortical sources (2-4 with the same strength or two sources with relative strength ratios of 1:1 to 4:1, and adding noise. These data were used to reconstruct the cortical sources using current source density (CSD algorithms: sLORETA, MNLS, and LORETA using a p-norm with p equal to 1, 1.5 and 2. Precision (percentage of the reconstructed activity corresponding to simulated activity and Recall (percentage of the simulated sources reconstructed of each of the CSD algorithms were calculated.While sLORETA has the best performance when only one source is present, when two or more sources are present LORETA with p equal to 1.5 performs better. When the relative strength of one of the sources is decreased, all algorithms have more difficulty reconstructing that source. However, LORETA 1.5 continues to outperform other algorithms. If only the strongest source is of interest sLORETA is recommended, while LORETA with p equal to 1.5 is recommended if two or more of the cortical sources are of interest. These results provide guidance for choosing a CSD algorithm to locate multiple cortical sources of EEG and for interpreting the results of these algorithms.

  7. Roundness deviation evaluation method based on statistical analysis of local least square circles

    Science.gov (United States)

    Zhi-min, Cao; Yun, Wu; Jian, Han

    2017-10-01

    Today, the quantitative evaluation of the quality of circular or cylindrical workpieces is becoming increasingly important for the relevant industrial production sectors. Although there are already some roundness deviation evaluation algorithms available to accomplish this task, these methods are always done in a holistic way. In many industrial scenarios, however, fine evaluation of the roundness variation of local segments is often more practical than the global assessment. By performing a fine evaluation of roundness variation of local segments, crucial information that can reveal intrinsic quality characteristics of both the workpiece and the production machine can be retrieved. However, this important issue has not been well studied. To deal with this problem, a roundness deviation evaluation method based on statistical analysis of local least square circles was proposed. Experimental results illustrated that the proposed method can stably and reliably evaluate the local and global roundness deviations effectively.

  8. Environmental risk: perception and target with local versus global evaluation.

    Science.gov (United States)

    Fleury-Bahi, Ghozlane

    2008-02-01

    This research addressed environmental risk perception depending on the target evaluated and on the category of hazard (technological and chemical hazards, climate change, loss of biodiversity). Correlations between environmental risk assessment and pro-environmental behavioural intentions were also tested. In a sample of 113 French adults, 15 different environmental risks were evaluated for four different risk targets (oneself, the inhabitants of the town, the inhabitants of the country, and humanity). As expected, environmental hazards were perceived as a greater risk for larger areas. Moreover, risks difficult to conceptualise, which contain both high uncertainty and long-term consequences (climate change, loss of biodiversity) are perceived as less risk to oneself and to the inhabitants of the town and the country of residence than more concrete and immediate risks (technological and chemical). Only the technological and chemical hazards significantly predict pro-environmental behavioural intentions.

  9. Social Economy for Local Governance Structures: Monitoring and Evaluation Perspectives

    OpenAIRE

    Nasioulas, Ioannis; Tsobanoglou, George

    2006-01-01

    Social economy , the ground between free market private benefit institutions , the State regulation and society , needs to be positively identified. The existing , traditional , monitoring and evaluation concepts , methods and tools are prooven to ineffectively identify and describe the social conjunctions , adherent to the social mediation of the economic sphere. Coherent , scientifically valid , approaches need to be formulated. Up to date methods and tools , capable of reaching and describ...

  10. Evaluation of Local Flow Conditions in Jailed Side Branch Lesions Using Computational Fluid Dynamics

    OpenAIRE

    Na, Sang-Hoon; Koo, Bon-Kwon; Kim, Jeong Chul; Yang, Han-Mo; Park, Kyung-Woo; Kang, Hyun-Jae; Kim, Hyo-Soo; Oh, Byung-Hee; Park, Young-Bae

    2011-01-01

    Background and Objectives Lesions of vascular bifurcation and their treatment outcomes have been evaluated by anatomical and physiological methods, such as intravascular ultrasound and fractional flow reserve (FFR). However, local changes in flow dynamics in lesions of bifurcation have not been well evaluated. This study aimed at evaluating changes in the local flow patterns of bifurcation lesions. Materials and Methods Eight (n=8) representative simulation-models were constructed: 1 normal b...

  11. 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.

  12. 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.

  13. Evaluation of Giardia lamblia thioredoxin reductase as drug activating enzyme and as drug target.

    Science.gov (United States)

    Leitsch, David; Müller, Joachim; Müller, Norbert

    2016-12-01

    The antioxidative enzyme thioredoxin reductase (TrxR) has been suggested to be a drug target in several pathogens, including the protist parasite Giardia lamblia. TrxR is also believed to catalyse the reduction of nitro drugs, e.g. metronidazole and furazolidone, a reaction required to render these compounds toxic to G. lamblia and other microaerophiles/anaerobes. It was the objective of this study to assess the potential of TrxR as a drug target in G. lamblia and to find direct evidence for the role of this enzyme in the activation of metronidazole and other nitro drugs. TrxR was overexpressed approximately 10-fold in G. lamblia WB C6 cells by placing the trxR gene behind the arginine deiminase (ADI) promoter on a plasmid. Likewise, a mutant TrxR with a defective disulphide reductase catalytic site was strongly expressed in another G. lamblia WB C6 cell line. Susceptibilities to five antigiardial drugs, i.e. metronidazole, furazolidone, nitazoxanide, albendazole and auranofin were determined in both transfectant cell lines and compared to wildtype. Further, the impact of all five drugs on TrxR activity in vivo was measured. Overexpression of TrxR rendered G. lamblia WB C6 more susceptible to metronidazole and furazolidone but not to nitazoxanide, albendazole, and auranofin. Of all five drugs tested, only auranofin had an appreciably negative effect on TrxR activity in vivo, albeit to a much smaller extent than expected. Overexpression of TrxR and mutant TrxR had hardly any impact on growth of G. lamblia WB C6, although the enzyme also exerts a strong NADPH oxidase activity which is a source of oxidative stress. Our results constitute first direct evidence for the notion that TrxR is an activator of metronidazole and furazolidone but rather question that it is a relevant drug target of presently used antigiardial drugs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Evaluation of dibutyrylchitin as new excipient for sustained drug release.

    Science.gov (United States)

    Casettari, Luca; Cespi, Marco; Castagnino, Enzo

    2012-08-01

    Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and (1)H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.

  15. In situ epicatechin-loaded hydrogel implants for local drug delivery ...

    African Journals Online (AJOL)

    -inflammatory, and neuroprotective tea flavonoid, and characterise them in situ as a vehicle for prolonged and safer drug delivery in patients with post-traumatic spinal cord injury. Methods: Five in situ gel formulations were prepared using ...

  16. The Limits of the Czar’s Ukase: Drug Policy at the Local Level

    Science.gov (United States)

    1990-06-01

    aftercare programs, adolescent and adult-oriented programs, and other programs. Where HIV infection has spread to a significant percentage of the IVDA...recidivism. cooperation among treat ment and correct ions agencies wil haet-buh more efl ’ ctive than it was during pre- vious drug abuse epidemics. 2...commnunity-%wide program to prevent use. of, alcohol and( other drugs by young adolescents Iin the Kansas (ivarea. auined at both inner city and

  17. An outpatient drug program for adolescent students: preliminary evaluation.

    Science.gov (United States)

    Gottheil, E; Rieger, J A; Farwell, B; Lieberman, D

    1977-01-01

    Adolescent students with drug problems were rostered by their schools at the program facility one-half day per week. Treatment was aimed at increasing communicativeness through art, video, music, group therapy, and individual counseling when appropriate. After 4 months, school personnel, students, and treatment staff indicated that drug taking had decreased and general adjustment improved. Statistically, the treatment group (N = 42) improved significantly more than a control group (N = 37) in school attendance. They also tended to do better in academic, behavior, and work habit grades although these differences did not reach statical significance. Further similar early intervention studies are warranted.

  18. Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

    Science.gov (United States)

    Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

    2014-03-01

    Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    African Journals Online (AJOL)

    Purpose: To determine the prevalence of drug therapy problems (DTPs), identify the types of DTPs and assess outcomes of DTP interventions among renal patients receiving care in three Nigerian tertiary hospitals. Methods: This prospective descriptive study was conducted in nephrology units of three tertiary hospitals in ...

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

    African Journals Online (AJOL)

    Prescriptions were examined for order, number, and therapeutic class of drugs in addition to poly-pharmacy and appropriateness. Patients having ... Conclusion: Prescription pattern was mainly in accordance with standard guidelines with some knowledge and technical gaps in prescription writing methodology. Keywords: ...

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

    African Journals Online (AJOL)

    The concentration of ciprofloxacin hydrochloride tablets in the Nigerian market was analyzed using both back-titration and UV-visible spectrophotometric methods. The results obtained showed that different brands contained different concentrations of the drug; some brands contained lower concentrations while others were ...

  2. Sex Stereotyping in Drug Advertisements: Evaluation of the Informal Curriculum.

    Science.gov (United States)

    Wolfe, Mary L.; And Others

    A study to determine sex stereotyping in drug advertisements in five professional journals is reported. The first four studies examined advertisements from general medical journals; the fifth study obtained its data from a psychiatric journal. The journals are "Medical Economics,""American Family Physician,""Modern Medicine,""Journal of the…

  3. Evaluation of the adverse drug reaction surveillance system ...

    African Journals Online (AJOL)

    Results: The surveillance system did not meet up to its objectives as it failed to detect the adverse drug reactions and there was no monitoring of increases in known events. Fewer than half (43%) of the participants were aware of at least 2 objectives of the surveillance system but 83% of health workers willing to participate.

  4. Evaluating adverse drug reactions among HAART patients in a ...

    African Journals Online (AJOL)

    The high prevalence of HIV in KwaZulu-Natal Province, South Africa, has greatly increased the demand for antiretroviral therapy (ART), resulting in an exponential increase in the number of patients initiated on highly active antiretroviral treatment (HAART). However, little information about adverse drug reactions in these ...

  5. Evaluation of Drug Load and Polymer by Using a 96-Well Plate Vacuum Dry System for Amorphous Solid Dispersion Drug Delivery

    National Research Council Canada - National Science Library

    Chiang, Po-Chang; Ran, Yingqing; Chou, Kang-Jye; Cui, Yong; Sambrone, Amy; Chan, Connie; Hart, Ryan

    2012-01-01

    .... A minimal amount of drug was required to evaluate optimal drug load in three different polymers with respect to solubility improvement and solid-state stability of the amorphous drug–polymer system...

  6. The evaluation of drug provocation tests in pediatric allergy clinic: a single center experience.

    Science.gov (United States)

    Vezir, Emine; Erkocoglu, Mustafa; Civelek, Ersoy; Kaya, Aysenur; Azkur, Dilek; Akan, Aysegül; Ozcan, Celal; Toyran, Muge; Ginis, Tayfur; Misirlioglu, Emine Dibek; Kocabas, Can Naci

    2014-01-01

    Drug provocation tests (DPTs) are gold standard to diagnose drug allergy. Our goal was to evaluate the results and safety of diagnostic methods including DPTs during childhood. Between January 2010 and February 2013 DPTs were performed and evaluated, prospectively, in children who attended our pediatric allergy clinic with a suspected drug hypersensitivity reaction. One hundred ninety-eight suspected drug reactions in 175 patients (88 boys and 87 girls) were evaluated. The median age of the subjects at the time of the suspected drug-induced hypersensitivity reaction and at the time of the study was 56 (interquartile range [IQR] = 24-120 months) months and 76 (IQR = 35-149 months) months, respectively. Suspected drugs were beta-lactam antibiotics in 108 cases (54.5%), non-beta-lactam antibiotics in 22 cases (11.1%), and nonsteroid anti-inflammatory drugs in 52 cases (26.3%). The history was compatible with immediate-type reactions in 69 cases (34.8%). Skin-prick tests were not positive in any of the cases. Intradermal tests were positive in three cases (4%). DPTs were positive in 13 (6.8%) of 191 provocation cases, which were performed with culprit drugs. Our results suggest that a positive clinical history is not enough to make a diagnosis of drug allergy, which highlights the significance of undertaking further diagnostic evaluation especially for DPTs.

  7. 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

  8. Melt-spun bioactive sutures containing nanohybrids for local delivery of anti-inflammatory drugs.

    Science.gov (United States)

    Catanzano, Ovidio; Acierno, Stefano; Russo, Pietro; Cervasio, Mariarosaria; Del Basso De Caro, Marialaura; Bolognese, Adele; Sammartino, Gilberto; Califano, Luigi; Marenzi, Gaetano; Calignano, Antonio; Acierno, Domenico; Quaglia, Fabiana

    2014-10-01

    In this work, a novel concept is introduced in drug-eluting fibres to ensure a good control of drug delivery features and wide applicability to different bioactive compounds. Composite bioactive sutures based on fibre grade poly(ε-caprolactone) (PCL) and loaded with the anti-inflammatory drug Diclofenac (Dic) or a Dic nanohybrid where the drug is intercalated in a synthetic hydrotalcite (Mg/Al hydroxycarbonate) (HT-Dic) were developed. Fibres were prepared by melt-spinning at different PCL/HT-Dic/Dic ratios and analysed in terms of morphology, mechanical properties and drug release features. Results emphasized that tensile properties of fibres are clearly affected by Dic or HT-Dic addition, while the presence of knots has limited influence on the mechanical behaviour of the sutures. Release of Dic strongly depends on how Dic is loaded in the fibre (as free or nanohybrid) whereas the combination of free Dic and HT-Dic can allow a further tuning of release profile. In vivo experiments show a reduction of inflammatory responses associated with Dic-loaded fibers. Thus, a proof of principle is provided for a novel class of bioactive sutures integrating advanced controlled-release technologies. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Evaluation and registration of adverse events in clinical drug trials in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, P.; Bjarnason, N.H.; Dahlof, C.

    2008-01-01

    Tolerability of a drug should be regarded as important as its efficacy. In all four phases of drug development evaluation of adverse events is important. Recommendations for assessment of adverse events in acute and prophylactic clinical drug trials in migraine are given. Tolerability may be indi...... be indirectly assessed using measures of general well-being and eight such tools are presented. Finally, recommendations for reporting of adverse events are given Udgivelsesdato: 2008/7......Tolerability of a drug should be regarded as important as its efficacy. In all four phases of drug development evaluation of adverse events is important. Recommendations for assessment of adverse events in acute and prophylactic clinical drug trials in migraine are given. Tolerability may...

  10. 77 FR 69634 - Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing...

    Science.gov (United States)

    2012-11-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals; Availability AGENCY: Food and Drug Administration, HHS. ACTION... industry 217 entitled ``Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals...

  11. 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.

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

    OpenAIRE

    Padma Rao Pogaku; Subramanian Palani; Sudhakar Penthala; P Sreeman Narayana; Nagaraju Mukkamula

    2017-01-01

    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. canaden...

  13. 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.

  14. Hypersensitive reactions to local dental anesthetics and patient information: critical review of a drug leaflet

    Directory of Open Access Journals (Sweden)

    Simonet D

    2011-09-01

    Full Text Available Daniel Simonet School of Business and Management, American University of Sharjah, Sharjah, United Arab Emirates Abstract: This paper discusses the case of a patient who experienced adverse reactions to a local anesthetic. It reviews symptoms of adverse reactions, possible causes, patient management, and alternative anesthesia modes. The second part of the paper discusses the product leaflet information and the associated legal issues. Keywords: hypersensitive reactions, local dental anesthetics, patient information

  15. Evaluating the molecule-based prediction of clinical drug responses in cancer.

    Science.gov (United States)

    Ding, Zijian; Zu, Songpeng; Gu, Jin

    2016-10-01

    Molecule-based prediction of drug response is one major task of precision oncology. Recently, large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), provide the opportunity to evaluate the predictive utility of molecular data for clinical drug responses in multiple cancer types. Here, we first curated the drug treatment information from TCGA. Four chemotherapeutic drugs had more than 180 clinical response records. Then, we developed a computational framework to evaluate the molecule based predictions of clinical responses of the four drugs and to identify the corresponding molecular signatures. Results show that mRNA or miRNA expressions can predict drug responses significantly better than random classifiers in specific cancer types. A few signature genes are involved in drug response related pathways, such as DDB1 in DNA repair pathway and DLL4 in Notch signaling pathway. Finally, we applied the framework to predict responses across multiple cancer types and found that the prediction performances get improved for cisplatin based on miRNA expressions. Integrative analysis of clinical drug response data and molecular data offers opportunities for discovering predictive markers in cancer. This study provides a starting point to objectively evaluate the molecule-based predictions of clinical drug responses. jgu@tsinghua.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation.

    Science.gov (United States)

    Babiskin, Andrew H; Zhang, Xinyuan

    2015-09-01

    Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used for the treatment of attention deficit hyperactivity disorder. We developed physiologically based absorption models for mixed AMP salts ER capsules and dextroamphetamine sulfate ER capsules to address specific questions raised during generic drug postmarketing surveillance and bioequivalence (BE) guidance development. The models were verified against several data sets. Virtual BE simulations were conducted to assess BE in various populations other than normal healthy subjects where BE studies are generally conducted for approval. The models were also used to predict pharmacokinetics (PK) for hypothetical formulations having dissolution profiles falling within specification after the development of in vitro-in vivo relation. Finally, we demonstrated how to use the models to test sensitivity of PK metrics to the changes in formulation variables. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  17. Current Status of the Matson Evaluation of Drug Side Effects (MEDS)

    Science.gov (United States)

    Matson, Johnny L.; Cervantes, Paige E.

    2013-01-01

    The Matson Evaluation of Drug Side Effects (MEDS) is currently the best established and most researched measure of drug side effects in the intellectual disability (ID) literature. Initial research was conducted on its psychometric properties such as reliability and validity. More recent research studies have used the measure to determine the…

  18. An Evaluation of an Innovative Drug Education Program: First Year Results.

    Science.gov (United States)

    Schaps, Eric; And Others

    An innovative drug education course was taught to seventh and eighth graders and evaluated in a true experiment. Students learned Lasswell's framework for understanding human needs and motives, a systematic decision-making procedure, and information about the pharmacological, psychological, and social consequences of licit and illicit drug use.…

  19. Evaluation of a Court-Ordered MADD Presentation for Juvenile Alcohol and Drug Offenders

    Science.gov (United States)

    Theriot, Matthew T.

    2006-01-01

    This study evaluates the effectiveness of a court-ordered Mothers Against Drunk Driving (MADD) presentation to prevent alcohol or drug-related recidivism among 247 juvenile alcohol and drug offenders. The presentation, which incorporates educational components with a victim awareness program, seeks to increase offenders' empathy and knowledge…

  20. Sequential alterations in the micro-localization of catalase in mouse liver after treatment with hypolipidemic drugs.

    Science.gov (United States)

    Klucis, E; Crane, D; Masters, C

    1984-11-01

    A comparative study has been carried out on the micro-localization of catalase in mouse tissues subsequent to treatment with a representative range of hypolipidemic drugs. A commonality of effect was shown by clofibrate (ethyl-alpha-p-chlorophenoxyisobutyrate), Wy-14,643 (4-chloro-6-[2,3 xylidino)-2-pyrimidinylthio] acetic acid), RMI-15,414 (5-tetradecyloxy-2-furancarboxylic acid) and aspirin (acetyl salicylic acid), in that treatments with each of these drugs was associated with the release of peroxisomal catalase into the cytoplasmic compartment of liver and kidney. It was also noticeable that this increased cytosolic activity was characterized by the presence of an 'aged' form of the enzyme with different mobility and activity characteristics to that of the peroxisomal enzyme. Possible molecular bases for these effects and their relationship to peroxisomal biogenesis are discussed.

  1. [Evaluation of the carbohydrate metabolism in the drug addict].

    Science.gov (United States)

    Arnalich, F; Monereo, A; Arribas, J R; Grande, C; Camacho, J; Barbado, F J; Vázquez, J J

    1989-04-01

    A prospective study to determine the carbohydrate metabolism in 23 intravenous drug users (IVDU) was carried out. 13 of them had no infection complications (group A), while the other 10 had acute associated infectious (group B). Both groups showed basal glycemia, insulin and glycosylated hemoglobin levels, similar to the control determinations. There were no correlations between these parameters and the hepatic function test alterations or the immunological changes in the IVDU. Our results showed that there were no alterations in the carbohydrates metabolism of the IVDU with a normal nutritional state, in spite of the well-known hypoglycemic effects of opiates in the experimental animal mode.

  2. Drug and Vaccine Evaluation in the Human Aotus Plasmodium Falciparum Model

    National Research Council Canada - National Science Library

    Obaldia

    2002-01-01

    The purpose of this report is to present data on the evaluation of drugs and vaccines in the human malaria/Aotus lemurinus lemurinus monkey model experimentally infected with Plasmodium falciparum or vivax...

  3. Evaluation of Student Learning in a Nonprescription Drug Course without Examinations.

    Science.gov (United States)

    Popovich, Nicholas G.; VanVeldhuizen-Scott, Meri Kay

    1994-01-01

    A pharmacy course in nonprescription drugs in which student evaluation was based on homework assignments, written reflective paragraphs, and class attendance but not examinations was seen by students as enhancing their personal sense of responsibility for learning. (Author/MSE)

  4. Evaluation of the potential for pharmacokinetic drug-drug interaction between armodafinil and carbamazepine in healthy adults.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Yang, Ronghua; Hellriegel, Edward T; Robertson, Philmore

    2015-02-01

    Polypharmacy is common in psychiatry practice and can lead to an increased risk of drug interactions. Armodafinil, a wakefulness-promoting agent, has been studied as adjunctive therapy for the treatment of major depressive episodes associated with bipolar I disorder. Armodafinil and the mood stabilizer carbamazepine are both inducers of and substrates for cytochrome P450 (CYP3A4). This study was designed to evaluate the bidirectional carbamazepine-armodafinil pharmacokinetic drug-drug interaction. This was an open-label, single-center study conducted in healthy adult men. Subjects assigned to group 1 received a dose of carbamazepine (200 mg) alone and a dose after pretreatment with daily dosing of armodafinil (titrated to 250 mg/d). Subjects assigned to group 2 received a dose of armodafinil (250 mg) alone and a dose after pretreatment with carbamazepine BID (titrated to 400 mg/d). Pharmacokinetic parameters for carbamazepine, armodafinil, and their major circulating metabolites were determined when dosed alone and after pretreatment with the other drug. The safety and tolerability of armodafinil and carbamazepine were also assessed throughout the study. Eighty-one subjects enrolled in the study (group 1 = 40; group 2 = 41), of whom 79 (group 1 = 40; group 2 = 39) were evaluable for pharmacokinetic analysis and 80 (group 1 = 40; group 2 = 40) were evaluable for safety analysis. In group 1, pretreatment with armodafinil reduced systemic exposure to carbamazepine by 12% for Cmax and 25% for AUC (based on comparison of geometric means). Similarly, in group 2, pretreatment with carbamazepine reduced systemic exposure to armodafinil by 11% for Cmax and 37% for AUC. Systemic exposure to the metabolites of these agents that are formed via CYP3A4 were increased after pretreatment in each group. There were no new or unexpected adverse events. Systemic exposure to both carbamazepine and armodafinil was reduced after pretreatment with the other drug; systemic exposure to the

  5. Evaluation of food-drug interaction of guava leaf tea.

    Science.gov (United States)

    Kaneko, Kimiyuki; Suzuki, Katsuya; Iwadate-Iwata, Emi; Kato, Ikuo; Uchida, Kazumi; Onoue, Masaharu

    2013-02-01

    Guava leaf tea (GLT) contains guava leaf polyphenol (Gvpp), which regulates the absorption of dietary carbohydrate from the intestines. Borderline diabetics, who are at high risk of development of diabetes, take GLT to suppress a rapid increase of blood sugar level after meals. However, patients with diabetes in whom diabetic drugs or warfarin as a blood thinner are prescribed also take GLT with the expectation of glycemic control. Therefore, we studied whether GLT had potential for inhibition or induction of cytochrome P450 (CYP) and an influence on the action of warfarin. Extract of guava leaf (GvEx) consists of carbohydrate and polyphenols, which are Gvpp, quercetin, and ellagic acid. These polyphenols, but not GvEx, showed a certain level of inhibition of human-cDNA-expressed CYPs. In a comparison of GLT and grapefruit juice, GLT showed weaker inhibition of CYP activities and of midazolam 1'-hydroxylation than grapefruit juice. Furthermore, neither liver weight nor CYP3A expression in the liver was changed in rats that received GvEx for 90 days compared with the control group. When rats were concomitantly treated with GLT and warfarin, the prolongation of clotting time of blood by warfarin was not influenced. These data suggest that GLT is unlikely to interact with drugs. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Drug safety evaluation of dronedarone in atrial fibrillation.

    Science.gov (United States)

    De Ferrari, Gaetano M; Dusi, Veronica

    2012-11-01

    Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 - 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.

  7. 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.

  8. In vitro evaluation of Moringa oleifera gum for colon-specific drug delivery.

    Science.gov (United States)

    Singhal, Anil Kumar; Jarald, Edwin E; Showkat, Ahmad; Daud, Anwar

    2012-01-01

    Moringa gum obtained from stem of the plant Moringa oleifera Lam. belonging to family Moringaceae. Number of naturally occurring polysaccharides obtained from plant (guar gum, inulin), animal (chitosan, chondrotin sulphate), algal (alginates) or microbial (dextran) origin. The present study was evaluated Moringa oleifera gum as a carrier for colon specific drug delivery using in vitro drug release studies. Six formulations of curcumin were prepared using varying concentration of Moringa oleifera gum containing 50 mg curcumin by wet granulation method. Tablets were subjected for evaluation by studying the parameter like hardness, friability, drug content uniformity and in vitro drug release study. Hardness was found to be in the range of 5.5 to 7.3 kg/cm(2), the percentage friability was in the range of 0.60 to 0.89%, and tablet showed 98.99% to 99.89% of the labeled amount of curcumin indicating uniformity in drug content. In vitro drug release study was performed using simulated stomach, intestinal and colonic fluid. The susceptibility of Moringa gum to colonic bacteria was also assessed using drug release study with rat caecal contents. 30% Moringa gum containing formulation (F-3) was shown better drug released that is 90.46%, at the end of 24 h of dissolution study in the presence of rat caecal contents in comparison to 40% Moringa gum containing formulation (F-4) that was 78.03%. The results illustrate the usefulness of Moringa olefera gum as a potential carrier for colon-specific drug delivery.

  9. Hypersensitive reactions to local dental anesthetics and patient information: critical review of a drug leaflet

    Science.gov (United States)

    Simonet, Daniel

    2011-01-01

    This paper discusses the case of a patient who experienced adverse reactions to a local anesthetic. It reviews symptoms of adverse reactions, possible causes, patient management, and alternative anesthesia modes. The second part of the paper discusses the product leaflet information and the associated legal issues. PMID:22915891

  10. 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…

  11. Examination of risk evaluation and mitigation strategies and drug safety in the US.

    Science.gov (United States)

    Rodriguez-Monguio, Rosa; Spielberger, Kerry; Seoane-Vazquez, Enrique

    2014-01-01

    The Food and Drug Administration Amendment Act of 2007 (FDAAA 2007) enabled the US Food and Drug Administration (FDA) to require risk evaluation and mitigation strategies (REMS) for a drug or biologic to ensure that its benefits outweigh the risks. This study sought to evaluate REMS approved and released by the FDA since the program inception in 2008, to assess the characteristics of REMS approved and to calculate the time lag between FDA drug application approval and REMS approval. Data were derived from Approved Drug Products with Therapeutic Equivalence Evaluations, Approved REMS and Drugs@FDA. Data included generic availability, application type and approval date, therapeutic class and FDA review class, orphan designation, priority review and market status. The FDA approved REMS for 259 marketing applications (217 new drug applications -NDAs, 10 abbreviated NDAs, and 32 biologic license applications) in the study period. The FDA granted orphan designation to 11.4% of active ingredients with REMS and priority review to 38.4% of the NDAs with REMS. The largest number of REMS approvals was for nervous system products (31.8% of total approved REMS) and antineoplastic and immunomodulating agents (15.3%). The FDA approved REMS for one in three biologics and one in thirteen chemical entities available in the market. A pharmaceutical product can be in the market for an average of 14 years before the FDA identifies and evaluates the risk problems that warrant the approval of a REMS. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. 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.

  13. 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.

  14. Perspective, Method, and Data Triangulation in the Evaluation of a Local Educational Landscape

    Directory of Open Access Journals (Sweden)

    Kristina Ackel-Eisnach

    2012-07-01

    Full Text Available Communal engagement and co-operation in the field of education has become increasing important in the last few years. The goal is to expand the local educational landscapes by improving the quality of the educational programs. Therefore responsibilities, networks and new-designed educational programs have to be enhanced. To control the efficiency of these arrangements and the budget, a lot of councils delegate experts to evaluate these new implementations. The following article describes the evaluation for the council Ulm. The program of the local educational landscape is known as "Bildungsoffensive Ulm." The evaluation presents methods such as triangulation of perspectives, mixed-method design and data triangulation. Following the local situation is presented and the methods applied in the evaluation are justified methodologically. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs120354

  15. The therapeutic index of locally acting inhaled drugs as a function of their fine particle mass and particle size distribution - A literature review

    NARCIS (Netherlands)

    Weda, Marjolein; Zanen, Pieter; De Boer, Anne H.; Barends, Dirk M.; Frijlink, Henderik W.

    2008-01-01

    The therapeutic index (TI) of locally acting inhaled drug products depends on a number of parameters and processes: the particle size distribution of the inhaled aerosol, the dose-efficacy response curves at the deposition sites, the amount of drug absorbed into the systemic circulation from the

  16. Evaluating adverse drug event reporting in administrative data from emergency departments: a validation study

    Science.gov (United States)

    2013-01-01

    Background Adverse drug events are a frequent cause of emergency department presentations. Administrative data could be used to identify patients presenting with adverse drug events for post-market surveillance, and to conduct research in patient safety and in drug safety and effectiveness. However, such data sources have not been evaluated for their completeness with regard to adverse drug event reporting. Our objective was to determine the proportion of adverse drug events to outpatient medications diagnosed at the point-of-care in emergency departments that were documented in administrative data. Methods We linked the records of patients enrolled in a prospective observational cohort study on adverse drug events conducted in two Canadian tertiary care emergency departments to their administrative data. We compared the number of adverse drug events diagnosed and recorded at the point-of-care in the prospective study with the number of adverse drug events recorded in the administrative data. Results Among 1574 emergency department visits, 221 were identified as adverse drug event-related in the prospective database. We found 15 adverse drug events documented in administrative records with ICD-10 codes clearly indicating an adverse drug event, indicating a sensitivity of 6.8% (95% CI 4.0–11.2%) of this code set. When the ICD-10 code categories were broadened to include codes indicating a very likely, likely or possible adverse event to a medication, 62 of 221 events were identifiable in administrative data, corresponding to a sensitivity of 28.1% (95% CI 22.3-34.6%). Conclusions Adverse drug events to outpatient medications were underreported in emergency department administrative data compared to the number of adverse drug events diagnosed and recorded at the point-of-care. PMID:24219303

  17. Evaluation of Anxiety and Depression Among Female Spouses of Iranian Male Drug Dependents

    Science.gov (United States)

    Noori, Roya; Jafari, Firoozeh; Moazen, Babak; Khoddami Vishteh, Hamid Reza; Farhoudian, Ali; Narenjiha, Hooman; Rafiey, Hassan

    2015-01-01

    Background: Existing evidences suggest the more vulnerability of spouses of drug dependents, in exposure to mental disorders. Objectives: This study aimed to evaluate the associated parameters of anxiety and depression among female spouses of male drug dependents. Patients and Methods: With a cross-sectional design in 2010, a total of 237 Iranian women were selected and divided into three groups: 1. non-drug-dependent wives who had non-drug-dependent husbands (Group I), 2. non-drug-dependent wives who had drug-dependent husbands (Group II), and 3. drug-dependent wives who had drug-dependent husbands (Group III). Socio-demographic characteristics were collected by a checklist, and the levels of anxiety and depression were measured through the Hospital Anxiety and Depression Scale (HADS). Linear regression was applied for determination of anxiety and depression predictors. Results: Mean age of the participants was about 35 years, and mean duration of marriage was 14 years. Drug dependence of the husband (P = 0.010) and lower monthly income of the family (P = 0.007) predicted the higher level of anxiety among the participants, while older age (P = 0.031), shorter marital duration (P = 0.016), and lower educational level (P = 0.045) in addition to spousal drug dependence (P = 0.023), and lower family income (P = 0.014) were significantly associated with higher levels of depression. Conclusions: Findings of the present study demonstrate that spousal drug dependence and lower monthly income were common predictors of anxiety and depression among spouses of drug dependents in Iran, while older age, shorter marital duration and lower educational level were predictors of depression. However, more research is needed to find casual relationships between spousal drug dependence and mental health in Iran. PMID:25861583

  18. Mesoporous silica/apatite nanocomposite: special synthesis route to control local drug delivery.

    Science.gov (United States)

    Sousa, A; Souza, K C; Sousa, E M B

    2008-05-01

    Synthetic hydroxyapatite is widely used in medicine and dentistry due its notable biocompatibility and bioactivity properties. The hydroxyapatite incorporation into silica has demonstrated excellent bioactivity or biodegradability, according to the content of calcium ions. Procedures to obtain ordered mesoporous silicates rely on the micelle-forming properties of a surfactant, whose chemical composition, size and concentration control the structural dimensions of the final material. This paper reports the synthesis of two types mesoporous materials: pure MCM-41 and a nanocomposite of apatite and mesoporous silica, MCM-41-HA. The samples were charged with atenolol as a model drug and in vitro release essays were carried out. The bioactivity behavior was investigated as a function of soaking time in simulated body fluid. The materials were characterized by X-ray diffraction, N2 adsorption, FTIR spectroscopy, scanning electron microscopy, dispersive energies spectroscopy, and transmission electron microscopy. The influence of the release rate of atenolol molecules from pure MCM-41 mesoporous and containing hydroxyapatite was demonstrated, since it results in a very slowly drug delivery from the nanocomposite system.

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

    Science.gov (United States)

    Ruggeri, Isabella; Bragato, Donatello; Colombo, Giorgio L; Valla, Emanuela; Di Matteo, Sergio

    2012-01-01

    Background 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 resources. This trend improved during the 3-year observation period. The mean annual cost per patient was higher for powders (€223.95) and sprays (€224.83) than for extrafine formulation (€142.71). Conclusion Based on this analysis, we suggest implementation of better health care planning and more appropriate prescription practices

  20. 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

  1. 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.

  2. Development and Evaluation of Amphotericin B Loaded Iron Oxide Nanoparticles for Targeted Drug Delivery to Systemic Fungal Infections

    Science.gov (United States)

    Balabathula, Pavan

    ) also had a sustained drug release profile up to 72 hours. The major mechanisms of drug release from these formulations were determined to be Fickian and non-Fickian diffusion with first order and Higuchi kinetic models as best fit. The cellular uptake profile for design D exhibited a time dependent uptake with maximum uptake at 0.5 and 4 hours for C. albicans and C. glabrata, respectively. All designs exhibited improved efficacy over AMB-D in the susceptibility testing conducted on clinical isolates of Candida. Design D was found to have an enhanced killing ability and was 16-25 fold more efficacious than AMB-D. An in vitro cellular association study found the uptake mechanism was energy dependent. An endocytosis inhibitor evaluation determined the major particle uptake pathway for C. albicans was lipid-raft mediated endocytosis, whereas for C. glabrata, it was clathrin-, caveolar-, and lipid-raft-mediated endocytosis. TEM and confocal images provided evidence the AMB-IONP were localized at or near the cell wall and membrane wall and inside the cytoplasm, nucleus and endolysosomal vesicles for tested isolates. The lyophilized formulation of AMB-IONP was successfully prepared using an appropriate amount (1:16 to the weight of IONP) of the lyoprotectant, sucrose. A short term stability study of both formulations (lyophilized and aqueous dispersion) at 5°C and 25°C for up to two months showed the lyophilized form was stable. In conclusion, a targeted nanotheronostic drug delivery system (AMB-IONP) was successfully designed, developed, characterized and evaluated as a potential drug product for IFIs treatment.

  3. An evaluation of methods for estimating the number of local optima in combinatorial optimization problems.

    Science.gov (United States)

    Hernando, Leticia; Mendiburu, Alexander; Lozano, Jose A

    2013-01-01

    The solution of many combinatorial optimization problems is carried out by metaheuristics, which generally make use of local search algorithms. These algorithms use some kind of neighborhood structure over the search space. The performance of the algorithms strongly depends on the properties that the neighborhood imposes on the search space. One of these properties is the number of local optima. Given an instance of a combinatorial optimization problem and a neighborhood, the estimation of the number of local optima can help not only to measure the complexity of the instance, but also to choose the most convenient neighborhood to solve it. In this paper we review and evaluate several methods to estimate the number of local optima in combinatorial optimization problems. The methods reviewed not only come from the combinatorial optimization literature, but also from the statistical literature. A thorough evaluation in synthetic as well as real problems is given. We conclude by providing recommendations of methods for several scenarios.

  4. Psyllium arabinoxylan: carboxymethylation, characterization and evaluation for nanoparticulate drug delivery.

    Science.gov (United States)

    Bhatia, Meenakshi; Ahuja, Munish

    2015-01-01

    The objective of present investigation was to optimize the interaction between carboxymethylated psyllium arabinoxylan and chitosan to prepare polyelectrolyte naoparticles for drug delivery applications. Arabinoxylan extracted from psyllium was carboxymethylated by reacting with monochloroacetic acid under alkaline conditions. Carboxymethylation of psyllium arabinoxylan was observed to increase its crystallinity, improve thermal stability and decrease the viscosity. Further, the effect of concentrations of carboxymethylated arabinoxylan and chitosan on the particle size and particle size distribution of ibuprofen loaded polyelectrolyte nanoparticles was screened using two-factor, three-level central composite experimental design. The results of optimization study revealed that the formation of nanometric polyelectrolyte is favored at the median level of carboxymethylated arabinoxylan and chitosan concentration. The optimal concentrations of carboxymethylated arabinoxylan and chitosan were found to be 0.0779% (w/v) and 0.0693% (w/v) respectively, which provided polyelectrolyte particles of size 337.2 nm and polydispersity index 0.335. Further, polyelectrolyte complex nanoparticles were found to release ibuprofen over a prolonged period of 10h following Higuchi's square root release kinetics with the mechanism of release being combination of diffusion and erosion of matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Drug evaluation studies in neonates: how to overcome the current limitations.

    Science.gov (United States)

    Allegaert, Karel; Smits, Anne; van den Anker, John

    2018-02-08

    Introduction Regulatory initiatives have stimulated drug research in infants, but the potential impact of drugs to improve health outcome in neonates remains underexplored. Areas covered In this review, we focus on current limitations in drug evaluation studies and how to overcome these. The low volume of studies has additional weaknesses such as single center studies, non-commercial sponsorship, overrepresentation of high postulated risk reductions, and underrepresentation of therapeutic exploratory studies. Master protocols and selection criteria for neonatal centers to participate in studies are useful to improve logistics related to performance. Limitations also relate to inaccurate assessment of drug effects (efficacy/safety). This is because of poor symptom recognition, case definitions, and suboptimal data on adverse drug reactions (ADRs) epidemiology. To overcome these limitations, it is necessary to develop core outcome sets, reference values, and specific ADR tools. The limitations identified and approaches suggested to improve drug evaluation are illustrated using neonatal abstinence syndrome as an example. Expert Commentary We anticipate to see an evolving neonatal clinical pharmacology discipline driven by neonatal pathophysiology and knowledge. Multidisciplinary collaborative efforts between health care providers, academia, pharmaceutical industry, advocacy groups and regulatory agencies are crucial to improve the impact of drug evaluation studies in neonates.

  6. Formulation and evaluation of bilayered gastroretentable mucoadhesive patch for stomach-specific drug delivery.

    Science.gov (United States)

    Pandey, Suneel; Jirwankar, Prachi; Mehta, Sandip; Pandit, Sachin; Tripathi, Pushpendra; Patil, Arun

    2013-08-01

    The aim of the present work was to develop and evaluate stomach-specific controlled release, gastroretentable mucoadhesive patch of lercanidipine HCl. This drug is essentially soluble in gastric pH range of 1- 4 and have a partition coefficient (log p-value) of 6.1; according to this concept, it has been decided to formulate the gastroretentive bioadhesive patch. The patch system consisted of a drug release rate controlling film, using the combination of Eudragit RSPO and RLPO; mucoadhesive film by using the combination of various hydrophilic polymers. Bilayered patch were made by using the selected batch of two films using the layering method and evaluated for the various parameters like in vitro swelling study, ex vivo mucoadhesive strength. Film was folded into a hard gelatin capsule, evaluated for in vitro drug release in pH 1.2 containing 0.2% (w/v) sodium lauryl sulphate (SLS), and in vivo bioavailability in rabbits. Patches could control the drug release up to 12 h, having mucoadhesion strength in the range of 4.05±0.4 N to 4.52±0.12 N. In vivo bioavailability results indicate that the gastroretentive patch system provides a novel way to retain the drug matrix for the longer period of time in a stomach, enhance drug absorption and thereby offer a promising strategy for gastroretentive mucoadhesive drug delivery for the lercanidipine HCl.

  7. 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.

  8. Evaluation of blood glucose in type II diabetic patients submitted to local anesthesia with different vasoconstrictors

    OpenAIRE

    MELLO, Renan Pollettini de; Ramacciato, Juliana Cama; PERUZZO, Daiane Cristine; Vicentini,Carllini Barroso; Bergamaschi,Cristiane de Cássia; Motta,Rogério Heládio Lopes

    2016-01-01

    ABSTRACT Objective: In the dental clinic, the use of local anesthetics containing vasoconstrictors in diabetic patients are still controversial raising some doubts. Thus, the objective of this randomized crossover clinical trial was to evaluate blood glucose, pulse oximetry and heart rate of type 2 diabetic patients when submitted to local anesthesia using prilocaine 3% associated to felypressin 0,03UI / ml (G1) and 2% lidocaine associated to epinephrine 1: 100,000 (G2). Methods: The sample...

  9. Evaluation of Range-based Methods for Localization in Grain Storages

    DEFF Research Database (Denmark)

    Juul, Jakob Pilegaard; Green, Ole; Jacobsen, Rune Hylsberg

    2016-01-01

    Monitoring biomass storages by using wireless sensor networks with localization capabilities can help prevent economic losses during storage, help to improve the grain quality and lower costs during drying. In this article, the received signal strength was used to perform localization of wireless......-field electromagnetic ranging were performed to evaluate the performance of the method. It was found that the experimental setup worked best between 2 - 7 m where the average error was 4.9% of the actual distance....

  10. 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

  11. 77 FR 35689 - Guidance for Industry on Irritable Bowel Syndrome-Clinical Evaluation of Drugs for Treatment...

    Science.gov (United States)

    2012-06-14

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Irritable Bowel Syndrome--Clinical Evaluation of Drugs for Treatment; Availability; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

  12. Evaluation of Gallium as a Tracer of Exogenous Hemoglobin-Haptoglobin Complexes for Targeted Drug Delivery Applications

    Science.gov (United States)

    Xu, Shengsheng; Kaltashov, Igor A.

    2016-12-01

    Haptoglobin (Hp) is a plasma glycoprotein that generates significant interest in the drug delivery community because of its potential for delivery of antiretroviral medicines with high selectivity to macrophages and monocytes, the latent reservoirs of human immunodeficiency virus. As is the case with other therapies that exploit transport networks for targeted drug delivery, the success of the design and optimization of Hp-based therapies will critically depend on the ability to accurately localize and quantitate Hp-drug conjugates on the varying and unpredictable background of endogenous proteins having identical structure. In this work, we introduce a new strategy for detecting and quantitating exogenous Hp and Hp-based drugs with high sensitivity in complex biological samples using gallium as a tracer of this protein and inductively coupled plasma mass spectrometry (ICP MS) as a method of detection. Metal label is introduced by reconstituting hemoglobin (Hb) with gallium(III)-protoporphyrin IX followed by its complexation with Hp. Formation of the Hp/Hb assembly and its stability are evaluated with native electrospray ionization mass spectrometry. Both stable isotopes of Ga give rise to an abundant signal in ICP MS of a human plasma sample spiked with the metal-labeled Hp/Hb complex. The metal label signal exceeds the spectral interferences' contributions by more than an order of magnitude even with the concentration of the exogenous protein below 10 nM, the level that is more than adequate for the planned pharmacokinetic studies of Hp-based therapeutics.

  13. 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 CH2 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.

  14. Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Baur J

    2016-06-01

    Full Text Available Johannes Baur,1 Christian O Ritter,2 Christoph-Thomas Germer,1 Ingo Klein,1 Ralph Kickuth,2 Ulrich Steger,1 1Department of General, Visceral, Vascular, and Pediatric Surgery, 2Institute of Radiology, University Hospital Würzburg, Würzburg, Germany Purpose: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE with drug-eluting beads (DEB-TACE is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE. Patients and methods: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. Results: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281. The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. Conclusion: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE. Keywords: transarterial chemoembolization, hepatocellular carcinoma, drug-eluting beads

  15. [Safety evaluation of anticancer drugs circuit in a regional hospital in Tunisia].

    Science.gov (United States)

    Sahli, Jihène; El Ghardallou, Meriam; Bougmiza, Iheb; Henchiri, Besma; Limam, Manel; Mejdoub, Rim; Mtiraoui, Ali; Ajmi, Thouraya

    2016-01-01

    Nowadays, the circuit of drugs is a plague. This situation may cause serious harm to patients. In this context, we conducted a study with the aim to describe and evaluate the circuit of anticancer drugs in a Tunisian regional hospital. This is an evaluative study of the risk of anticancer drugs, conducted over a period of 15 days during the year 2014 in the Department of Cancer Research of the Regional Hospital of Gafsa (Tunisia). The evaluation method is based on that conducted by the project "SECURIMED" and developed by the Coordination Committee of the Clinical Evaluation and Quality in Aquitaine (CCECQA) in France. In our study, the observation of anticancer drugs circuit has revealed some deficiencies. We noted that the roles of the various actors are subject sometimes to tasks shifting, which may sometimes be dangerous. The study also revealed a lack and an inadequacy with the standards in terms of the necessary equipment for the preparation of the anticancer drugs. Securing drugs circuit should be a priority included in all national processes and shared by all stakeholders to achieve a premium goal: the quality of care and patient safety.

  16. 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.

  17. [The history of developing anticancer Drugs and their evaluation guidelines in Japan].

    Science.gov (United States)

    Maeda, Hideki; Kurokawa, Tatsuo

    2014-01-01

    The cancer therapies currently available do not yet offer fully satisfactory treatments, even in 21st century, and efforts and progress are being made daily in the area of drug development. Anticancer drugs, which play the leading role in cancer therapy, are being developed dynamically around the world, and Japan is not an exception. Looking back on the history of developing anticancer drugs, cytotoxic drugs were the mainstream of drug development until the end of the 20th century. In the 21st century, they have been replaced by molecularly targeted drugs, and thus the development of cytotoxic drugs has been declining rapidly. There were various approaches to the development of anticancer drugs and clinical trial endpoints until the 1980s. In 1991, the "Guidelines for Clinical Evaluation Methods of Anti-Cancer Drugs in Japan" was issued. From 2000 onwards, there was vigorous discussion on the clinical trial endpoints of anticancer drugs in the United States. In conjunction with this discussion, the "Guidelines for Clinical Evaluation Methods of Anti-Cancer Drugs in Japan" was revised in 2005. The revised guidelines required survival data at the time of filing a new drug application (NDA) as a general rule. Around 2005, a bridging strategy was promoted as the "International Conference on Harmonization E5" was promulgated among Japan, the U.S. and EU, resulting in an outflow of clinical trials to overseas, with more non-Japanese survival data generated outside of Japan used for NDAs than Japanese data. Subsequently, the "Guideline for Basic Principles on Global Clinical Trials" was issued in 2007, which promoted the change in the mainstream approach from a bridging strategy to a pivotal, global study involving Japan. Thus, an era of full-fledged globalization in clinical trials began. We believe Japan will need systems to enhance the motivation for anticancer drug development, such as an expedited program or pediatric program, from now on. We hope that the

  18. Cell-penetrable lysine dendrimers for anti-cancer drug delivery: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Zhao, Jing; Zhou, Rui; Fu, Xiaoyu; Ren, Wen; Ma, Lifang; Li, Ran; Zhao, Yi; Guo, Li

    2014-07-01

    Improving the cell penetration and enhancing the cell selectivity of drugs have been approved for overcoming the major drawbacks of chemotherapeutic agents: the toxicity to normal cells and the drug resistance in tumors. In this paper, lysine dendrimers (G1-G3) were chosen as novel cell-penetrating carriers for anti-cancer drugs based on the internalization mechanism of cell-penetrating peptides and the characteristics of dendritic peptides. After labeling with fluorescein isothiocyanate (FITC), the cell-penetrable capacity of lysine dendrimers was certified by flow cytometric analysis. In a preliminary biological evaluation, the conjugates of lysine dendrimers and 5-fluorouracil showed the expected advantages: stable drug release, low toxicity to normal cells, and moderate inhibition of tumor cells. These results imply that cell-penetrable lysine dendrimers could be potential carriers in drug delivery of anti-cancer medicine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Evaluation of trypanocidal drugs used for human African trypanosomosis against Trypanosoma lewisi

    Science.gov (United States)

    Dethoua, Mariette; Nzoumbou-Boko, Romaric; Truc, Philippe; Daulouède, Sylvie; Courtois, Pierrette; Bucheton, Bruno; Cuny, Gérard; Semballa, Silla; Vincendeau, Philippe

    2013-01-01

    Trypanosomes from animals are potential pathogens for humans. Several human cases infected by Trypanosoma lewisi, a parasite of rats, have been reported. The number of these infections is possibly underestimated. Some infections were self-cured, others required treatment with drugs used in human African trypanosomosis. An in vitro evaluation of these drugs and fexinidazole, a new oral drug candidate, has been performed against T. lewisi in comparison with T. brucei gambiense. All have comparable activities against the two parasites. Suramin was not effective. In vivo, drugs were tested in rats immunosuppressed by cyclophosphamide. The best efficacy was obtained for fexinidazole, and pentamidine (15 mg/kg): rats were cured in 7 and 10 days respectively. Rats receiving nifurtimox-eflornithine combination therapy (NECT) or pentamidine (4 mg/kg) were cured after 28 days, while melarsoprol was weakly active. The identification of efficient drugs with reduced toxicity will help in the management of new cases of atypical trypanosomosis. PMID:24139487

  20. Evaluating local policy adoption campaigns in California: Tobacco Retail License (TRL) adoption.

    Science.gov (United States)

    Satterlund, Travis D; Treiber, Jeanette; Haun, Sue; Cassady, Diana

    2014-06-01

    As part of its state-wide "denormalization" campaign, the California Tobacco Control Program has funded local tobacco control projects to secure tobacco retail licenses (TRLs) in their communities. TRL policies generate funding by requiring tobacco retailers within a jurisdiction to obtain a license, which is in addition to the state license that tobacco retailers are legally required to purchase to sell tobacco products. The funding provided by TRLs enables local law enforcement to carry out inspection and enforcement operations. This paper examines the unique processes by which local project campaigns attempt to get TRL policies adopted in communities across the State of California. Twenty-two local projects submitted final evaluation reports pertaining to the adoption of TRLs, and the reports from these projects form the basis of the analysis. Successful campaigns tended to include the following strategies: (1) determining policy readiness; (2) gathering local data; (3) identifying and working with a "champion"; (4) building relationships with local law enforcement agencies and decision makers; and (5) educating community and decision makers. The major challenges faced by local projects included budget cuts and staffing issues, concern about creating an unfavorable environment for business by imposing more regulations and fees, and complaints about using law enforcement resources for tobacco control in light of more "pressing" public safety issues. These challenges proved difficult for local projects to overcome, and also highlight the need for projects to create and carry out strong but flexible tactical plans that incorporate the aforementioned strategies.

  1. Drug exposure in register-based research—An expert-opinion based evaluation of methods

    Science.gov (United States)

    Taipale, Heidi; Koponen, Marjaana; Tolppanen, Anna-Maija; Hartikainen, Sirpa; Ahonen, Riitta; Tiihonen, Jari

    2017-01-01

    Background In register-based pharmacoepidemiological studies, construction of drug exposure periods from drug purchases is a major methodological challenge. Various methods have been applied but their validity is rarely evaluated. Our objective was to conduct an expert-opinion based evaluation of the correctness of drug use periods produced by different methods. Methods Drug use periods were calculated with three fixed methods: time windows, assumption of one Defined Daily Dose (DDD) per day and one tablet per day, and with PRE2DUP that is based on modelling of individual drug purchasing behavior. Expert-opinion based evaluation was conducted with 200 randomly selected purchase histories of warfarin, bisoprolol, simvastatin, risperidone and mirtazapine in the MEDALZ-2005 cohort (28,093 persons with Alzheimer’s disease). Two experts reviewed purchase histories and judged which methods had joined correct purchases and gave correct duration for each of 1000 drug exposure periods. Results The evaluated correctness of drug use periods was 70–94% for PRE2DUP, and depending on grace periods and time window lengths 0–73% for tablet methods, 0–41% for DDD methods and 0–11% for time window methods. The highest rate of evaluated correct solutions for each method class were observed for 1 tablet per day with 180 days grace period (TAB_1_180, 43–73%), and 1 DDD per day with 180 days grace period (1–41%). Time window methods produced at maximum only 11% correct solutions. The best performing fixed method TAB_1_180 reached highest correctness for simvastatin 73% (95% CI 65–81%) whereas 89% (95% CI 84–94%) of PRE2DUP periods were judged as correct. Conclusions This study shows inaccuracy of fixed methods and the urgent need for new data-driven methods. In the expert-opinion based evaluation, the lowest error rates were observed with data-driven method PRE2DUP. PMID:28886089

  2. 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

  3. Drugs or disease: evaluating salivary function in RA patients

    Directory of Open Access Journals (Sweden)

    Sandra Regina TORRES

    Full Text Available Abstract Oral complications of RA may include temporomandibular joint disorders, mucosa alterations and symptoms of dry mouth. The aim of this study was to evaluate the salivary gland function of subjects with rheumatoid arthritis (RA comparing it to healthy controls. Subjects with other systemic conditions known to affect salivary functions were excluded. A questionnaire was applied for the evaluation of xerostomia. Resting and chewing-stimulated salivary flow rates (SFR were obtained under standard conditions. There were 145 subjects included of the study (104 RA and 38 controls. About 66.7% of the RA subjects and 2.4% in control group presented xerostomia. The median resting SFR were 0.24 ml/min for RA subjects and 0.40 mL/min for controls (p = 0.04. The median stimulated SFR were 1.31 mL/min for RA subjects and 1.52 ml/min for controls (p = 0.33. No significant differences were found between resting and stimulated SFR of RA subjects not using xerogenic medications and controls. There was significantly higher number of subjects presenting hyposalivation in the RA group than among controls, even when subjects using xerogenic medications were eliminated from the analysis. In conclusion, hyposalivation and xerostomia were more frequent among RA subjects not using xerogenic medication than among controls, although there were no significant differences in the median SFR between groups.

  4. 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

  5. Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery.

    Science.gov (United States)

    Xu, Leyuan; Cooper, Remy C; Wang, Juan; Yeudall, W Andrew; Yang, Hu

    2017-08-14

    We developed novel dendrimer hydrogels (DH)s on the basis of bioorthogonal chemistry, in which polyamidoamine (PAMAM) dendrimer generation 4.0 (G4) functionalized with strained alkyne dibenzocyclooctyne (DBCO) via PEG spacer (Mn = 2,000 g/mol) underwent strain-promoted azide-alkyne cycloaddition (SPAAC) with polyethylene glycol bisazide (PEG-BA) (Mn= 20,000 g/mol) to generate a dendrimer-PEG cross-linked network. This platform offers a high degree of functionality and modularity. A wide range of structural parameters including dendrimer generation, degree of PEGylation, loading density of clickable DBCO groups, PEG-BA chain length as well as the ratio of clickable dendrimer to PEG-BA and their concentrations can be readily manipulated to tune chemical and physical properties of DHs. We used this platform to prepare an injectable liquid DH. This bioorthogonal DH exhibited high cytocompatibility and enabled sustained release of the anticancer drug 5-fluorouracil (5-FU). Following intratumoral injection, the DH/5-FU formulation significantly suppressed tumor growth and improved survival of HN12 tumor-bearing mice by promoting tumor cell death as well as by reducing tumor cell proliferation and angiogenesis.

  6. Preliminary survey of local bacteriophages with lytic activity against multi-drug resistant bacteria.

    Science.gov (United States)

    Latz, Simone; Wahida, Adam; Arif, Assuda; Häfner, Helga; Hoß, Mareike; Ritter, Klaus; Horz, Hans-Peter

    2016-10-01

    Bacteriophages (phages) represent a potential alternative for combating multi-drug resistant bacteria. Because of their narrow host range and the ever emergence of novel pathogen variants the continued search for phages is a prerequisite for optimal treatment of bacterial infections. Here we performed an ad hoc survey in the surroundings of a University hospital for the presence of phages with therapeutic potential. To this end, 16 aquatic samples of different origins and locations were tested simultaneously for the presence of phages with lytic activity against five current, but distinct strains each from the ESKAPE-group (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae). Phages could be isolated for 70% of strains, covering all bacterial species except S. aureus. Apart from samples from two lakes, freshwater samples were largely devoid of phages. By contrast, one liter of hospital effluent collected at a single time point already contained phages active against two-thirds of tested strains. In conclusion, phages with lytic activity against nosocomial pathogens are unevenly distributed across environments with the prime source being the immediate hospital vicinity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Evaluation of Drug Administrations via Enteral Tube of Intensive Care Nurses

    OpenAIRE

    sevim celik

    2014-01-01

    Aim: The aim of this study was to analyze drug administrations via enteral tube of nurses working intensive care unit Material and Method: Cross-sectional descriptive study was realized with 91 intensive care nurses between 19 March and 9 April, 2012. Data were collected by a survey form. Data were evaluated by number, mean, standart deviation, percentages, chi-square and Fisher's exact tests. Results: Before drug administration via enteral tube, it was determined that 70.3% of nurses ...

  8. Use of internet search logs to evaluate potential drug adverse events.

    Science.gov (United States)

    Sarntivijai, S; Abernethy, D R

    2014-08-01

    Internet search logs provide an abundant source of data that can be explored for purposes such as identifying drug exposure-adverse event relationships. The methodology to rigorously conduct such evaluations is not well characterized, and the utility of such analyses is not well defined. In this issue, White and colleagues propose an approach using Internet search logs for this purpose and compare it to parallel analyses conducted using the US Food and Drug Administration's spontaneous reporting database.

  9. Evaluation of Potential Pharmacokinetic Drug-Drug Interaction between Armodafinil and Aripiprazole in Healthy Adults.

    Science.gov (United States)

    Darwish, M; Bond, M; Yang, R; Hellriegel, E T; Robertson, P

    2015-07-01

    Armodafinil, a moderate inducer of cytochrome P450 (CYP) 3A4, has been studied as adjunctive therapy to maintenance medications for major depressive episodes associated with bipolar I disorder. We evaluated the effect of daily dosing with armodafinil on the pharmacokinetics and safety of the CYP3A4 substrate aripiprazole, an atypical antipsychotic used to treat bipolar I disorder. Healthy adults received 15 mg aripiprazole alone and after armodafinil (250 mg/day) pretreatment. Pharmacokinetic parameters were derived from plasma concentrations of aripiprazole and its active metabolite, dehydro-aripiprazole, obtained over 16 days after each aripiprazole administration. Steady-state pharmacokinetics of armodafinil and its 2 circulating metabolites was assessed. Of 36 subjects enrolled, 24 were evaluable for pharmacokinetic analysis. Armodafinil reduced systemic exposure to aripiprazole (Cmax, - 8%; AUC0-∞, -34%) and dehydro-aripiprazole, which is both formed and eliminated in part via CYP3A4 (Cmax, - 10%; AUC0-∞, - 32%). Adverse events were generally consistent with known safety profiles of each agent. Systemic exposure to aripiprazole and dehydro-aripiprazole was moderately reduced following armodafinil pretreatment. The combination was generally well tolerated under the conditions studied. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Evaluation of patch test in identification of causative agent in drug rashes due to antiepileptics

    Directory of Open Access Journals (Sweden)

    Vatve Maneesha

    2000-01-01

    Full Text Available Patch test was evaluated for the identification of causative agent in cutaneous eruptions due to antiepileptics. Patch tests were carried out in twenty patients and ten controls with carbamazepine, phenytoin sodium, phenobarbitone and sodium valproate. Sodium valproate was found tobe irritant in 1 and 5% concentration and further dilution is recommended for patch testing. Patch test was positive in 14 (70% patients and in 7 with suspected drug alone, and remaining 7 were positive with more than one antiepileptic drug. We recommended patch test for identification of causative drug in rashes due to antiepileptics.

  11. Assessment of methodological quality of economic evaluations in belgian drug reimbursement applications.

    Science.gov (United States)

    Simoens, Steven

    2013-01-01

    This paper aims to assess the methodological quality of economic evaluations included in Belgian reimbursement applications for Class 1 drugs. For 19 reimbursement applications submitted during 2011 and Spring 2012, a descriptive analysis assessed the methodological quality of the economic evaluation, evaluated the assessment of that economic evaluation by the Drug Reimbursement Committee and the response to that assessment by the company. Compliance with methodological guidelines issued by the Belgian Healthcare Knowledge Centre was assessed using a detailed checklist of 23 methodological items. The rate of compliance was calculated based on the number of economic evaluations for which the item was applicable. Economic evaluations tended to comply with guidelines regarding perspective, target population, subgroup analyses, comparator, use of comparative clinical data and final outcome measures, calculation of costs, incremental analysis, discounting and time horizon. However, more attention needs to be paid to the description of limitations of indirect comparisons, the choice of an appropriate analytic technique, the expression of unit costs in values for the current year, the estimation and valuation of outcomes, the presentation of results of sensitivity analyses, and testing the face validity of model inputs and outputs. Also, a large variation was observed in the scope and depth of the quality assessment by the Drug Reimbursement Committee. Although general guidelines exist, pharmaceutical companies and the Drug Reimbursement Committee would benefit from the existence of a more detailed checklist of methodological items that need to be reported in an economic evaluation.

  12. 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.

  13. Evaluation of the resistance of a geopolymer-based drug delivery system to tampering.

    Science.gov (United States)

    Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

    2014-04-25

    Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Floating ability and drug release evaluation of gastroretentive microparticles system containing metronidazole obtained by spray drying

    Directory of Open Access Journals (Sweden)

    Laís Nohemann

    2017-04-01

    Full Text Available Abstract Gastroretentive floating microparticles were developed and evaluated for the controlled metronidazole delivery for treatment of gastric disease. Floating microparticles, varying in proportions of chitosan and hydroxypropyl methylcellulose or ethylcellulose, were obtained by spray drying. Floating microparticles were characterized by physicochemical and in vitro studies, according to their floating ability and drug delivery. Microparticles presented mean diameter from 1.05 to 2.20 µm. The infrared spectroscopy confirmed the drug encapsulation and showed no chemical linkage between microparticles components. X-ray diffraction showed changes in the drug`s solid state, from crystalline to amorphous, indicating partial drug encapsulation, due to the presence of some crystalline peaks of metronidazole in microparticles. All microparticles floated immediately in contact of simulated gastric fluid and both floating and drug release profiles were dependent of microparticles composition. Microparticles samples constituted by chitosan and hydroxypropyl methylcellulose revealed the best relationship between floating duration and drug release, remaining floating during the occurrence of the drug release, ideal condition for the floating gastroretentive systems.

  15. 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.

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

    Science.gov (United States)

    Rezaei, Sadegh; Choobbasti, Asskar Janalizadeh

    2017-12-01

    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.

  17. The US Food and Drug Administration's Risk Evaluation and Mitigation Strategy (REMS) Program - Current Status and Future Direction

    National Research Council Canada - National Science Library

    Jasmanda Wu; Juhaeri Juhaeri

    2016-01-01

      The US Food and Drug Administration (FDA) Amendments Act of 2007 granted the FDA new authorities to enhance drug safety by requiring application holders to submit a proposed Risk Evaluation and Mitigation Strategy (REMS...

  18. Drug binding to the acetylcholine receptor: Nitroxide analogs of phencyclidine and a local anesthetic

    Energy Technology Data Exchange (ETDEWEB)

    Palma, A.L.

    1988-01-01

    The interaction of noncompetitive inhibitors (NCIs) with Torpedo californica native nicotinic acetylcholine receptor (nAChR) membranes was examined primarily by the technique of electron paramagnetic resonance (EPR) spectroscopy. The goal of this work being to define some of the physical characteristics for the site(s) of association between an NCI and the nAChR membrane. A nitroxide labeled analog of a quaternary amine local anesthetic, 2-(N,N-dimethyl-N-4-(2,2,6,6-tetramethylpiperidinoxyl)amino)-ethyl 4-hexyloxybenzoate iodide (C6SLMeI), displays a strongly immobilized EPR component when added to nAChR membranes in the presence of carbamylcholine (carb). To further this work, a nitroxide labeled analog of phencyclidine (PCP), a potent NCI, was synthesized. 4-phenyl-4-(1-piperidinyl)-2,2,6,6-tetramethylpiperidinoxyl (PPT) exhibited one-third the potency of PCP in inhibiting nAChR mediated ion flux, and from competition binding studies with ({sup 3}H)PCP displayed a K{sub D} of 0.21 {mu}M towards a carb desensitized nAChR and a K{sub 0.5} of 18 {mu}M for a resting {alpha}-bungarotoxin treated nAChR.

  19. 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

  20. Design, development, and evaluation of visual aids for communicating prescription drug instructions to nonliterate patients in rural Cameroon.

    Science.gov (United States)

    Ngoh, L N; Shepherd, M D

    1997-03-01

    In this study, culturally sensitive visual aids designed to help convey drug information to nonliterate female adults who had a prescription for a solid oral dosage form of antibiotic medications were developed and evaluated. The researchers conceptualized the educational messages while a local artist produced the visual aids. Seventy-eight female ambulatory patients were evaluated for comprehension and compliance with antibiotic prescription instructions. The study was conducted in three health centers in Cameroon, West Africa and followed a pre-test, post-test, and follow-up format for three groups: two experimental, and one control. All participants were randomly assigned to either experimental or control groups, 26 patients to each group. Subjects in the experimental groups received visual aids alone or visual aids plus an Advanced Organizer. A comparison of the three groups showed that subjects in the experimental groups scored significantly higher than the control group in both the comprehension and compliance measures.

  1. 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.

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

    Science.gov (United States)

    Fattouh, Youssef

    2017-01-01

    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. PMID:28970613

  3. 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

  4. Evaluation of Planned Educational Change at the Local Education Agency Level.

    Science.gov (United States)

    Merriman, Howard O.

    Based upon a systems analysis approach, a four-stage evaluation model called CIPP (context, input, process, product) assesses innovative programs in education. The model is both a way of viewing planned educational change and a decision making tool for the administrator within the local education agency. Development of the model includes a method…

  5. 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.

  6. Evaluation of the retail market potential for locally produced paper birch lumber in Alaska.

    Science.gov (United States)

    David L. Nicholls

    2002-01-01

    An evaluation of the retail market potential for random-width paper birch ( Betula papyrifera Marsh.) lumber in Alaska was conducted. Information from lumber manufacturers and retail managers was used to identify current barriers to customer acceptance of locally produced paper birch lumber. Major retail markets and paper birch producing regions throughout Alaska were...

  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. Sources of evaluation of nuclear and renewable energy contained in the local press

    NARCIS (Netherlands)

    van der Pligt, J.; Spears, R.; Eiser, J.R.

    1987-01-01

    Examined the sources of evaluative coverage concerning nuclear power and renewable alternatives contained in local UK daily press coverage. 10 categories of source were defined for their relevance to the nuclear debate and energy issues. Out of these, only pronuclear industries and national

  9. Taste-Masking Effect of Chlorogenic Acid (CGA) on Bitter Drugs Evaluated by Taste Sensor and Surface Plasmon Resonance on the Basis of CGA-Drug Interactions.

    Science.gov (United States)

    Shiraishi, Sayuko; Haraguchi, Tamami; Nakamura, Saki; Li, Dahong; Kojima, Honami; Yoshida, Miyako; Uchida, Takahiro

    2017-01-01

    The purpose of this study was to evaluate the taste-masking effects of chlorogenic acid (CGA) on bitter drugs using taste sensor measurements and surface plasmon resonance (SPR) analysis of CGA-drug interactions. Six different bitter drugs were used: amlodipine besylate (AMD), diphenhydramine hydrochloride (DPH), donepezil hydrochloride (DNP), rebamipide (RBM), diclofenac sodium (DCF) and etodolac (ETD). Taste sensor outputs were significantly inhibited by the addition of CGA to all drugs. The inhibition ratio of the taste sensor output decreased in the following order DPH>DNP>AMD≈DCF≈RBM≈ETD. The association rate constant (ka) for the interaction between drugs and CGA as evaluated by SPR measurement also decreased in the following order DPH>DNP>AMD>DCF≈ETD≈RBM. It was suggested that basic drugs (AMD, DNP, DPH) associate more easily with CGA than acidic drugs (DCF, RBM, ETD). The inhibition ratios (%) of the taste sensor output of bitter drugs caused by CGA and the association rate constants (ka) between the drugs and CGA were significantly correlated (rs=0.886, ptaste-masking effects of CGA are due to its direct association with the drugs. CGA may therefore be a useful taste-masking agent for basic drugs.

  10. Benchmarking human protein complexes to investigate drug-related systems and evaluate predicted protein complexes.

    Directory of Open Access Journals (Sweden)

    Min Wu

    Full Text Available Protein complexes are key entities to perform cellular functions. Human diseases are also revealed to associate with some specific human protein complexes. In fact, human protein complexes are widely used for protein function annotation, inference of human protein interactome, disease gene prediction, and so on. Therefore, it is highly desired to build an up-to-date catalogue of human complexes to support the research in these applications. Protein complexes from different databases are as expected to be highly redundant. In this paper, we designed a set of concise operations to compile these redundant human complexes and built a comprehensive catalogue called CHPC2012 (Catalogue of Human Protein Complexes. CHPC2012 achieves a higher coverage for proteins and protein complexes than those individual databases. It is also verified to be a set of complexes with high quality as its co-complex protein associations have a high overlap with protein-protein interactions (PPI in various existing PPI databases. We demonstrated two distinct applications of CHPC2012, that is, investigating the relationship between protein complexes and drug-related systems and evaluating the quality of predicted protein complexes. In particular, CHPC2012 provides more insights into drug development. For instance, proteins involved in multiple complexes (the overlapping proteins are potential drug targets; the drug-complex network is utilized to investigate multi-target drugs and drug-drug interactions; and the disease-specific complex-drug networks will provide new clues for drug repositioning. With this up-to-date reference set of human protein complexes, we believe that the CHPC2012 catalogue is able to enhance the studies for protein interactions, protein functions, human diseases, drugs, and related fields of research. CHPC2012 complexes can be downloaded from http://www1.i2r.a-star.edu.sg/xlli/CHPC2012/CHPC2012.htm.

  11. 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.

  12. 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.

  13. Preparation and Evaluation of Nano-vesicles of Brimonidine Tartrate as an Ocular Drug Delivery System.

    Science.gov (United States)

    Prabhu, P; Nitish, Kumar R; Koland, M; Harish, Nm; Vijayanarayan, K; Dhondge, G; Charyulu, Rn

    2010-10-01

    The objective of the present investigation was to design a vesicular formulation of brimonidine tartrate and evaluate its ability to reduce the dosing frequency and improve the therapeutic efficacy of the drug. Nano-vesicles of brimonidine tartrate were prepared by film hydration method. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, and ex-in vitro drug release and in vivo intraocular pressure (IOP) lowering activity. The methods employed for preparation of vesicles produced nano vesicles of acceptable shape and size. The in vitro, and ex-in vitro drug release studies showed that there was slow and prolonged release of the drug, which followed zero-order kinetics. The IOP-lowering activity of nano vesicles was determined and compared with that of pure drug solution and showed that the IOP-lowering action of nano-vesicles sustained for a longer period of time. Stability studies revealed that the vesicle formulations were stable at the temperature range of 2-8°C, with no change in shape and drug content. The results of the study indicate that it is possible to develop a safe and physiologically effective topical formulation that is also convenient for patients.

  14. 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.

  15. Biocompatibility and cytotoxic evaluation of drug-loaded biodegradable guided tissue regeneration membranes.

    Science.gov (United States)

    Thomas, Nebu G; Sanil, George P; Gopimohan, Rajmohan; Prabhakaran, Jayachandran V; Thomas, George; Panda, Amulya K

    2012-10-01

    In periodontology, Guided Tissue Regeneration (GTR) is based on the concept of providing a space for entry of cells with regenerative potential into the wound environment to initiate the regeneration of structures lost due to periodontal disease. First generation GTR membranes were primarily non-absorbable membranes like expanded polytetrafluorethylene which required a second surgery for its removal. This led researchers to explore absorbable materials like collagen and synthetic biodegradable polymers to fabricate GTR membranes. In the present study, biodegradable Polylactic acid (PLA) is used to fabricate membranes with the potential to be used for GTR therapy. Biocompatibility of the PLA membranes were evaluated in a subcutaneous guinea pig model. Antimicrobial effect of the drug-loaded PLA membranes were assessed against a drug-resistant Staphylococcus aureus bacterial isolate. The cytocompatibility of the drug-loaded membranes were evaluated using HeLa cell lines. The PLA membranes were shown to be biocompatible. The drug-loaded PLA membranes showed significant activity against the bacterial isolate. Among the drug-loaded membranes, tetracycline-loaded membrane showed minimal cellular toxicity. The results of this study indicate that biodegradable drug-releasing polylactide membranes have the potential to be used for periodontal regeneration. It has the necessary characteristics of a GTR membrane like biocompatibility, space maintaining ability, and tissue integration. Among the various antimicrobial agents loaded in the PLA membranes, tetracycline-loaded membranes exhibited minimal cellular toxicity against HeLa cells; at the same time showing significant activity against a pathogenic bacterium.

  16. 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.

  17. 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 ...

  18. Gastroretentive drug delivery systems: current developments in novel system design and evaluation.

    Science.gov (United States)

    Murphy, Caragh S; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C

    2009-10-01

    The task of achieving efficient delivery of drugs that have poor bioavailability or narrow absorption windows have plagued the pharmaceutically industry for decades. Thus, much research has been dedicated to the development of novel polymeric-based gastroretentive drug delivery technologies that may optimize the bioavailability and subsequent therapeutic efficacy of such drugs. An effective approach of achieving this is through the prolongation of the gastric residence time employing several gastroretentive drug delivery mechanisms such as the use of buoyant systems, high density systems, magnetic systems, mucoadhesive systems, swelling/expanding systems, superporous hydrogels and the inclusion of gastric motility retarding agents with biocompatible polymeric materials. It is known that variations in the gastric physiology such as, gastric pH, and motility exhibit both intra-as well as inter-subject variability demonstrating a significant impact on the gastric retention time and drug delivery behavior. Nevertheless, gastroretentive drug delivery systems have shown promising results. Therefore, in this mini-review, current research and development in this field (i.e. over the last 3-5 years), the polymeric material used for the design of gastroretentive drug delivery systems and techniques employed for the pharmaceutical evaluation of gastroretentive technologies are comprehensively revealed and discussed in an assimilatory manner.

  19. 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.

  20. Evaluation of mRNA Localization Using Double Barrel Scanning Ion Conductance Microscopy.

    Science.gov (United States)

    Nashimoto, Yuji; Takahashi, Yasufumi; Zhou, Yuanshu; Ito, Hidenori; Ida, Hiroki; Ino, Kosuke; Matsue, Tomokazu; Shiku, Hitoshi

    2016-07-26

    Information regarding spatial mRNA localization in single cells is necessary for a better understanding of cellular functions in tissues. Here, we report a method for evaluating localization of mRNA in single cells using double-barrel scanning ion conductance microscopy (SICM). Two barrels in a nanopipette were filled with aqueous and organic electrolyte solutions and used for SICM and as an electrochemical syringe, respectively. We confirmed that the organic phase barrel could be used to collect cytosol from living cells, which is a minute but sufficient amount to assess cellular status using qPCR analysis. The water phase barrel could be used for SICM to image topography with subcellular resolution, which could be used to determine positions for analyzing mRNA expression. This system was able to evaluate mRNA localization in single cells. After puncturing the cellular membrane in a minimally invasive manner, using SICM imaging as a guide, we collected a small amount cytosol from different positions within a single cell and showed that mRNA expression depends on cellular position. In this study, we show that SICM imaging can be utilized for the analysis of mRNA localization in single cells. In addition, we fully automated the pipet movement in the XYZ-directions during the puncturing processes, making it applicable as a high-throughput system for collecting cytosol and analyzing mRNA localization.

  1. Preliminary evaluation of anti-tuberculosis potential of siderophores against drug-resistant Mycobacterium tuberculosis by mycobacteria growth indicator tube-drug sensitivity test

    OpenAIRE

    Gokarn, Karuna; Pal, Ramprasad B.

    2017-01-01

    Background Alternative treatment strategies have become essential in overcoming the problem of drug-resistant Mycobacterium tuberculosis (Mtb). In this preliminary in vitro study, the anti-tuberculosis (anti-TB) activity of exogenous iron chelators (xenosiderophores) such as Exochelin-MS (Exo-MS) and Deferoxamine-B (DFO-B) was evaluated against ten multi-drug-resistant (MDR) and seven pyrazinamide-resistant (PZA R ) Mtb isolates. Methods Mycobacteria Growth Indicator Tube-Drug Susceptibility ...

  2. 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.

  3. Bioequivalence Evaluations of Generic Dry Powder Inhaler Drug Products: Similarities and Differences Between Japan, USA, and the European Union.

    Science.gov (United States)

    Kuribayashi, Ryosuke; Yamaguchi, Toru; Sako, Hanaka; Takishita, Tomoko; Takagi, Kazunori

    2017-03-01

    In Japan, the development of generic oral dry powder inhaler (DPI) drug products for marketing approval has recently increased. The Pharmaceuticals and Medical Devices Agency (PMDA) considers the required data for each drug product in the consultation meeting. However, guidelines for DPI drug products have been published by the US Food and Drug Administration and the European Medicines Agency. Recently, the basic principles of bioequivalence evaluations of generic DPI drug products were published in March 2016 by the Ministry of Health, Labour and Welfare. The document mainly outlines the current understanding regarding the bioequivalence evaluations of generic DPI drug products based on knowledge from PMDA consultation meetings. In this review, we compared the bioequivalence evaluations of DPI drug products among Japan, USA, and the European Union and discuss future development of generic DPI drug products in Japan.

  4. Evaluation of local flow conditions in jailed side branch lesions using computational fluid dynamics.

    Science.gov (United States)

    Na, Sang-Hoon; Koo, Bon-Kwon; Kim, Jeong Chul; Yang, Han-Mo; Park, Kyung-Woo; Kang, Hyun-Jae; Kim, Hyo-Soo; Oh, Byung-Hee; Park, Young-Bae

    2011-02-01

    Lesions of vascular bifurcation and their treatment outcomes have been evaluated by anatomical and physiological methods, such as intravascular ultrasound and fractional flow reserve (FFR). However, local changes in flow dynamics in lesions of bifurcation have not been well evaluated. This study aimed at evaluating changes in the local flow patterns of bifurcation lesions. Eight (n=8) representative simulation-models were constructed: 1 normal bifurcation, 5 main-branch (MB) stenting models with various side-branch (SB) stenoses (ostial or non-ostial 75% diameter stenosis with 1- or 2-cm lesion lengths, ostial 75% diameter stenosis caused by carina shift), and 2 post-kissing models (no or 50% SB residual stenosis). Pressure, velocity, and wall shear stress (WSS) profiles around the bifurcation sites were investigated using computational fluid dynamics. Post-stenting models revealed significant pressure drop in the SB (FFRkissing models, there was no significant pressure drop. All post-stenting models revealed eccentric low velocity flow patterns and areas of low WSS, primarily in the lateral wall on distal MB. Post-kissing angioplasty improved pressure drop in the SB but resulted in alteration of flow distribution in the MB. In the carina shift model, kissing ballooning resulted in deteriorated local flow conditions due to increased area of low velocity and WSS. This study suggests that the most commonly used bifurcation intervention strategy may cause local flow disturbances, which may partially explain high restenosis and event rates in patients with bifurcation lesions.

  5. The evaluation and use of economic evidence to inform cancer drug reimbursement decisions in Canada.

    Science.gov (United States)

    Yong, Jean H E; Beca, Jaclyn; Hoch, Jeffrey S

    2013-03-01

    Cost-effectiveness evidence is increasingly considered in the reimbursement decisions of pharmaceuticals. In some jurisdictions such as the UK and Canada, pharmaceutical manufacturers are required to submit economic evaluations when seeking reimbursement. Our objectives were to describe the role of economic evidence in the cancer drug review process in Canada, and to investigate the nature of problems encountered in the review and interpretation of economic evidence used in the process. We conducted a retrospective review of cancer drug review meeting minutes and reviewers' comments on pharmacoeconomic studies submitted to the oncology drug review process in Canada. We used pharmacoeconomic reviewers' reports and relevant cancer drug review expert advisory committee meeting minutes during the first year of the review process (April 2007 to March 2008). Fifteen economic submissions were reviewed. One-third of the studies had flaws significant enough that the advisory committee could not determine the cost effectiveness of the drugs from the results. The common issues outlined by the reviewers and committee were related to the uncertainty of comparative clinical benefits, quality of life and costs. The reviewers felt that few analyses provided sufficient sensitivity analyses around key variables to assess the robustness of results. Most problems identified by reviewers are simple to fix and do not involve advanced methods. Canada has a separate review process for making cancer drug funding recommendations, and this process uses both clinical and economic evidence. The committee could not determine the value for money of the drugs from several of the submitted pharmacoeconomic analyses. Transparent analyses and detailed critique of evidence are crucial to the use of economic evidence in reimbursement decisions. Rigorous evaluation is resource intensive and may benefit from a shared drug review process among several jurisdictions.

  6. Fishing Anti-Inflammatories from Known Drugs: In Silico Repurposing, Design, Synthesis and Biological Evaluation of Bisacodyl Analogues.

    Science.gov (United States)

    Veitía, Maité Sylla-Iyarreta; Mota, Dany Siverio; Lerari, Vanessa; Marín, Marta; Giner, Rosa M; Muro, Liliana Vicet; Guerra, Yankier Rivero; Dumas, Françoise; Ferroud, Clotilde; de Witte, Peter A M; Crawford, Alexander D; Arán, Vicente J; Ponce, Yovani Marrero

    2017-08-17

    Herein is described in silico repositioning, design, synthesis, biological evaluation and structure-activity relationship (SAR) of an original class of anti-inflammatory agents based on a polyaromatic pharmacophore structurally related to bisacodyl (BSL) drug used in therapeutic as laxative. We describe the potential of TOMOCOMD-CARDD methods to find out new anti-inflammatory drug-like agents from a diverse series of compounds using the total and local atom based bilinear indices as molecular descriptors. The models obtained were validated by biological studies, identifying BSL as the first anti-inflammatory lead-like using in silico repurposing from commercially available drugs. Several biological in vitro and in vivo assays were performed in order to understand its mechanism of action. A set of analogues of BSL was prepared using low-cost synthetic procedures and further biologically investigated in zebrafish models. Compound 5c and 7e exhibited the best antiinflammatory activities and represent new promising anti-inflammatory agents for further preclinical development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Evaluating the abuse potential of psychedelic drugs for medical use in humans.

    Science.gov (United States)

    Heal, David J; Gosden, Jane; Smith, Sharon L

    2018-02-07

    Psychedelics comprise drugs come from various pharmacological classes including 5-HT 2A agonists, indirect 5-HT agonists, e.g. MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e. no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i.e. schedules 2-5. Although abuse of the psychedelics is well documented, a systematic preclinical and clinical evaluation of the risks they pose in a medical-use setting does not exist. We describe the non-clinical tests required for a regulatory evaluation of abuse/dependence risks, i.e. drug-discrimination, intravenous self-administration and physical dependence liability. A synopsis of the existing data for the various types of psychedelics is provided and we describe our findings with psychedelic drugs in these models. FDA recently issued its guidance on abuse/dependence evaluation of drug-candidates [59]. We critically review the guidance, discuss the impact this document will have on non-clinical abuse/dependence testing, and offer advice on how non-clinical abuse/dependence experiments can be designed to meet not only the expectations of FDA, but also other regulatory agencies. Finally, we offer views on how these non-clinical tests can be refined to provide more meaningful information to aid the assessment of the risks posed by CNS drug-candidates for abuse and physical dependence. Copyright © 2018. Published by Elsevier Ltd.

  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. Studies in Multifunctional Drug Development: Preparation and Evaluation of 11beta-Substituted Estradiol-Drug Conjugates, Cell Membrane Targeting Imaging Agents, and Target Multifunctional Nanoparticles

    Science.gov (United States)

    Dao, KinhLuan Lenny D.

    with the PSMA-targeted mfAuNPs demonstrated significant selective uptake and localization properties in LnCaP and PC-3 prostate cancer cells.4 References: (1) Dao, K.-L.; Hanson, R. N.: Targeting the Estrogen Receptor using Steroid-Therapeutic Drug Conjugates (Hybrids). Bioconjugate Chemistry 2012. DOI: 10.1021/bc300378e. (2) Dao, K.-L.; Sawant, R. R.; Hendricks, J. A.; Ronga, V.; Torchilin, V. P.; Hanson, R. N.: Design, Synthesis, and Initial Biological Evaluation of a Steroidal Anti-Estrogen-Doxorubicin Bioconjugate for Targeting Estrogen Receptor-Positive Breast Cancer Cells. Bioconjugate Chemistry 2012, 23, 785-795. (3) Design, Synthesis, and in vivo PET imaging of radioligand 18F-11beta-substituted estradiol (18F-11betaAE) in breast cancer (manuscript in prep.) (4) Prostate Cancer-Specific Drug Delivery and Imaging Systems: Design, Synthesis, and Biological Evaluation of Multi-functional Gold Nanoparticles (manuscript in prep.)

  10. 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

    2018-01-16

    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.

  11. Quantitative evaluation of learning and memory trace in studies of mnemotropic effects of immunotropic drugs.

    Science.gov (United States)

    Kiseleva, N M; Novoseletskaya, A V; Voevodina, Ye B; Kozlov, I G; Inozemtsev, A N

    2012-12-01

    Apart from restoration of disordered immunological parameters, tactivin and derinat exhibit a pronounced effect on the higher integrative functions of the brain. Experiments on Wistar rats have shown that these drugs accelerated conditioning of food and defense responses. New methods for quantitative evaluation of memory trace consolidation are proposed.

  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. Subjective Evaluation of the Microenvironment Generated by a Hospital Bed with Localized Ventilation System

    DEFF Research Database (Denmark)

    Kehayova, Nushka; Bolashikov, Zhecho Dimitrov; Melikov, Arsen Krikor

    2016-01-01

    A novel method for local hospital bed ventilation, called HBIVCU (Hospital Bed with Integrated Ventilation and Cleansing Unit), was studied in a human subject experiment. The goal of this study was to identify human response to the microenvironment generated by a hospital bed with installed HBIVCU...... and to compare with human response to the micro-environment at a hospital bed without local ventilation. 32 participants took part in two experimental conditions - hospital bed with and without installed HBIVCU. Subject’s votes on the bed microenvironment were collected via standardized questionnaires....... The subjects evaluated the perceived air quality in the ventilated bed as better compared to that in the non-ventilated bed. The whole body thermal sensation (WTS) and acceptability votes were decreasing over time for the non-ventilated bed condition. Significant differences in the local thermal sensation LTS...

  14. Intra-articular drug delivery from an optimized topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment: does the topical patch really enhance a local treatment?

    Science.gov (United States)

    Xi, Honglei; Cun, Dongmei; Xiang, Rongwu; Guan, Yanli; Zhang, Yuxiu; Li, Yuanru; Fang, Liang

    2013-07-10

    Patients with rheumatoid arthritis (RA) often bear joint destruction and symptomatic pain. The aim of this work is to develop a compound transdermal patch containing teriflunomide (TEF) and lornoxicam (LOX) to transport these drugs across the skin with the isochronous permeation rates for RA therapy and investigate intra-articular delivery of TEF and LOX following transdermal patches applied topically. The salts of TEF and LOX with organic amines diethylamine (DEtA), triethylamine (TEtA), diethanolamine (DEA), triethanolamine (TEA) and N-(2'-hydroxy-ethanol)-piperdine (NP) were prepared to improve the skin permeation of the parent drug. The optimized patch formulation is obtained from a 3-factor, 2-level central composite design. After topical application of the optimized compound patch to only one knee joint in rabbit, intra-articular delivery of TEF and LOX on the application site was compared with that on the non-application site. Anti-inflammatory and analgesic effects of the optimized compound patch were evaluated using the adjuvant arthritis model and the pain model induced by acetic acid, respectively. The in vitro experiment results showed that the amine salts of TEF and LOX, especially TEF-TEtA and LOX-TEtA, enhanced the skin permeation of TEF and LOX from the transdermal patch system. The optimal formulation successfully displayed isochronous permeation rates for TEF and LOX across rabbit skin, and was defined with 5% of TEF-TEtA, 10% of LOX-TEtA and 15% of azone. The in vivo study showed that TEF and LOX from transdermal patches were transferred into skin, ligament and fat pad on the application site by direct diffusion and on the non-application site by the redistribution of systemic blood supply, while local absorption of TEF and LOX in synovial fluid originated from the systemic blood supply rather than direct diffusion. In the RA rat model, the results of swelling inhibition on primary arthritis of bilateral hind paws further confirmed the above

  15. Evaluation of Herb-Drug Interactions of Hovenia dulcis Fruit Extracts.

    Science.gov (United States)

    Park, Jong Suk; Rehman, Shaheed Ur; Kim, In Sook; Choi, Min Sun; Na, Chun-Soo; Yoo, Hye Hyun

    2017-01-01

    Hovenia dulcis (Rhamnaceae) fruits are popularly used as herbal medicines or dietary supplements in Asian countries due to functions such as liver protection and detoxification from alcohol poisoning. Accordingly, it is very likely for dietary supplemental products, including H. dulcis fruit extracts, to be taken with prescription drugs. In this study, possible food-drug interactions involving H. dulcis fruit extracts were evaluated based on the inhibition of cytochrome P450 (CYP) enzyme activity. The water extract of H. dulcis fruit extracts was incubated in human liver microsomes with CYP-specific substrates. The formation of the CYP-specific metabolites was measured using liquid chromatography-tandem mass spectrometry. H. dulcis fruit extracts showed negligible effects on seven CYP isozyme activities at all concentrations tested. This result suggests that H. dulcis fruit extracts may have minimal pharmacokinetic interactions with coadministered drugs through the modulation of CYP enzymes. Food-drug interactions involving H. dulcis fruit extracts were evaluated.The inhibition of CYPs by H. dulcis extracts was tested.H. dulcis extracts showed negligible effects on CYP activities.H. dulcis extracts may have minimal pharmacokinetic interactions with co-administered drugs. Abbreviations Used: CYP: cytochrome P450 enzymes, HPLC: High performance liquid chromatography, LC-MS/MS : liquid chromatography-tandem mass spectrometry, MRM: multiple-reaction monitoring.

  16. In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery.

    Science.gov (United States)

    Rahimi, Maham; Wadajkar, Aniket; Subramanian, Khaushik; Yousef, Monet; Cui, Weina; Hsieh, Jer-Tsong; Nguyen, Kytai Truong

    2010-10-01

    Previously uncharacterized poly(N-isopropylacrylamide-acrylamide-allylamine)-coated magnetic nanoparticles (MNPs) were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Properties of these nanoparticles such as size, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. Spherical core-shell nanoparticles with a diameter of 100 nm showed significantly lower systemic toxicity than did bare MNPs, as well as doxorubicin encapsulation efficiency of 72%, and significantly higher doxorubicin release at 41°C compared with 37°C, demonstrating their temperature sensitivity. Released drugs were also active in destroying prostate cancer cells (JHU31). Furthermore, the nanoparticle uptake by JHU31 cells was dependent on dose and incubation time, reaching saturation at 500 μg/mL and 4 hours, respectively. In addition, magnetic resonance imaging capabilities of the particles were observed using agarose platforms containing cells incubated with nanoparticles. Future work includes investigation of targeting capability and effectiveness of these nanoparticles in vivo using animal models. In this paper, previously uncharacterized magnetic nanoparticles were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Various properties of these nanoparticles were evaluated in vitro for targeted drug delivery. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Evaluation of drug-excipient interaction in the formulation of celecoxib tablets.

    Science.gov (United States)

    Bozdağ-Pehlivan, Sibel; Subaşi, Birsel; Vural, Imran; Unlü, Nurşen; Capan, Yilmaz

    2011-01-01

    In the present study, the possible interactions between celecoxib and some excipients (colloidal silicon dioxide (Aerosil), microcrystalline cellulose (Avicel PH 102), lactose anhydrous, magnesium stearate, cross-povidone and talc) were evaluated by examining the pure drug or drug-excipient powder mixtures which were stored under different conditions (25 +/- 2 degrees C, 60% RH +/- 5% RH or 40 + 2 degrees C, 75% RH +/- 5% RH) and different period (30 or 60 days) using DSC, FT-IR and HPLC. In order to investigate the possibility of celecoxib-excipient interaction in aqueous medium, dispersions of the pure drug or drug in physical powder mixture (1:1 w/w) in water (1%, w/v) were also prepared and evaluated by FT-IR and HPLC at day 0 and day 7 (40 +/- 2 degrees C). The interaction between celecoxib and magnesium stearate or colloidal silicon dioxide were determined in the aqueous dispersions by FT-IR. Different tablet formulations with or without excipients tested were prepared, and assessed for drug dissolution and permeability.

  18. 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.

  19. Coping with problematic drug use in the family: An evaluation of the Stepping Stones program.

    Science.gov (United States)

    Gethin, Anni; Trimingham, Tony; Chang, Theo; Farrell, Michael; Ross, Joanne

    2016-07-01

    Problematic substance use by an individual is often highly destructive to their family, creating emotional turmoil and destroying healthy family functioning. The aim of this study was to evaluate the impact of participation in the Stepping Stones family support program on the coping capacity of family members affected by another's substance use. A pre and post study of the Stepping Stones intervention for families was conducted, involving 108 participants recruited from March 2013 to March 2014. Significant improvement in coping across all domains was observed post course and at follow up on both outcome measures (Coping Questionnaire and the Family Drug Support Questionnaire). Improvements for participants were either increased or sustained at 3 months follow up. Participants recorded high satisfaction ratings. The findings from this study demonstrate that participation in the Stepping Stones program assists family members to cope better with problematic substance use of a family member, as indicated by reductions in negative coping strategies, such as over-engagement, making excuses for the drug user or hopelessly tolerating the problem, and improvements in positive coping strategies such as self-care and engagement with their own activities and interests. [Gethin A, Trimingham T, Chang T, Farrell M, Ross J. Coping with problematic drug use in the family: An evaluation of the Stepping Stones program. Drug Alcohol Rev 2016;35:470-476]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

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

    Science.gov (United States)

    Pentak, Danuta

    2016-05-01

    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).

  1. Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    Gisele Alborghetti Nai

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0 mg/kg; group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p 0.05. CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated.

  2. 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.

  3. Evaluation of Speech Intelligibility and Sound Localization Abilities with Hearing Aids Using Binaural Wireless Technology.

    Science.gov (United States)

    Ibrahim, Iman; Parsa, Vijay; Macpherson, Ewan; Cheesman, Margaret

    2013-01-02

    Wireless synchronization of the digital signal processing (DSP) features between two hearing aids in a bilateral hearing aid fitting is a fairly new technology. This technology is expected to preserve the differences in time and intensity between the two ears by co-ordinating the bilateral DSP features such as multichannel compression, noise reduction, and adaptive directionality. The purpose of this study was to evaluate the benefits of wireless communication as implemented in two commercially available hearing aids. More specifically, this study measured speech intelligibility and sound localization abilities of normal hearing and hearing impaired listeners using bilateral hearing aids with wireless synchronization of multichannel Wide Dynamic Range Compression (WDRC). Twenty subjects participated; 8 had normal hearing and 12 had bilaterally symmetrical sensorineural hearing loss. Each individual completed the Hearing in Noise Test (HINT) and a sound localization test with two types of stimuli. No specific benefit from wireless WDRC synchronization was observed for the HINT; however, hearing impaired listeners had better localization with the wireless synchronization. Binaural wireless technology in hearing aids may improve localization abilities although the possible effect appears to be small at the initial fitting. With adaptation, the hearing aids with synchronized signal processing may lead to an improvement in localization and speech intelligibility. Further research is required to demonstrate the effect of adaptation to the hearing aids with synchronized signal processing on different aspects of auditory performance.

  4. Evaluation of speech intelligibility and sound localization abilities with hearing aids using binaural wireless technology

    Directory of Open Access Journals (Sweden)

    Iman Ibrahim

    2012-12-01

    Full Text Available Wireless synchronization of the digital signal processing (DSP features between two hearing aids in a bilateral hearing aid fitting is a fairly new technology. This technology is expected to preserve the differences in time and intensity between the two ears by co-ordinating the bilateral DSP features such as multichannel compression, noise reduction, and adaptive directionality. The purpose of this study was to evaluate the benefits of wireless communication as implemented in two commercially available hearing aids. More specifically, this study measured speech intelligibility and sound localization abilities of normal hearing and hearing impaired listeners using bilateral hearing aids with wireless synchronization of multichannel Wide Dynamic Range Compression (WDRC. Twenty subjects participated; 8 had normal hearing and 12 had bilaterally symmetrical sensorineural hearing loss. Each individual completed the Hearing in Noise Test (HINT and a sound localization test with two types of stimuli. No specific benefit from wireless WDRC synchronization was observed for the HINT; however, hearing impaired listeners had better localization with the wireless synchronization. Binaural wireless technology in hearing aids may improve localization abilities although the possible effect appears to be small at the initial fitting. With adaptation, the hearing aids with synchronized signal processing may lead to an improvement in localization and speech intelligibility. Further research is required to demonstrate the effect of adaptation to the hearing aids with synchronized signal processing on different aspects of auditory performance.

  5. Evaluation of speech intelligibility and sound localization abilities with hearing aids using binaural wireless technology

    Directory of Open Access Journals (Sweden)

    Iman Ibrahim

    2013-01-01

    Full Text Available Wireless synchronization of the digital signal processing (DSP features between two hearing aids in a bilateral hearing aid fitting is a fairly new technology. This technology is expected to preserve the differences in time and intensity between the two ears by co-ordinating the bilateral DSP features such as multichannel compression, noise reduction, and adaptive directionality. The purpose of this study was to evaluate the benefits of wireless communication as implemented in two commercially available hearing aids. More specifically, this study measured speech intelligibility and sound localization abilities of normal hearing and hearing impaired listeners using bilateral hearing aids with wireless synchronization of multichannel Wide Dynamic Range Compression (WDRC. Twenty subjects participated; 8 had normal hearing and 12 had bilaterally symmetrical sensorineural hearing loss. Each individual completed the Hearing in Noise Test (HINT and a sound localization test with two types of stimuli. No specific benefit from wireless WDRC synchronization was observed for the HINT; however, hearing impaired listeners had better localization with the wireless synchronization. Binaural wireless technology in hearing aids may improve localization abilities although the possible effect appears to be small at the initial fitting. With adaptation, the hearing aids with synchronized signal processing may lead to an improvement in localization and speech intelligibility. Further research is required to demonstrate the effect of adaptation to the hearing aids with synchronized signal processing on different aspects of auditory performance.

  6. Internationalization and localization: evaluating and testing a Website for Asian users.

    Science.gov (United States)

    Rau, Pei-Luen Patrick; Liang, Sheau-Farn Max

    2003-01-15

    The objective of this study was to combine internationalization and localization of Websites and improvement of Website usability with user-centred design methods. This study designed for internationalization and localization of Websites for Asian users, and implemented usability engineering into every phase of Website usability testing, based on the internationalization and localization perspectives of the honeywell.com/your home Website. The first step was to develop the usage scenarios. Three Asian usability specialists carried out one heuristic evaluation session for the current honeywell.com/your home Website. The usability problems were analysed and possible solutions to these problems were discussed. In the next phase, cluster analysis was utilized to test current information architecture. The results provided options for future information architecture development for this Website. Finally, a performance measurement test was conducted to investigate the performance for Asian users. Based on the results, suggestions for improving the Website usability from the localization perspective were provided. The results demonstrate the user-centred design (UCD) approach and stress international and local issues in Website development to Website designers.

  7. Successful treatment of osseous lesion associated with palatoradicular groove using local drug delivery and guided tissue regeneration: A report of two cases

    Directory of Open Access Journals (Sweden)

    Jayaprakash S Gadagi

    2012-01-01

    Full Text Available Developmental grooves are not rare and often appear on maxillary lateral and central incisors and are an important predisposing factor to localized periodontal disease. Various techniques have been adopted to eliminate the groove and regenerate lost periodontium. This report of two cases describes the technique of using the local drug delivery system with chlorehexidine and the guided tissue regeneration (GTR to control the disease progression and regeneration.

  8. 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

    2017-10-06

    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.

  9. Evaluation of angiotensin II receptor blockers for drug formulary using objective scoring analytical tool

    Directory of Open Access Journals (Sweden)

    Lim TM

    2012-09-01

    Full Text Available Drug selection methods with scores have been developed and used worldwide for formulary purposes. These tools focus on the way in which the products are differentiated from each other within the same therapeutic class. Scoring Analytical Tool (SAT is designed based on the same principle with score and is able to assist formulary committee members in evaluating drugs either to add or delete in a more structured, consistent and reproducible manner. Objective: To develop an objective SAT to facilitate evaluation of drug selection for formulary listing purposes. Methods: A cross-sectional survey was carried out. The proposed SAT was developed to evaluate the drugs according to pre-set criteria and sub-criteria that were matched to the diseases concerned and scores were then assigned based on their relative importance. The main criteria under consideration were safety, quality, cost and efficacy. All these were converted to questionnaires format. Data and information were collected through self-administered questionnaires that were distributed to medical doctors and specialists from the established public hospitals. A convenient sample of 167 doctors (specialists and non-specialists were taken from various disciplines in the outpatient clinics such as Medical, Nephrology and Cardiology units who prescribed ARBs hypertensive drugs to patients. They were given a duration of 4 weeks to answer the questionnaires at their convenience. One way ANOVA, Kruskal Wallis and post hoc comparison tests were carried out at alpha level 0.05. Results: Statistical analysis showed that the descending order of ARBs preference was Telmisartan or Irbesartan or Losartan, Valsartan or Candesartan, Olmesartan and lastly Eprosartan. The most cost saving ARBs for hypertension in public hospitals was Irbesartan. Conclusion: SAT is a tool which can be used to reduce the number of drugs and retained the most therapeutically appropriate drugs in the formulary, to determine most

  10. Evaluation of Some Local Egyptian Plants as a Source of Chlorophyll Pigments

    OpenAIRE

    Hammouda, F. M. [فايزة محمود حمودة; Ismail, S. I.; Hussiney, H. A.; Hussein, A. A.

    1994-01-01

    Four plant materials viz. Spinacia oleracae Linn, (spinach), Beta vulgaris Limm (chard), Medicago sativa Linn, (alfalfa) and Petroselinum sativum Hoff. (parsely) were studied as local sources for the preparation of chlorophyll pigments as natural green colour additives. Processing of the plant materials were carried out under different conditions viz. blanching, non-blanching followed by drying in air or electrical oven or in solar dehydrating oven. The qualitative and quantitative evaluation...

  11. Strategic Performance Management Evaluation for the Navy’s Splice Local Area Networks.

    Science.gov (United States)

    1985-04-01

    result in a high degree of achievement of objectives.#’ [ef. 7: p.4] The process described by Henry Fayol is as follows: ": (a) visualizing possible future...FAD-Al6i 198 STRATEGIC PERFORMANCE MANAGEMENT EVALUATION FOR THE t/2 NAVY’S SPL.ICE LOCAL AREA NET&JORKS(U) NAVAL POSTGRADUATE SCHOOL MONTEREY CA D D...1963-A NAVAL POSTGRADUATE SCHOOL Monterey, California i .4 2f 91%5,! I )85 4A THESIS . STRATEGIC PERFORMANCE MANAGEMENT EVALUATION b FOR THE NAVY’S

  12. An experimental evaluation of drug-induced mutational meltdown as an antiviral treatment strategy.

    Science.gov (United States)

    Bank, Claudia; Renzette, Nicholas; Liu, Ping; Matuszewski, Sebastian; Shim, Hyunjin; Foll, Matthieu; Bolon, Daniel N A; Zeldovich, Konstantin B; Kowalik, Timothy F; Finberg, Robert W; Wang, Jennifer P; Jensen, Jeffrey D

    2016-11-01

    The rapid evolution of drug resistance remains a critical public health concern. The treatment of influenza A virus (IAV) has proven particularly challenging, due to the ability of the virus to develop resistance against current antivirals and vaccines. Here, we evaluate a novel antiviral drug therapy, favipiravir, for which the mechanism of action in IAV involves an interaction with the viral RNA-dependent RNA polymerase resulting in an effective increase in the viral mutation rate. We used an experimental evolution framework, combined with novel population genetic method development for inference from time-sampled data, to evaluate the effectiveness of favipiravir against IAV. Evaluating whole genome polymorphism data across 15 time points under multiple drug concentrations and in controls, we present the first evidence for the ability of IAV populations to effectively adapt to low concentrations of favipiravir. In contrast, under high concentrations, we observe population extinction, indicative of mutational meltdown. We discuss the observed dynamics with respect to the evolutionary forces at play and emphasize the utility of evolutionary theory to inform drug development. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  13. Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs.

    Science.gov (United States)

    Hayakawa, Yoshihiro; Kawada, Manabu; Nishikawa, Hiroyoshi; Ochiya, Takahiro; Saya, Hideyuki; Seimiya, Hiroyuki; Yao, Ryoji; Hayashi, Masahiro; Kai, Chieko; Matsuda, Akira; Naoe, Tomoki; Ohtsu, Atsushi; Okazaki, Taku; Saji, Hideo; Sata, Masataka; Sugimura, Haruhiko; Sugiyama, Yuichi; Toi, Masakazu; Irimura, Tatsuro

    2016-02-01

    Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Fusion of multichannel local and global structural cues for photo aesthetics evaluation.

    Science.gov (United States)

    Luming Zhang; Yue Gao; Zimmermann, Roger; Qi Tian; Xuelong Li

    2014-03-01

    Photo aesthetic quality evaluation is a fundamental yet under addressed task in computer vision and image processing fields. Conventional approaches are frustrated by the following two drawbacks. First, both the local and global spatial arrangements of image regions play an important role in photo aesthetics. However, existing rules, e.g., visual balance, heuristically define which spatial distribution among the salient regions of a photo is aesthetically pleasing. Second, it is difficult to adjust visual cues from multiple channels automatically in photo aesthetics assessment. To solve these problems, we propose a new photo aesthetics evaluation framework, focusing on learning the image descriptors that characterize local and global structural aesthetics from multiple visual channels. In particular, to describe the spatial structure of the image local regions, we construct graphlets small-sized connected graphs by connecting spatially adjacent atomic regions. Since spatially adjacent graphlets distribute closely in their feature space, we project them onto a manifold and subsequently propose an embedding algorithm. The embedding algorithm encodes the photo global spatial layout into graphlets. Simultaneously, the importance of graphlets from multiple visual channels are dynamically adjusted. Finally, these post-embedding graphlets are integrated for photo aesthetics evaluation using a probabilistic model. Experimental results show that: 1) the visualized graphlets explicitly capture the aesthetically arranged atomic regions; 2) the proposed approach generalizes and improves four prominent aesthetic rules; and 3) our approach significantly outperforms state-of-the-art algorithms in photo aesthetics prediction.

  15. 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.

  16. Evaluation of surgical treatment of carpal tunnel syndrome using local anesthesia

    Directory of Open Access Journals (Sweden)

    Marco Felipe Francisco Honorato Barros

    2016-02-01

    Full Text Available ABSTRACT OBJECTIVE: To evaluate the results and complications from surgical treatment of carpal tunnel syndrome by means of an open route, using a local anesthesia technique comprising use of a solution of lidocaine, epinephrine and sodium bicarbonate. MATERIAL AND METHODS: This was a cohort study conducted through evaluating the medical files of 16 patients who underwent open surgery to treat carpal tunnel syndrome, with use of local anesthesia consisting of 20 mL of 1% lidocaine, adrenaline at 1:100,000 and 2 mL of sodium bicarbonate. The DASH scores before the operation and six months after the operation were evaluated. Comparisons were made regarding the intensity of pain at the time of applying the anesthetic and during the surgical procedure, and in relation to other types of procedure. RESULTS: The DASH score improved from 65.17 to 16.53 six months after the operation (p < 0.01. In relation to the anesthesia, 75% of the patients reported that this technique was better than or the same as venous puncture and 81% reported that it was better than a dental procedure. Intraoperative pain occurred in two cases. There were no occurrences of ischemia. CONCLUSION: Use of local anesthesia for surgically treating carpal tunnel syndrome is effective for performing the procedure and for the final result.

  17. Quantitative evaluation of software packages for single-molecule localization microscopy.

    Science.gov (United States)

    Sage, Daniel; Kirshner, Hagai; Pengo, Thomas; Stuurman, Nico; Min, Junhong; Manley, Suliana; Unser, Michael

    2015-08-01

    The quality of super-resolution images obtained by single-molecule localization microscopy (SMLM) depends largely on the software used to detect and accurately localize point sources. In this work, we focus on the computational aspects of super-resolution microscopy and present a comprehensive evaluation of localization software packages. Our philosophy is to evaluate each package as a whole, thus maintaining the integrity of the software. We prepared synthetic data that represent three-dimensional structures modeled after biological components, taking excitation parameters, noise sources, point-spread functions and pixelation into account. We then asked developers to run their software on our data; most responded favorably, allowing us to present a broad picture of the methods available. We evaluated their results using quantitative and user-interpretable criteria: detection rate, accuracy, quality of image reconstruction, resolution, software usability and computational resources. These metrics reflect the various tradeoffs of SMLM software packages and help users to choose the software that fits their needs.

  18. Evaluation of Llaima volcano activities for localization and classification of LP, VT and TR events

    Science.gov (United States)

    Dehghan Firoozabadi, Ali; Seguel, Fabian; Soto, Ismael; Guevara, David; Huenupan, Fernando; Curilem, Millaray; Franco, Luis

    2017-09-01

    Evaluation of seismic signals is one of the most important research topics on Volcanology. Volcanoes have daily activity; therefore, high speed evaluation of recorded signals is a challenge for improving the study of the natural phenomena occurring inside these natural formations. The aim of this paper is the evaluation (denoising, localization and classification) and analysis of Llaima volcano activities, one of the most actives volcanoes in South America. Different already proposed methods, such as, Butterworth, Spectral Subtraction (SS) and Wiener Filter (WF) are compared to the proposed Modified Spectral Subtraction (MSS) and Modified Wiener Filter (MWF) to find the best method for denoising the volcano signals. Then, event localization based on received signals of volcano is performed. In this step, Time Delay Estimation (TDE)-based method is used on data acquired from 3 mechanical sensors located in the volcano area. The proposed method is used to estimate the area for event location. The proposed denoising methods make the starting point for the event more evident to increase the localization accuracy for events where the starting point is difficult to find. In the last step, a method based on the novel DNN technique is proposed to classify the three main events occurring in the Llaima volcano (TR (Tremor), LP (Long Period) and VT (Volcano Tectonic)).

  19. [The use of pharmacological criteria in the toxicological evaluation of veterinary drugs].

    Science.gov (United States)

    van Leeuwen, F X

    1990-09-01

    The toxicological evaluation of residues of veterinary drugs in foods of animal origin, which is done within the framework of the Netherlands Veterinary Drugs Act, is based on an EEC guide line in which, in addition to the clinical and analytical criteria, the requirements regarding the pharmacological and toxicological evaluation are laid down. In principle, this evaluation is based on classical toxicological criteria. As veterinary drugs have a specific pharmacological action, it is essential that these pharmacological effects should be in included in the toxicological evaluation in view of an adequate protection of public health. The selected starting point is that a pharmacological effect desired in a target animal is regarded as an undesirable effect in consumers. In this presentation, two examples are referred to, viz. the bèta agonist clenbuterol and the bèta-blocking agent carazolol; the approach is compared with a 'classical' toxicological evaluation. This shows that the acceptable daily intake in human individuals (ADI), based on pharmacological criteria is lower by a factor of approximately 50 than is the ADI on the basis of 'classical' toxicological criteria. This clearly illustrates the value of this approach in protecting the health of consumers.

  20. Local co-administration of gene-silencing RNA and drugs in cancer therapy: State-of-the art and therapeutic potential.

    Science.gov (United States)

    Larsson, Mikael; Huang, Wei-Ting; Liu, Dean-Mo; Losic, Dusan

    2017-04-01

    Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery. The combination of gene-silencing RNA with drugs in nanocarriers for localized delivery is emerging with promising results. In this review, the current progress and strategies for local co-administration of RNA and drug for synergistic effects and future potential in cancer treatment are presented and discussed. Key advances in RNA-drug anticancer synergy and localized delivery systems were combined with a review of the available literature on local co-administration of RNA and drug for cancer treatment. It is concluded that advanced delivery systems for local administration of gene-silencing RNA and drug hold potential in treatment of cancer, depending on indication. In particular, there are promising developments using pulmonary delivery and intratumoral delivery in murine models, but further research should be conducted on other local administration strategies, designs that achieve effective intracellular delivery and maximize synergy and feasibility for clinical use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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.

  2. 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.

  3. AVIDITY EVALUATION OF LOCAL IgA ANTIBODIES IN PERSONS IMMUNIZED WITH LIVE INFLUENZA VACCINE

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    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.

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

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    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.

  5. 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

  6. 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…

  7. Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity

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    Samanta Etel Treiger Borborema

    2016-04-01

    Full Text Available Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA or pentavalent antimony salt (Sb were obtained through filter extrusion (FEL and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay. The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50 of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs.

  8. 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

  9. A novel in vitro three-dimensional retinoblastoma model for evaluating chemotherapeutic drugs.

    Science.gov (United States)

    Mitra, Moutushy; Mohanty, Chandana; Harilal, Anju; Maheswari, Uma K; Sahoo, Sanjeeb Kumar; Krishnakumar, Subramanian

    2012-01-01

    Novel strategies are being applied for creating better in vitro models that simulate in vivo conditions for testing the efficacy of anticancer drugs. In the present study we developed surface-engineered, large and porous, biodegradable, polymeric microparticles as a scaffold for three dimensional (3-D) growth of a Y79 retinoblastoma (RB) cell line. We evaluated the effect of three anticancer drugs in naïve and nanoparticle-loaded forms on a 3-D versus a two-dimensional (2-D) model. We also studied the influence of microparticles on extracellular matrix (ECM) synthesis and whole genome miRNA-gene expression profiling to identify 3D-responsive genes that are implicated in oncogenesis in RB cells. Poly(D,L)-lactide-co-glycolide (PLGA) microparticles were prepared by the solvent evaporation method. RB cell line Y79 was grown alone or with PLGA-gelatin microparticles. Antiproliferative activity, drug diffusion, and cellular uptake were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole (MTT) assay, fluorescent microscope, and flow cytometry. Extra cellular matrix (ECM) synthesis was observed by collagenase assay and whole genome miRNA-microarray profiling by using an Agilent chip. With optimized composition of microparticles and cell culture conditions, an eightfold increase from the seeding density was achieved in 5 days of culture. The antiproliferative effect of the drugs in the 3-D model was significantly lower than in the 2-D suspension, which was evident from the 4.5 to 21.8 fold differences in their IC(50) values. Using doxorubicin, the flow cytometry data demonstrated a 4.4 fold lower drug accumulation in the cells grown in the 3-D model at 4 h. The collagen content of the cells grown in the 3-D model was 2.3 fold greater than that of the cells grown in the 2-D model, suggesting greater synthesis of the extracellular matrix in the 3-D model as the extracellular matrix acted as a barrier to drug diffusion. The microarray

  10. 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

  11. Unauthorized drug use in the US Army based on medical review officer evaluations.

    Science.gov (United States)

    Platteborze, Peter L; Kippenberger, Donald J; Martin, Thomas M

    2014-01-01

    This article examines the US Army's Medical Review Officer (MRO) drug positive urinalysis evaluations from 2009 through 2012. We retrospectively analyzed nearly 70,000 MRO results by year, drug and Army component. Of the MRO reviewable positive results, the Army's unauthorized drug positive rate was 22.21%. The component rates were 20.81, 24.17 and 26.09% for the Active Duty, Reserve and National Guard, respectively. By drug, the average unauthorized rates over these 4 years were 13.78% for oxycodone, 24.62% oxymorphone, 18.56% d-amphetamine, 98.04% d-methamphetamine, 21.97% codeine, 45.21% morphine and 100% steroids. In 2012 testing began for hydrocodone and hydromorphone and their unauthorized rates were 12.32 and 15.04%, respectively. The Army's unauthorized drug positive rate peaked in 2012 when it increased over 44% from the previous year. The 2012 rates in decreasing order were steroids > D-methamphetamine > morphine > oxymorphone > oxycodone > codeine > D-amphetamine > hydromorphone > hydrocodone. This comprehensive analysis showed that the majority of the Army's MRO reviews were associated with the use of authorized prescriptions; however, there appears to be significant abuse of oxycodone and D-amphetamine. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Evaluation of the Knowledge of Rural High School Students in Yazd About Drugs

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    Z Kalani

    2010-08-01

    Full Text Available Introduction: Considering high prevalence of addiction, the age range of drug abuse and availability of new synthetic drugs, evaluation of knowledge of adolescents about drugs would be a priority in research. Methods: In this descriptive cross-sectional study, 517 rural high school students were asked to complete a questionnaire and through SPSS soft ware version 13, collected data was analyzed by chi-square and analysis of variance tests. Results: 7.1% of rural families with at least one boy in high school had an addict family member. 70.2% of high school students had had a contact with an addict and 42.5% knew an adolescent addict. Also, 17.5% had been offered drugs and 37.9% of high school students claimed that there was at least one addict in their family or relations. Conclusion: Considering the frequency of addiction in families and rate of invitation to drug abuse in students, there is a high risk of increment of addiction in high schools and therefore real and urgent need to do an intervention.

  13. Quetiapine Nanoemulsion for Intranasal Drug Delivery: Evaluation of Brain-Targeting Efficiency.

    Science.gov (United States)

    Boche, Mithila; Pokharkar, Varsha

    2017-04-01

    To evaluate the possibility of improved drug delivery of quetiapine fumarate (QTP), a nanoemulsion system was developed for intranasal delivery. Effects of different HLBs of Emalex LWIS 10, PEG 400 and Transcutol P, as co-surfactants, were studied on isotropic region of pseudoternary-phase diagrams of nanoemulsion system composed of capmul MCM (CPM) as oil phase, Tween 80 as surfactant and water. Phase behaviour, globule size, transmission electron microscope (TEM) photographs and brain-targeting efficiency of quetiapine nanoemulsion were investigated. In vitro dissolution study of optimised nanoemulsion formulation, with mean diameter 144 ± 0.5 nm, showed more than twofold increase in drug release as compared with pure drug. According to results of in vivo tissue distribution study in Wistar rats, intranasal administration of QTP-loaded nanoemulsion had shorter T max compared with that of intravenous administration. Higher drug transport efficiency (DTE%) and direct nose-to-brain drug transport (DTP%) was achieved by nanoemulsion. The nanoemulsion system may be a promising strategy for brain-targeted delivery of QTP.

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

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    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.

  15. 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.

  16. Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl.

    Science.gov (United States)

    Meka, Venkata Srikanth; Songa, Ambedkar Sunil; Nali, Sreenivasa Rao; Battu, Janaki Ram; Kolapalli, Venkata Ramana Murthy

    2012-03-01

    Abstract. The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug's gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

  17. Evaluation of hydroxypropyl methylcellulose matrix systems as swellable gastro-retentive drug delivery systems (GRDDS).

    Science.gov (United States)

    Matharu, Amol S; Motto, Michael G; Patel, Mahendra R; Simonelli, Anthony P; Dave, Rutesh H

    2011-01-01

    Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic drugs by extending their transit time is a promising approach. Swellable systems were evaluated for this purpose. Such systems demonstrate dual mechanism of release-diffusion and erosion. GRDDS requires maintaining its dimensions, which demands diffusion as a predominant mechanism of release (Fickian). In this work, dypyridamole, a weakly basic drug, together with various grades of hydroxypropyl methylcellulose and different excipients were evaluated for release and swelling properties. Dissolution data were analyzed by curve fitting to various models to estimate predominant release mechanism. It was found that matrices containing a swellable diluent like microcrystalline cellulose demonstrated predominantly Fickian mechanism of release, whereas soluble diluents (lactose and mannitol) contributed to a mixed mechanism of release. Addition of copovidone increased the swelling and survivability, whereas sodium chloride altered the erosion behavior. A correlation between matrix weight loss and drug release was obtained, which further consolidated the analysis. Correlation for the soluble excipients was linear, whereas that for the swellable excipient was nonlinear, implying predominance of Fickian release mechanism for the latter. Hence, the selection of excipients can influence matrix survivability and release kinetics, which can be used for developing GRDDS. Copyright © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  18. Global and local evaluations of public speaking performance in social anxiety.

    Science.gov (United States)

    Cody, Meghan W; Teachman, Bethany A

    2011-12-01

    Differences in the relative use of global and local information (seeing the forest vs. the trees) may explain why people with social anxiety often do not benefit from corrective feedback, even though they pay close attention to details in social situations. In the current study, participants high (n=43) or low (n=47) in social anxiety symptoms gave a series of brief speeches, and then self-rated their speaking performance on items reflecting global and local performance indicators (self-assessment) and also received standardized performance feedback from an experimenter. Participants then completed a questionnaire asking how they thought the experimenter would rate their performance based on the feedback provided (experimenter assessment). Participants completed the self- and experimenter assessments again after 3 days, in addition to a measure of postevent processing (repetitive negative thinking) about their speech performance. Results showed that, as hypothesized, the High SA group rated their performance more negatively than the Low SA group. Moreover, the High SA group's ratings of global aspects of their performance became relatively more negative over time, compared to their ratings of local aspects and the Low SA group's ratings. As expected, postevent processing mediated the relationship between social anxiety group status and worsening global performance evaluations. These findings point to a pattern of progressively more negative global evaluations over time for persons high in social anxiety. Copyright © 2011. Published by Elsevier Ltd.

  19. Global and Local Evaluations of Public Speaking Performance in Social Anxiety

    Science.gov (United States)

    Cody, Meghan W.; Teachman, Bethany A.

    2012-01-01

    Differences in the relative use of global and local information (seeing the forest versus the trees) may explain why people with social anxiety often do not benefit from corrective feedback, even though they pay close attention to details in social situations. In the current study, participants high (n = 43) or low (n = 47) in social anxiety symptoms gave a series of brief speeches, and then self-rated their speaking performance on items reflecting global and local performance indicators (self assessment) and also received standardized performance feedback from an experimenter. Participants then completed a questionnaire asking how they thought the experimenter would rate their performance based on the feedback provided (experimenter assessment). Participants completed the self and experimenter assessments again after three days, in addition to a measure of post-event processing (repetitive negative thinking) about their speech performance. Results showed that, as hypothesized, the high social anxiety group rated their performance more negatively than the low social anxiety group did. Moreover, the high social anxiety group’s ratings of global aspects of their performance became relatively more negative over time, compared to their ratings of local aspects and the low social anxiety group’s ratings. As expected, post-event processing mediated the relationship between social anxiety group status and worsening global performance evaluations. These findings point to a pattern of progressively more negative global evaluations over time for persons high in social anxiety. PMID:22035989

  20. Local media monitoring in process evaluation. Experiences from the Stockholm Diabetes Prevention Programme.

    Science.gov (United States)

    Andersson, Camilla Maria; Bjärås, Gunilla; Tillgren, Per; Ostenson, Claes-Göran

    2007-01-01

    We present a rationale and approach for longitudinal analyses of media coverage and content, and illustrate how media monitoring can be used in process evaluations. Within a community-based diabetes prevention project, the Stockholm Diabetes Prevention Program, we analyzed the frequency, prominence, and framing of physical activity in local newspapers of three intervention and two control municipalities. In total, 2,128 stories and advertisements related to physical activity were identified between the years 1997 and 2002. Although stories about physical activity were relatively few (n = 224), they were prominently located in all five local newspapers. Physical activity was framed rather similarly in the municipalities. Health aspects, however, were expressed to a greater extent in stories in two of the intervention municipalities. A limited portion (14%) of the articles could be linked directly to the program. It is not possible to assess to what extent the program has had a disseminating effect on the newspapers' health-related content in general, due to weaknesses of the process tracking system and limitations of the study design. Implications for the design is that an evaluative framework should be preplanned and include data collection about media relationships, media's interest in public health, media coverage prior to the program and coverage in other media for comparisons of general trends in the reporting. The material and the current database, however, provide a good basis for quantitative content analysis and qualitative discourse analysis to yield information on the type, frequency, and content of health reporting in local newspapers.

  1. 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.

  2. [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.

  3. 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

  4. 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....... 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...

  5. 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...

  6. Damage localization by statistical evaluation of signal-processed mode shapes

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Damkilde, Lars

    2015-01-01

    in the spatial mode shape signals, hereby potentially facilitating damage detection and/or localization. However, by being based on distinguishing damage-induced discontinuities from other signal irregularities, an intrinsic deficiency in these methods is the high sensitivity towards measurement noise....... The present article introduces a damage localization method which, compared to the conventional mode shape-based methods, has greatly enhanced robustness towards measurement noise. The method is based on signal processing of spatial mode shapes by means of continuous wavelet transformation (CWT......) and subsequent application of a generalized discrete Teager-Kaiser energy operator (GDTKEO) to identify damage-induced mode shape discontinuities. In order to evaluate whether the identified discontinuities are in fact damage-induced, outlier analysis of principal components of the signal-processed mode shapes...

  7. Synthesis and Evaluation of Paclitaxel-Loaded Gold Nanoparticles for Tumor-Targeted Drug Delivery.

    Science.gov (United States)

    Paciotti, Giulio F; Zhao, Jielu; Cao, Shugeng; Brodie, Peggy J; Tamarkin, Lawrence; Huhta, Marja; Myer, Lonnie D; Friedman, Jay; Kingston, David G I

    2016-11-16

    The synthesis of a series of thiolated paclitaxel analogs is described as part of a novel nanomedicine program aimed at developing formulations of paclitaxel that will bind to gold nanoparticles for tumor targeted drug delivery. Preliminary evaluation of the new nanomedicine composed of 27 nm gold nanoparticles, tumor necrosis factor alpha (TNFα), thiolated polyethylene glycol (PEG-thiol), and one of several thiolated paclitaxel analogs is presented.

  8. Evaluation of parenteral drugs for anesthesia in the blue crab (Callinectes sapidus).

    Science.gov (United States)

    Quesada, Rolando J; Smith, Christopher D; Heard, Darryl J

    2011-06-01

    The objective of this study was to evaluate the efficacy and safety of several parenteral anesthetics in blue crabs (Callinectes sapidus). Thirty-one animals were administered one or more of the following drugs by injection into the hemolymph (i.v.) through an arthrodial membrane: etomidate, ketamine, lidocaine, pentobarbital, propofol, tiletamine-zolazepam, xylazine, and ketamine-xylazine. A subset of crabs received intracardiac ketamine. Etomidate had no effect. Lidocaine effects were ultrashort (sapidus as well as in other crab species.

  9. COMPARATIVE IN VITRO QUALITY EVALUATION OF SOME PARACETAMOL TABLETS, COMMERCIALLY AVAILABLE IN BANGLADESH DRUG MARKET

    OpenAIRE

    Jannatul Farhana, Md. Najem Uddin*, Md. Robiul Islam

    2018-01-01

    Paracetamol is a widely used non-prescription analgesic and antipyretic medicine. It is one of the most commonly used drugs worldwide with non-prescription sales exceeding 25 thousand million doses per year in the United States of America. The study was conducted to assess the comparative in-vitro quality control parameters through the evaluation of weight variation, hardness, friability, disintegration time and dissolution profile among the commercially available tablet brands of paracetamol...

  10. Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation.

    Science.gov (United States)

    Li, Zhen; Cao, Jinxu; Li, Heran; Liu, Hongzhuo; Han, Fei; Liu, Zhenyun; Tong, Chao; Li, Sanming

    2016-10-01

    Orgnaogels based on amino acid derivatives have been widely used in the area of drug delivery. An organogel system based on l-lysine derivatives was designed and prepared to induce a thermal sensitive implant with higher transition temperature, better mechanical strength, and shorter gelation time. The organogel was prepared by injectable soybean oil and methyl (S)-2,5-ditetradecanamidopentanoate (MDP), which was synthesized for the first time. Candesartan cilexetil (CC) was chosen as model drug. Different formulations were designed and optimized by response surface method. Thermal, rheology properties, and gelation kinetics of the optimized formulation had been characterized. The release behaviors in vitro, as well as in vivo were evaluated in comparison with the oily solution of drugs. Finally, the local inflammation response of in situ organogel was assessed by histological analysis. Results showed that the synthesized gelator, MDP, had a good gelation ability and the organogels obtained via the self-assembly of gelators in vegetable oils exhibited great thermal and rheology properties, which guaranteed their state in body. In vivo pharmacokinetic demonstrated that the organogel formulation could extend the drug release and maintain a therapeutically effective plasma concentration at least 10 d. In addition, this implant showed acceptable moderate inflammation. The in situ forming l-lysine-derivative-based organogel could be a promising matrix for sustained drug delivery of the drugs with low solubility.

  11. Evaluation involvement of local HIV/AIDS non-governmental organisations in Benin

    Directory of Open Access Journals (Sweden)

    Maurice T. Agonnoude

    2016-06-01

    Full Text Available Background: For some years, non-governmental organisations (NGOs and civil society have become increasingly involved in the fight against the HIV/AIDS pandemic in Africa. But even though their role is well appreciated, their actions are perceived as ineffective because of a lack of monitoring and evaluation capacity.Objective: This paper aims to describe local HIV/AIDS NGOs’ involvement in evaluation and the characteristics of this involvement.Method: Descriptive analysis of data collected in questionnaires completed by 34 NGO executives (one per NGO.Results: Most NGOs do not have the minimal conditions required for positive and effective involvement in evaluations. In addition, funding agencies’ expectations for evaluations, total human resources as well as experience as NGO are contextual factors that explain most aspects of their involvement in evaluations.Conclusion: This study provides funding agencies, NGO leaders and all those interested in developing evaluation capacity in these NGOs to understand the extent of the task in this area. They must keep in mind that there is no solution for all, but that solutions must be adapted to the developmental level of each organisation.

  12. 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.

  13. 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)

    2014-01-01

    phenomena. As a result, recruitment and data 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. Conclusions 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. PMID:24520885

  14. A useful tool for drug interaction evaluation: The University of Washington Metabolism and Transport Drug Interaction Database

    Directory of Open Access Journals (Sweden)

    Hachad Houda

    2010-10-01

    Full Text Available Abstract The Metabolism and Transport Drug Interaction Database (http://www.druginteractioninfo.org is a web-based research and analysis tool developed in the Department of Pharmaceutics at the University of Washington. The database has the largest manually curated collection of data related to drug interactions in humans. The tool integrates information from the literature, public repositories, reference textbooks, guideline documents, product prescribing labels and clinical review sections of new drug approval (NDA packages. The database's easy-to-use web portal offers tools for visualisation, reporting and filtering of information. The database helps scientists to mine kinetics information for drug-metabolising enzymes and transporters, to assess the extent of in vivo drug interaction studies, as well as case reports for drugs, therapeutic proteins, food products and herbal derivatives. This review provides a brief description of the database organisation, its search functionalities and examples of use.

  15. Evaluation of local media surveillance for improved disease recognition and monitoring in global hotspot regions.

    Directory of Open Access Journals (Sweden)

    Jessica S Schwind

    Full Text Available Digital disease detection tools are technologically sophisticated, but dependent on digital information, which for many areas suffering from high disease burdens is simply not an option. In areas where news is often reported in local media with no digital counterpart, integration of local news information with digital surveillance systems, such as HealthMap (Boston Children's Hospital, is critical. Little research has been published in regards to the specific contribution of local health-related articles to digital surveillance systems. In response, the USAID PREDICT project implemented a local media surveillance (LMS pilot study in partner countries to monitor disease events reported in print media. This research assessed the potential of LMS to enhance digital surveillance reach in five low- and middle-income countries. Over 16 weeks, select surveillance system attributes of LMS, such as simplicity, flexibility, acceptability, timeliness, and stability were evaluated to identify strengths and weaknesses in the surveillance method. Findings revealed that LMS filled gaps in digital surveillance network coverage by contributing valuable localized information on disease events to the global HealthMap database. A total of 87 health events were reported through the LMS pilot in the 16-week monitoring period, including 71 unique reports not found by the HealthMap digital detection tool. Furthermore, HealthMap identified an additional 236 health events outside of LMS. It was also observed that belief in the importance of the project and proper source selection from the participants was crucial to the success of this method. The timely identification of disease outbreaks near points of emergence and the recognition of risk factors associated with disease occurrence continue to be important components of any comprehensive surveillance system for monitoring disease activity across populations. The LMS method, with its minimal resource commitment, could

  16. Evaluation of local media surveillance for improved disease recognition and monitoring in global hotspot regions.

    Science.gov (United States)

    Schwind, Jessica S; Wolking, David J; Brownstein, John S; Mazet, Jonna A K; Smith, Woutrina A

    2014-01-01

    Digital disease detection tools are technologically sophisticated, but dependent on digital information, which for many areas suffering from high disease burdens is simply not an option. In areas where news is often reported in local media with no digital counterpart, integration of local news information with digital surveillance systems, such as HealthMap (Boston Children's Hospital), is critical. Little research has been published in regards to the specific contribution of local health-related articles to digital surveillance systems. In response, the USAID PREDICT project implemented a local media surveillance (LMS) pilot study in partner countries to monitor disease events reported in print media. This research assessed the potential of LMS to enhance digital surveillance reach in five low- and middle-income countries. Over 16 weeks, select surveillance system attributes of LMS, such as simplicity, flexibility, acceptability, timeliness, and stability were evaluated to identify strengths and weaknesses in the surveillance method. Findings revealed that LMS filled gaps in digital surveillance network coverage by contributing valuable localized information on disease events to the global HealthMap database. A total of 87 health events were reported through the LMS pilot in the 16-week monitoring period, including 71 unique reports not found by the HealthMap digital detection tool. Furthermore, HealthMap identified an additional 236 health events outside of LMS. It was also observed that belief in the importance of the project and proper source selection from the participants was crucial to the success of this method. The timely identification of disease outbreaks near points of emergence and the recognition of risk factors associated with disease occurrence continue to be important components of any comprehensive surveillance system for monitoring disease activity across populations. The LMS method, with its minimal resource commitment, could be one tool used to

  17. 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)

  18. Evaluation of health plan member use of an online prescription drug price comparison tool.

    Science.gov (United States)

    Carroll, Norman V; Mitchell, Matthew P; Cannon, H Eric; York, Bryan W York; Oscar, Robert S

    2010-01-01

    Health plans have implemented tiered copayment systems to incentivize members to use less expensive medications. However, members need drug price information to make comparisons among therapeutic alternatives. Many health plans and pharmacy benefit management companies have implemented online prescription drug price comparison tools to provide such information. There has been little published evaluation of these tools. To evaluate use of an online price comparison tool- MyPharmacyTools (MPT)- by the measures of (a) the extent to which the tool was used, (b) changes in use over the first year after implementation, and (c) the types of members who were most likely to use the tool. Data were provided by a 500,000-member integrated health plan with approximately 156,250 enrolled families. The sample included only families with continuous eligibility for all members from July 1, 2006, through June 30, 2008; use of 1 of 7 common copayment structures; and use of the pharmacy benefit in every quarter of the study period. Data collected on each member, using pharmacy claims for the time period July 1, 2007, through June 30, 2008, included annual drug costs (total, out-of-pocket, plan-paid, and mail order) and number of unique drugs and unique generic drugs taken during the third quarter of 2007. Data collected also included whether the member had each of several selected chronic diseases (as inferred from drug claims for the third quarter of 2007) and demographics. Age, gender, and family size were taken from eligibility files. Other demographic data were imputed to members from the demographics of the ZIP code in which they resided. MPT was made available to members on July 1, 2007. Use of MPT was measured as the number of times members logged into the site for each quarter during the subsequent year. Statistical analyses were conducted at the family rather than at the individual level, and families were defined as users if any family member used MPT at least once during

  19. 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.

  20. 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.

  1. Evaluation of the potential for a pharmacokinetic drug-drug interaction between armodafinil and ziprasidone in healthy adults.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Yang, Ronghua; Hellriegel, Edward T; Robertson, Philmore

    2014-10-01

    Armodafinil has been studied as adjunctive therapy for major depressive episodes associated with bipolar I disorder. This open-label, single-centre, 2-period study evaluated the effect of armodafinil, a moderate inducer of cytochrome-P450 (CYP) isoenzyme CYP3A4, on the pharmacokinetics and safety of ziprasidone, an atypical antipsychotic used to treat bipolar I disorder and metabolized in part by CYP3A4. Thirty-five healthy subjects received ziprasidone (20 mg) alone and after armodafinil pretreatment (titrated to 250 mg/day); of those, 25 were evaluable for pharmacokinetics. Pharmacokinetic parameters were derived from plasma concentrations of ziprasidone collected prior to and over the 48 h after each ziprasidone administration. Plasma concentrations of armodafinil and its circulating metabolites, R-modafinil acid and modafinil sulfone, were also obtained after repeated daily dosing of armodafinil alone. Safety and tolerability were assessed. Systemic exposure to ziprasidone was similar following administration alone or after pretreatment with armodafinil, as assessed by mean peak plasma concentration (C max, 52.1 vs 50.4 ng/mL) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞, 544.6 vs 469.1 ng·h/mL). Geometric mean ratios of systemic exposure (ziprasidone alone: ziprasidone after pretreatment with armodafinil) were close to unity, with associated 90 % confidence intervals (CIs) within the range of 0.80-1.25 (C max, 0.97; 90 % CI, 0.87-1.08; AUC0-∞, 0.86; 90 % CI, 0.82-0.91). Adverse events were consistent with the known safety profiles of each agent. Systemic exposure to ziprasidone was not affected by pretreatment with armodafinil. Both drugs were generally safe and well tolerated under the conditions studied.

  2. Association of Localized Hypersensitivity and In-Stent Neoatherosclerosis with the Very Late Drug-Eluting Stent Thrombosis

    Science.gov (United States)

    Yamaji, Kyohei; Kubo, Shunsuke; Inoue, Katsumi; Kadota, Kazushige; Kuramitsu, Shoichi; Shirai, Shinichi; Ando, Kenji; Nobuyoshi, Masakiyo; Mitsudo, Kazuaki; Kimura, Takeshi

    2014-01-01

    Background 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. Methods and Results 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. Conclusions 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. PMID:25423451

  3. 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.

  4. [Evaluation of public drug provision policies for type 2 diabetes mellitus in Argentina: a case study].

    Science.gov (United States)

    Elorza, María Eugenia; Moscoso, Nebel Silvana; Ripari, Nadia Vanina

    2012-01-01

    In Argentina, the provision of drugs for patients suffering from type 2 diabetes mellitus who lack health insurance is carried out through public programs. In the Province of Buenos Aires, the national program Remediar and the provincial program PRODIABA (from the Spanish Programa de Prevención, Diagnóstico y Tratamiento del Paciente Diabético) coexist. This study estimates the percentage of adults in the municipality of Bahia Blanca (Province of Buenos Aires) who suffer from type 2 diabetes mellitus and lack health insurance, thus satisfying their need for oral antidiabetic treatments within the public sector. It is a quantitative study that assesses the need and demand for public provision. The results indicate that: 1) the greatest percentage of demand is satisfied at the primary health care level; 2) the province of Buenos Aires funds the largest share of the pills, followed by the municipal and the national levels; 3) the local government intervenes to satisfy the demand and 4) the total public provision covers approximately 25% of the overall need in relation to the average consumption. This shows that despite the presence of these public programs, the provision is insufficient and thus requires the intervention of the local government even though economic theory does not recommend the decentralization of drug purchases.

  5. 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.

  6. 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.

  7. 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.

  8. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Christensen, A H; Andersen, C B; Tybjærg-Hansen, A

    2011-01-01

    Christensen AH, Andersen CB, Tybjærg-Hansen A, Haunso S, Svendsen JH. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right...... ventricular cardiomyopathy (ARVC). We aimed at performing mutational analysis of the gene and characterizing the associated immunohistochemical features. Sixty-five unrelated patients (55 fulfilling Task Force criteria and 10 borderline cases) were screened for mutations in TMEM43. Immunohistochemistry...

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

    Directory of Open Access Journals (Sweden)

    Morteza Eskandani

    2011-08-01

    Full Text Available 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.

  10. Comet assay: a method to evaluate genotoxicity of nano-drug delivery system.

    Science.gov (United States)

    Vandghanooni, Somayeh; Eskandani, Morteza

    2011-01-01

    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. In the current study, we reviewed recent drug delivery researches related to SCGE. 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''. 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.

  11. 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

  12. 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

  13. 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.

  14. Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds.

    Science.gov (United States)

    Martin, Baptiste; Brouillet, Fabien; Franceschi, Sophie; Perez, Emile

    2017-05-01

    The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.

  15. 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.

  16. An in-vivo evaluation of a MEMS drug delivery device using Kunming mice model.

    Science.gov (United States)

    Liu, Yaqian; Song, Peiyi; Liu, Jianwei; Tng, Danny Jian Hang; Hu, Rui; Chen, Hongyan; Hu, Yazhuo; Tan, Cher Heng; Wang, Jianhua; Liu, Jing; Ye, Ling; Yong, Ken-Tye

    2015-02-01

    The use of MEMS implantable drug delivery pump device enables one to program the desired drug delivery profile in the device for individualized medicine treatment to patients. In this study, a MEMS drug delivery device is prepared and employed for in vivo applications. 12 devices are implanted subcutaneously into Kunming mice for evaluating their long term biocompatibility and drug-delivery efficiency in vivo. All the mice survived after device implantation surgery procedures. Histological analysis result reveals a normal wound healing progression within the tissues-to-device contact areas. Serum analysis shows that all measured factors are within normal ranges and do not indicate any adverse responses associated with the implanted device. Phenylephrine formulation is chosen and delivered to the abdominal cavity of the mice by using either the implanted MEMS device (experimental group) or the syringe injection method (control group). Both groups show that they are able to precisely control and manipulate the increment rate of blood pressure in the small animals. Our result strongly suggests that the developed refillable implantable MEMS devices will serve as a viable option for future individualized medicine applications such as glaucoma, HIV-dementia and diabetes therapy.

  17. In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery

    Science.gov (United States)

    Rahimi, Maham; Wadajkar, Aniket; Subramanian, Khaushik; Yousef, Monet; Cui, Weina; Hsieh, Jer-Tsong; Nguyen, Kytai

    2010-01-01

    Previously uncharacterized poly(N-isopropylacrylamide-acrylamide-allylamine)-coated magnetic nanoparticles (MNPs) were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Properties of these nanoparticles such as size, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. Spherical core-shell nanoparticles with a diameter of 100 nm showed significantly lower systemic toxicity than did bare MNPs, as well as doxorubicin encapsulation efficiency of 72%, and significantly higher doxorubicin release at 41°C compared with 37°C, demonstrating their temperature sensitivity. Released drugs were also active in destroying prostate cancer cells (JHU31). Furthermore, the nanoparticle uptake by JHU31 cells was dependent on dose and incubation time, reaching saturation at 500 μg/mL and 4 hours, respectively. In addition, magnetic resonance imaging capabilities of the particles were observed using agarose platforms containing cells incubated with nanoparticles. Future work includes investigation of targeting capability and effectiveness of these nanoparticles in vivo using animal models. PMID:20172050

  18. New anticoagulant drugs versus warfarin in atrial fibrillation: economic evaluation and cost-effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Mauro Silingardi

    2013-12-01

    Full Text Available Health care resources available for medical procedures, including pharmaceuticals, are limited worldwide. Health economic evidence is now accepted as an essential component of health technology appraisal, realizing the importance of value for money considerations for a more efficient (cost-effective prescribing. Regulatory agencies in more and more countries perform economic evaluation and cost-effectiveness analysis in order to decide about reimbursement of a new and almost always more expensive drug. Pharmacoeconomy is now acknowledged as a science. Cost-effective analysis is just one of its approaches, measuring cost in money and benefit in terms of Quality Adjusted Life Year, a new outcome measure which combines quantity/quality of additional life-years gained with the new drug/technology. A growing body of pharmacoeconomic evidence about new anticoagulant drugs (dabigatran, rivaroxaban, apixaban for stroke prevention in atrial fibrillation is now available. Most of this evidence comes from the National Institute of Health and Clinical Excellence (NICE in the United Kingdom, the most referenced regulatory agency in the world. Compared to current standard therapies (warfarin, dabigatran, rivaroxaban and apixaban are cost-effective treatments for the whole population of patients with atrial fibrillation, independently of poor/good international normalized ratio control (time in therapeutic range and risk stratification for stroke (CHADS2 score. Significant innovation and the lower rate of intracranial hemorrhage/hemorrhagic stroke coupled with the new drugs are the key drivers of these results.

  19. Immunological Evaluation of Two Local Isolates of Eimeria tenella Gametocytes against Coccidiosis in Poultry

    Directory of Open Access Journals (Sweden)

    Masood Akhtar*, M. Irfan Anwar, Zafar Iqbal, Faqir Muhammad1, Mian Muhammad Awais, Ahsan ul Haq2 and Elzbieta Hiszczynska-Sawicka3

    2012-01-01

    Full Text Available Two local isolates of Eimeria tenella gametocytes against coccidiosis were immunologically evaluated in chickens. Cell mediated immune response was detected by modified splenic cell migration inhibition assay (MSCMIA and data were expressed in terms of per cent migration index. No significant difference in per cent migration index was detected for the chickens immunized either with Vaccine-I (local isolate-I or with Vaccine-II (local isolate-II; however per cent migration index was comparatively lower in chickens immunized with Vaccine-II as compared to Vaccine-I; indicating a somewhat higher cell mediated immune (CMI response. Humoral immune response was monitored by ELISA in vaccinated and control chickens. Significantly elevated (P<0.05 antibody titer (IgG in chickens immunized with Vaccine-II as compared to Vaccine-I was detected. Significantly higher protection (67% in chickens immunized with Vaccine-II followed by vaccine-I (49% was recorded. Further, oocyst count was significantly lower (P<0.05 in chickens immunized with Vaccine-II as compared to those immunized with Vaccine-I. It was concluded that vaccinal strain (Vaccine-II contained additional protein of high molecular weight (49.23 kDa in its gametocytes provided cross protection and can be used to prepare commercial vaccine against coccidiosis in poultry.

  20. 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.

  1. 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.

  2. 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.

  3. Medication Reconciliation and Evaluation of Drug Discrepancies by a Pharmacist in Omid Hospital, Lali, Khouzestan

    Directory of Open Access Journals (Sweden)

    Leila Kouti

    2017-09-01

    Full Text Available Background: Medication discrepancies occur at the time of medicine prescription in inpatient and outpatient settings, especially at patient transfer and discharge. Pharmacists can prevent these medication errors by reconciliation of the patients’ medications. In this study, medication discrepancies of the only hospital of a small town are assessed by a pharmacist.Methods:A medication reconciliation form was designed to fully record all patients’ drug history and current therapies. All admitted patients during a six month interval were evaluated by a pharmacist and their medical records were compared to the detailed data form.Results:150 admitted patients were evaluated in this study from September 2015 to February 2016. 51% of the patients were male and 49% female. 56% of the patients had medication discrepancies when discharged. Interestingly none of the patients had documented drug history in their medical records.Conclusion:More than half of the patients developed a medication discrepancy at the time of discharge. We think that a drug review of the patients at the time of admission and discharge and establishing medication reconciliation processes may be helpful in improvement of health care.

  4. 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.

  5. Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets.

    Science.gov (United States)

    Shojaee, Saeed; Nokhodchi, Ali; Maniruzzaman, Mohammed

    2017-02-01

    Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected. Graphical abstract ᅟ.

  6. 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 block with ropivacaine.

  7. 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.

  8. 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.

  9. Evaluation of chemically modified hydrophobic sago starch as a carrier for controlled drug delivery.

    Science.gov (United States)

    Singh, Akhilesh Vikram; Nath, Lila Kanta

    2013-04-01

    The present investigation deals with the development of controlled release tablets of lamivudine using acetylated sago starch. The acetylated starch was synthesized with acetic anhydride in pyridine medium. The acetylated sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulations were evaluated for physical characteristics like hardness, % friability, % drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in the case of higuchi kinetic model and the release mechanism study proved that the formulation showed a combination of diffusion and erosion processes. There was a significant difference in the pharmacokinetic parameters (T max, C max, AUC, V d, T 1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir® which proves the controlled release property of acetylated sago starch.

  10. 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.

  11. Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis

    Directory of Open Access Journals (Sweden)

    Baskar Nammalwar

    2014-03-01

    Full Text Available Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against Bacillus anthracis. The structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an N-acryloyl-substituted 1,2-dihydrophthalazine ring. Various changes were made at the C1 stereocenter of the dihydrophthalazine moiety in the structure, and the biological activity was assessed by measurement of the MIC and Ki values to identify the most potent drug candidate.

  12. Evaluating the predictivity of virtual screening for ABL kinase inhibitors to hinder drug resistance

    DEFF Research Database (Denmark)

    Gani, Osman A B S M; Narayanan, Dilip; Engh, Richard A

    2013-01-01

    Virtual screening methods are now widely used in early stages of drug discovery, aiming to rank potential inhibitors. However, any practical ligand set (of active or inactive compounds) chosen for deriving new virtual screening approaches cannot fully represent all relevant chemical space...... for potential new compounds. In this study, we have taken a retrospective approach to evaluate virtual screening methods for the leukemia target kinase ABL1 and its drug-resistant mutant ABL1-T315I. 'Dual active' inhibitors against both targets were grouped together with inactive ligands chosen from different...... component analyses of chemical properties, can distinguish some decoy sets from active compounds, the addition of target structural information via docking improves enrichment, and explicit consideration of multiple target conformations (i.e. types I and II) achieves best enrichment of active versus...

  13. ASSESSING THE PATTERN OF DRUG USE AMONG PREGNANT WOMEN AND EVALUATING THE IMPACT OF COUNSELLING ON MEDICATION ADHERENCE AMONG THEM

    OpenAIRE

    Banda Shalini Reddy; NeelkantReddy Patil; Hinchageri S. S; Swarna kamala

    2011-01-01

    In the present study an attempt is made to assess the pattern of drug use among pregnant women and to evaluate the impact of counseling on medication adherence by providing patient education regarding pregnancy. During the study period pregnant women were enrolled in the study after obtaining consent from them. The prescriptions containing atleast one drug were analyzed and the drugs prescribed were classified according to their pharmacological class. Analysis of prescription patterns did not...

  14. 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.

  15. Drug solubilization and in vitro toxicity evaluation of lipoamino acid surfactants.

    Science.gov (United States)

    Ménard, Nathalie; Tsapis, Nicolas; Poirier, Cécile; Arnauld, Thomas; Moine, Laurence; Lefoulon, François; Péan, Jean-Manuel; Fattal, Elias

    2012-02-28

    To improve solubilization of a water insoluble anticancer drug, novel surfactants were synthesized. All surfactants derived from lysine, with a so-called nitrilo triacetic acid (NTA) polar head, and differed from the length and saturation degree of their hydrophobic moieties: C19:0-NTA, C20:4-NTA, C25:0-NTA and C25:4-NTA. Self-assembling properties and critical micellar concentration (CMC) values were determined using pyrene fluorescence and cytotoxicity using MTT and LDH assays on endothelial cells. Surfactant haemolytic activity and drug solubilization capacity were also evaluated. All surfactants self-assemble with low CMC values from 0.012 to 0.430 mg/mL. Cytotoxicity assays showed that C20:4-NTA and C25:0-NTA were less cytotoxic than polysorbate 80. Unsaturations and alkane chain length have a marked influence on toxicity. Saturated surfactants had a similar haemolytic activity, explained by their low CMC values and the linear configuration of their hydrophobic tail. C20:4-NTA and C25:4-NTA were less haemolytic than polysorbate 80. Furthermore, C19:0-NTA, C25:0-NTA and C25:4-NTA increased drug solubility from <0.15 μg/mL up to 7 mg/mL, with 46% (w/w) drug loading, due to their linear and flexible hydrophobic chain configuration, as evidenced by molecular modelling. Although these solubilizers are promising, a compromise between drug solubilization and toxicity remains to be found. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. In vivo evaluation of drug-drug interactions linked to UGT inhibition: the effect of probenecid on dalcetrapib pharmacokinetics.

    Science.gov (United States)

    Aceves Baldó, Pau; Anzures-Cabrera, Judith; Bentley, Darren

    2013-03-01

    To assess the effect of the UGT inhibitor probenecid on the pharmacokinetics of dalcetrapib, an investigational drug whose pharmacologically active thiol form undergoes glucuronidation (fm UGT ≥ 0.25). A two-way crossover study in 20 healthy subjects. Subjects received a single 600 mg dose of dalcetrapib with or without probenecid (500 mg 4 times daily for 6 days). AUC∞ and Cmax of dalcetrapib thiol were increased by 14% and 21%, respectively, by co-administration of probenecid. This case study illustrates the difficulty in predicting clinically relevant drug-drug interactions for UGT substrates based only on the fraction metabolized by glucuronidation.

  17. Evaluation of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs according to the latest classification.

    Science.gov (United States)

    Demir, S; Olgac, M; Unal, D; Gelincik, A; Colakoglu, B; Buyukozturk, S

    2015-11-01

    The consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) proposed by the European Network for Drug Allergy (ENDA) interest group (2011) was revised in 2013. We aimed to evaluate the usability of the latest NSAID hypersensitivity classification of ENDA. A total of 370 patients with a history of hypersensitivity reactions to NSAIDs among the 1250 outpatients referred for suspected drug allergy between July 2013 and June 2014 were evaluated, and 308 patients who were confirmed as having NSAID hypersensitivity were included in this study. After confirming the diagnosis, a single-blind placebo-controlled drug provocation test was performed with aspirin or diclofenac to categorize the patients according to the ENDA classification. The reactions not meeting the ENDA classification criteria were grouped as blended reactions. Among the 308 patients (224 female, mean age 42.12 ± 13.24), the leading cause of hypersensitivity reactions was metamizol (30.5%) followed by aspirin (30.2%). The most common NSAID hypersensitivity subgroup was SNIUAA (46.4%) and the least common type was SNIDR (1.6%). Cross-reactivity was identified in 50.3% of the patients. In five patients (1.6%), the hypersensitivity reactions to NSAIDs did not meet the ENDA classification: Three patients experienced anaphylaxis with different NSAIDs, one patient encountered anaphylaxis with one NSAID and urticaria with other NSAIDs, and the last patient had angioedema with different NSAIDs. The latest ENDA classification for NSAID hypersensitivity is generally a practical and useful instrument for clinicians. We only point out that anaphylaxis with different NSAIDs can be seen in a small group of patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program

    Science.gov (United States)

    Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

    2012-01-01

    Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

  19. In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1.

    Science.gov (United States)

    Pak, Y Anne; Long, Amanda J; Annes, William F; Witcher, Jennifer W; Knadler, Mary Pat; Ayan-Oshodi, Mosun A; Mitchell, Malcolm I; Leese, Phillip; Hillgren, Kathleen M

    2017-02-01

    Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design. In vitro investigations determined the prodrug (LY2140023 monohydrate) is a substrate of PEPT1 with K m value of approximately 30 µM, whereas the active moiety (LY404039) is not a PEPT1 substrate. In addition, among the eight known PEPT1 substrates evaluated in vitro, valacyclovir was the most potent inhibitor (IC 50 = 0.46 mM) of PEPT1-mediated uptake of the prodrug. Therefore, a clinical drug interaction study was conducted to evaluate the potential interaction between the prodrug and valacyclovir in healthy subjects. No effect of coadministration was observed on the pharmacokinetics of the prodrug, valacyclovir, or either of their active moieties. Although in vitro studies showed potential for the prodrug and valacyclovir interaction via PEPT1, an in vivo study showed no interaction between these two drugs. PEPT1 does not appear to easily saturate because of its high capacity and expression in the intestine. Thus, a clinical interaction at PEPT1 is unlikely even with a compound with high affinity for the transporter. Copyright © 2017 by The Author(s).

  20. Cholinergic mechanisms in canine narcolepsy--I. Modulation of cataplexy via local drug administration into the pontine reticular formation.

    Science.gov (United States)

    Reid, M S; Tafti, M; Geary, J N; Nishino, S; Siegel, J M; Dement, W C; Mignot, E

    1994-04-01

    Cataplexy in the narcoleptic canine has been shown to increase after systemic administration of cholinergic agonists. Furthermore, the number of cholinergic receptors in the pontine reticular formation of narcoleptic canines is significantly elevated. In the present study we have investigated the effects of cholinergic drugs administered directly into the pontine reticular formation on cataplexy, as defined by brief episodes of hypotonia induced by emotions, in narcoleptic canines. Carbachol and atropine were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of freely moving, narcoleptic and control Doberman pinschers. Cataplexy was quantified using the Food-Elicited Cataplexy Test, and analysed using recordings of electroencephalogram, electrooculogram and electromyogram. Cataplexy was characterized by a desynchronized electroencephalogram and a drop in electromyogram and electrooculogram activity. In narcoleptic canines, both unilateral and bilateral carbachol (10(-5) to 10(-3) M) produced a dose-dependent increase in cataplexy, which resulted in complete muscle tone suppression at the highest concentration. In control canines, neither bilateral nor unilateral carbachol (10(-5) to 10(-3) M) produced cataplexy, although bilateral carbachol, did produce muscle atonia at the highest dose (10(-3)). The increase in cataplexy after bilateral carbachol (10(-4) M) was rapidly reversed when the perfusion medium was switched to one containing atropine (10(-4) M). Bilateral atropine (10(-3) to 10(-2) M) alone did not produce any significant effects on cataplexy in narcoleptic canines; however, bilateral atropine (10(-2) M) did reduce the increase in cataplexy produced by systemic administration of physostigmine (0.05 mg/kg, i.v.). These findings demonstrate that cataplexy in narcoleptic canines can be stimulated by applying cholinergic agonists directly into the pontine reticular formation. The ability of atropine to inhibit

  1. [Evaluation of potential drug interactions in primary health care prescriptions in Vitória da Conquista, Bahia (Brazil)].

    Science.gov (United States)

    Leão, Danyllo Fábio Lessa; de Moura, Cristiano Soares; de Medeiros, Danielle Souto

    2014-01-01

    Drug interactions are risk factors for the occurrence of adverse drug reactions. The risk for drug interactions includes factors related to prescription that are intrinsic to the patient. This study sought to evaluate the potential drug interactions in primary care prescriptions in Vitória da Conquista in the state of Bahia to fill the knowledge gap on this topic in Brazil. Information about several variables derived from the primary health care prescriptions was collected and drug interactions were evaluated based on information from Medscape and Micromedex(R) databases. Polypharmacy frequency and its association with the occurrence of drug interactions were also evaluated. Results revealed a 48,9% frequency of drug interactions, 74,9% of moderate or greater severity, 8,6% of prescriptions in polypharmacy that in the chi-square test showed a positive association with the occurrence of drug interactions (p Conquista in the state of Bahia showed a high frequency of drug interactions, however it is necessary to analyze other risk factors for their occurrence at this level of health care.

  2. Challenges in evaluating cancer as a clinical outcome in postapproval studies of drug safety.

    Science.gov (United States)

    Pinheiro, Simone P; Rivera, Donna R; Graham, David J; Freedman, Andrew N; Major, Jacqueline M; Penberthy, Lynne; Levenson, Mark; Bradley, Marie C; Wong, Hui-Lee; Ouellet-Hellstrom, Rita

    2016-11-01

    Pharmaceuticals approved in the United States are largely not known human carcinogens. However, cancer signals associated with pharmaceuticals may be hypothesized or arise after product approval. There are many study designs that can be used to evaluate cancer as an outcome in the postapproval setting. Because prospective systematic collection of cancer outcomes from a large number of individuals may be lengthy, expensive, and challenging, leveraging data from large existing databases are an integral approach. Such studies have the capability to evaluate the clinical experience of a large number of individuals, yet there are unique methodological challenges involved in their use to evaluate cancer outcomes. To discuss methodological challenges and potential solutions, the Food and Drug Administration and the National Cancer Institute convened a two-day public meeting in 2014. This commentary summarizes the most salient issues discussed at the meeting. Published by Elsevier Inc.

  3. 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.

  4. Diagnostic evaluation and risk factors for drug allergies in children: from clinical history to skin and challenge tests.

    Science.gov (United States)

    Arikoglu, Tugba; Aslan, Gulen; Batmaz, Sehra Birgul; Eskandari, Gulcin; Helvaci, Ilter; Kuyucu, Semanur

    2015-08-01

    Parent or self-reported drug allergy claims frequently overestimate the real incidence of hypersensitivity reactions. A detailed and algorithmic diagnostic evaluation of drug reactions may allow a proper diagnosis. The aim of this study was to determine the confirmation rates and risk factors for confirmed allergic drug reactions in children. Mersin University Hospital in Turkey. The study consisted of children between ages of 8 months and 18 years with the history of suspected drug allergy as reported by the clinician or the patients. Parents were interviewed by a clinician to complete questionnaires that included questions about demographic data and characteristics of index drug reaction. Immediate reactions (IRs) were assessed with immediate-reading skin prick (SPT) and intradermal tests (IDT). Nonimmediate reactions (NIRs) were assessed with SPT, both early and delayed reading of IDT and patch tests. In case of negative skin tests, drug provocation tests were performed. The possible risk factors for confirmed drug allergy in univariate analysis (p Parent or self-reported drug allergy should be evaluated with a standardized diagnostic work-up before strict prohibitions are made. In addition, family and personal histories of drug allergy were significant risk factors related to allergic drug reactions in children.

  5. 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…

  6. Evaluation of a New Molecular Entity as a Victim of Metabolic Drug-Drug Interactions-an Industry Perspective.

    Science.gov (United States)

    Bohnert, Tonika; Patel, Aarti; Templeton, Ian; Chen, Yuan; Lu, Chuang; Lai, George; Leung, Louis; Tse, Susanna; Einolf, Heidi J; Wang, Ying-Hong; Sinz, Michael; Stearns, Ralph; Walsky, Robert; Geng, Wanping; Sudsakorn, Sirimas; Moore, David; He, Ling; Wahlstrom, Jan; Keirns, Jim; Narayanan, Rangaraj; Lang, Dieter; Yang, Xiaoqing

    2016-08-01

    Under the guidance of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), scientists from 20 pharmaceutical companies formed a Victim Drug-Drug Interactions Working Group. This working group has conducted a review of the literature and the practices of each company on the approaches to clearance pathway identification (fCL), estimation of fractional contribution of metabolizing enzyme toward metabolism (fm), along with modeling and simulation-aided strategy in predicting the victim drug-drug interaction (DDI) liability due to modulation of drug metabolizing enzymes. Presented in this perspective are the recommendations from this working group on: 1) strategic and experimental approaches to identify fCL and fm, 2) whether those assessments may be quantitative for certain enzymes (e.g., cytochrome P450, P450, and limited uridine diphosphoglucuronosyltransferase, UGT enzymes) or qualitative (for most of other drug metabolism enzymes), and the impact due to the lack of quantitative information on the latter. Multiple decision trees are presented with stepwise approaches to identify specific enzymes that are involved in the metabolism of a given drug and to aid the prediction and risk assessment of drug as a victim in DDI. Modeling and simulation approaches are also discussed to better predict DDI risk in humans. Variability and parameter sensitivity analysis were emphasized when applying modeling and simulation to capture the differences within the population used and to characterize the parameters that have the most influence on the prediction outcome. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  7. STATISTICAL EVALUATION OF FITTING ACCURACY OF GLOBAL AND LOCAL DIGITAL ELEVATION MODELS IN IRAN

    Directory of Open Access Journals (Sweden)

    F. Alidoost

    2013-09-01

    Full Text Available Digital Elevation Models (DEMs are one of the most important data for various applications such as hydrological studies, topography mapping and ortho image generation. There are well-known DEMs of the whole world that represent the terrain's surface at variable resolution and they are also freely available for 99% of the globe. However, it is necessary to assess the quality of the global DEMs for the regional scale applications.These models are evaluated by differencing with other reference DEMs or ground control points (GCPs in order to estimate the quality and accuracy parameters over different land cover types. In this paper, a comparison of ASTER GDEM ver2, SRTM DEM with more than 800 reference GCPs and also with a local elevation model over the area of Iran is presented. This study investigates DEM’s characteristics such as systematic error (bias, vertical accuracy and outliers for DEMs using both the usual (Mean error, Root Mean Square Error, Standard Deviation and the robust (Median, Normalized Median Absolute Deviation, Sample Quantiles descriptors. Also, the visual assessment tools are used to illustrate the quality of DEMs, such as normalized histograms and Q-Q plots. The results of the study confirmed that there is a negative elevation bias of approximately 5 meters of GDEM ver2. The measured RMSE and NMAD for elevation differences of GDEM-GCPs are 7.1 m and 3.2 m, respectively, while these values for SRTM and GCPs are 9.0 m and 4.4 m. On the other hand, in comparison with the local DEM, GDEM ver2 exhibits the RMSE of about 6.7 m, a little higher than the RMSE of SRTM (5.1 m.The results of height difference classification and other statistical analysis of GDEM ver2-local DEM and SRTM-local DEM reveal that SRTM is slightly more accurate than GDEM ver2. Accordingly, SRTM has no noticeable bias and shift from Local DEM and they have more consistency to each other, while GDEM ver2 has always a negative bias.

  8. Development and evaluation of a test program for Y-site compatibility testing of total parenteral nutrition and intravenous drugs

    OpenAIRE

    Staven, Vigdis; Wang, Siri; Gr?nlie, Ingrid; Tho, Ingunn

    2016-01-01

    Background There is no standardized procedure or consensus to which tests should be performed to judge compatibility/incompatibility of intravenous drugs. The purpose of this study was to establish and evaluate a test program of methods suitable for detection of physical incompatibility in Y-site administration of total parenteral nutrition (TPN) and drugs. Methods Eight frequently used methods (dynam...

  9. Intelligence and High Intensity Drug Trafficking Areas (HIDTA’s): A Critical Evaluation of the HIDTA Investigative Support Center (ISC)

    Science.gov (United States)

    2004-09-01

    The purpose of this thesis is to evaluate critically the ongoing reform of the High Intensity Drug Trafficking Area (HIDTA) Investigative Support...or Fusion Center for information sharing between agencies investigating crimes relating to drug trafficking , terrorism, and money laundering.

  10. A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

    Science.gov (United States)

    Smithburger, Pamela L; Buckley, Mitchell S; Culver, Mark A; Sokol, Sarah; Lat, Ishaq; Handler, Steven M; Kirisci, Levent; Kane-Gill, Sandra L

    2015-08-01

    Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. Multicenter, observational study : Medical ICUs at three academic medical centers. Adult patients (age ≥ 18 yr old) receiving medication therapy. All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication

  11. 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.

  12. Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, local anesthetics, volume substitutes and medications used in general anesthesia.

    Science.gov (United States)

    Jurakić Toncić, Ruzica; Marinović, Branka; Lipozencić, Jasna

    2009-01-01

    Urticaria and angioedema are common allergic manifestations and medications are one of common triggering factors. The most severe immediate drug reaction is anaphylaxis. Apart from the well established IgE-mediated immediate type hypersensitivity reactions, the pathogenesis of drug-induced urticaria, angioedema and anaphylaxis often remains obscure. In this article, emphasis is put on nonallergic reactions to the most commonly used drug groups of nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, volume expanders and drugs used in general anesthesia. Urticaria is the second most common drug eruption after maculopapular exanthema. The mechanisms of acute urticarial reactions are multiple, mostly IgE mediated, but some drugs can induce immune complex reactions and activate complement cascade, while others can induce direct activation of mast cells and degranulation or activation of complement by non-immune mechanisms. With different types of medications different pathomechanisms are involved. Non-steroid anti-inflammatory drugs are thought to cause reaction due to cyclooxygenase-1 inhibition and overproduction of leukotrienes, blamed for cutaneous and respiratory symptoms. Angiotensin-converting enzyme inhibitors can cause fatal angioedema, which is partially explained with bradykinin excess and impairment of aminopeptidase P and dipeptidyl peptidase IV that are involved in the metabolism of substance P and bradykinin. It remains unknown what additional mechanisms are involved. Radiocontrast media and local anesthetics mostly cause nonallergic hypersensitivity reaction, but in rare cases true allergic reaction can occur. Dextran is known to cause IgG mediated, immune complex anaphylaxis and it is recommended to use human serum albumin as the safest colloid.

  13. Drug Utilization Evaluation of Vancomycin in a Referral Infectious Center in Mazandaran Province

    Directory of Open Access Journals (Sweden)

    Ebrahim Salehifar

    2015-10-01

    Full Text Available Background: DUE (Drug Utilization Evaluation studies can help identify and correct problems associated with irrational use of drugs. Considering lack of data regarding how rational vancomycin is being used, we evaluated this DUE study in a referral infectious center to evaluate compliance with guidelines in terms of rational use of this valuable antibiotic.Methods: This retrospective study was done for 6 months from March to September 2012 at Razi hospital, an educational hospital affiliated to Mazandaran University of Medical Sciences. Data including patients’ demographics, vancomycin dose, kidney function assessment, dose adjustments, sampling and culture were collected. Based on the HICPAC (Hospital Infection Control Practices Advisory Committee and Up-to-date 2012 advices, the concordance of practice with standard guidelines was assessed.Results: One hundred and forty six medical records were reviewed in this study. Fever and shortness of breath were the most common symptoms at the time of initiation of vancomycin. Skin infections, lower respiratory tract infection and septicemia were the most common initial diagnosis of patients. Sampling was done in almost one-third of patients. Most of patient with a specific order were received vancomycin in half an hour. Considering the indication, Vancomycin was administered appropriately in 58 percent of patients.Conclusion: Vancomycin was used irrationally in a great proportion of patients. The main observed drawbacks were empiric use of vancomycin without subsequent adjustment of antimicrobial agent according to culture and sensitivity data and lack of paying enough attention to calculation of creatinine clearance and dosage adjustment.

  14. 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.

  15. In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.

    Science.gov (United States)

    Bani-Jaber, Ahmad; Alshawabkeh, Iyad; Abdullah, Samaa; Hamdan, Imad; Ardakani, Adel; Habash, Maha

    2017-07-01

    Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

  16. An evaluation of a surgical telepresence system for an intrahospital local area network.

    Science.gov (United States)

    Schneider, A; Wilhelm, D; Bohn, U; Wichert, A; Feussner, H

    2005-01-01

    We evaluated a digital telepresence system in an operating theatre (OR) environment which enabled a consultant to join the surgical team from a remote site by audiovisual communication. The system is based on video transmission using a streaming technique, with a server and a client connected via a local area network (LAN). Two cameras can be remotely controlled: one camera is built into the OR lamp and a second, laparoscopic camera is mounted on a robotic arm. Another feature of the system is teledemonstration, which permits the remote consultant to demonstrate points of particular interest. We evaluated the system clinically in 237 cases. In 28 cases (12%), telepresence could not be established for various reasons, mainly human failure. In 42 cases (18%), the full potential of telepresence was used. Technical evaluation showed that a data rate of 2 Mbit/s provides sufficient audio and video quality, as well as reliable teledemonstration. The data transmission delay was acceptable for clinical purposes (video 0.92 s, audio 0.6 s from OR to client, audio 0.7 s from client to OR). The study showed that telepresence is a promising means of providing highly specialized expertise within the OR.

  17. Multicenter evaluation of the nitrate reductase assay for drug resistance detection of Mycobacterium tuberculosis.

    Science.gov (United States)

    Martin, Anandi; Montoro, Ernesto; Lemus, Dihadenys; Simboli, Norberto; Morcillo, Nora; Velasco, Maritza; Chauca, José; Barrera, Lucía; Ritacco, Viviana; Portaels, Françoise; Palomino, Juan Carlos

    2005-11-01

    The performance of the nitrate reductase assay was evaluated in a multicenter laboratory study to detect resistance of Mycobacterium tuberculosis to the first-line anti-tuberculosis drugs rifampicin, isoniazid, ethambutol and streptomycin using a set of coded isolates. Compared with the gold standard proportion method on Löwenstein-Jensen medium, the assay was highly accurate in detecting resistance to rifampicin, isoniazid and ethambutol with an accuracy of 98%, 96.6% and 97.9%, respectively. For streptomycin, discrepant results were obtained with an overall accuracy of 85.3%. The assay proved easy to be implemented in countries with limited laboratory facilities.

  18. Local adaptation and evaluation of a falls risk prevention approach in acute hospitals.

    Science.gov (United States)

    Walsh, Willeke; Hill, Keith D; Bennell, Kim; Vu, Michelle; Haines, Terry P

    2011-04-01

    To determine whether locally adapting a falls risk factor assessment tool results in an instrument with clinimetric properties sufficient to support an acute hospital's falls prevention program. Prospective cohort study of predictive validity and observational investigation of intra- and inter-rater reliability. Acute wards in two large hospitals in Melbourne, Australia. One hundred and thirty acute hospital inpatients participated in the predictive accuracy evaluation, with 25 and 35 inpatients used for the intra-rater and inter-rater reliability analyses, respectively. To develop a falls risk screen and assessment instrument through local adaptation of an existing tool. Clinimetric property analysis of new instrument (Western Health Falls Risk Assessment, WHeFRA) and comparison with 'gold standard tool' (STRATIFY). Fallers, falls and falls per 1000 bed days. Sensitivity (Sens), specificity (Spec), Youden Index (YI) and these three statistics based on event rate of falls (Sens(ER), Spec(ER) and YI(ER)), were calculated to determine predictive accuracy. Reliability was determined using intraclass correlation coefficient (ICC), weighted kappa and signed rank test. Seven participants (5.4%) fell, with 14 falls (fall rate: 10.7 falls per 1000 patient bed days). The WHeFRA instrument was significantly more accurate at predicting fallers and the rate of falls than the STRATIFY. Intra-rater reliability ICC (95% confidence intervals) for WHeFRA screen was 0.94 (0.86-0.97) and inter-rater reliability was 0.78 (0.61-0.88). Local adaptation of an existing tool resulted in an instrument with favorable clinimetric properties and may be a viable procedure for facilitating falls prevention program development and implementation in acute hospital settings.

  19. 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.

  20. Evaluation of a Novel Herbal Immunomodulator Drug (IMOD) in Treatment of Experimental Canine Visceral leishmaniasis.

    Science.gov (United States)

    Malmasi, Abdolali; Ziaie Ardestani, Bijan; Mohebali, Mehdi; Akhoundi, Behnaz; Ziaie, Shadi; Masoudifard, Majid; Khorram Khorshid, Hamidreza; Nasiri, Mehdi; Bayanolhagh, Saeed; Mostafavi, Ehsan; Delrobai, Moin; Siavashi, Vahid

    2014-01-01

    Toxicity and drug resistance against pentavalent antimonials, medications of choice in treatment of leishmaniasis for more than 5 decades, have become important subjects globally. This study was a randomized, open labeled trial that was designed to determine efficacy and safety of IMOD as a novel herbal immunomodulator drug for treatment of canine visceral leishmaniasis (CVL). Twenty healthy mongrel dogs were infected with Iranian strain of L. Infantum amastigotes and randomly divided to 5 groups with four animals for each included on: I: negative control (non-infected) II: Glucantime® III: Glucantime® plus IMOD (immune-chemotherapy) IV: IMOD and V: positive control (non-treated). Physical examination, hematological, biochemical, serological, parasitological, pathological and imaging evaluations were performed pre-/post- interventions every month for 3 months. Comparing with control groups (I&V), immune-chemotherapy group (Glucantime® plus IMOD) showed significantly higher efficacy in resolving the clinical signs and hematobiochemistry factors. Based on our results, using IMOD in combination with meglumine antimoniate (Glucantime®) has significantly improved CVL than the latter drug alone. So, it seems this new herbal medicine is useful as adjuvant therapy for canine visceral leishmaniasis.

  1. Evaluation of immunomodulatory effect of Ranahamsa Rasayanaya - A Sri Lankan classical rasayana drug, on experimental animals.

    Science.gov (United States)

    Somarathna, K Indrajith; Chandola, H M; Ravishankar, B; Pandya, K N; Attanayake, A M P; Ashok, B K

    2010-10-01

    Immunity plays a key role in maintaining the health of an individual. Therefore, the rational modulation of the immunity through psycho-neuro-endocrine-immune (PNI) axis is useful for the prevention as well as for the curing of the diseases. As immunomodulation is a parameter for evaluation of the rasayana effect of a drug, the same has been studied to assess the rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as antibody formation against sheep red blood cells (SRBC) and cell mediated immunity (CMI) have been carried out befitting on Wistar strain albino rats to determine the immunomodulatory effect plus rasayana effect of RR. Statistically significant increase in body weight, nonsignificant increase in antibody formation against SRBC, highly significant decrease in CMI were observed in the treatment groups, when compared to the standard control group. These results show the probable immunomodulatory and anabolic activities of the test drug. Outcome of these studies validate the strong rasayana effect of the test drug claimed by the traditional practitioners of Sri Lanka.

  2. Preparation and in vitro evaluation of mebeverine HCl colon-targeted drug delivery system.

    Science.gov (United States)

    Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Chitneni, Mallikarjun; Mutee, Ahmed F; Ameer, Omar Z; Salman, Ibrahim M; Noor, Azmin M

    2011-08-01

    Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon.

  3. Blood-Vessel-on-a-Chip Platforms for Evaluating Nanoparticle Drug Delivery Systems.

    Science.gov (United States)

    Li, Yuancheng; Zhu, Kai; Liu, Xiao; Zhang, Y Shrike

    2017-09-24

    Nanoparticle-based drug delivery systems hold great promise for the treatment of major diseases. However, their slow translation from bench to the clinic posts a serious concern. It is mainly attributed to the lack of suitable in vitro platforms for rapid and accurate screening of nanomedicine. Recent developments in microfluidic technologies have provided the possibility to reproduce the biomimetic blood vessel microenvironments outside the body, thus offering a convenient means to characterize the in vivo dynamics and biological responses of nanoparticles. In this review, we discuss the challenges facing the field of nanoparticle drug delivery and highlight the urgent need for construction of blood-vessel-on-a-chip platforms for testing nanomedicine. We subsequently illustrate advances in fabricating various well-controlled blood-vessel-on-a-chip platforms, covering a few examples that have used such models for evaluating nanoparticles behaviors. We then summarize with conclusions and perspectives. We anticipate that, further development of these blood-vessel-on-a-chip platforms with improved biomimetic parameters, tissue specificity, and personalization, will enable their wide applications in drug screening including nanomedicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. 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.

  5. New Indicators to Compare and Evaluate Harmful Drug Use Among Adolescents in 38 European Countries

    Directory of Open Access Journals (Sweden)

    Mammone Alessia

    2014-10-01

    Full Text Available AIMS – New trends in drug consumption reveal increasing polydrug use. Epidemiological indicators in the current use are based on the prevalence and the associated potential harm of a single “main” substance. We propose new indicators to evaluate frequency and potential harm of poly-drug use. The indicators are used to compare drug use among countries based on survey data on adolescents’ substance use in 38 European countries. METHODS – The approach is based on analysis of the frequency of use in the various population samples: lifetime use, twelve months use or last thirty days, depending on available data, and on the risk of harm for the substances used. Two indicators are provided: the frequency of use score (FUS by summing the frequency of use of each substance, and the polydrug use score (PDS that weight all the substances used by their risk. RESULTS – The indicators FUS and PDS were calculated and the distribution functions were used to characterise substance use across ESPAD countries. The analysis shows important differences in poly-substance use severity among countries presenting similar prevention policies. CONCLUSIONS – Systematic analysis of substance use and the related risk are of paramount interest. The proposed indicators are designed to better monitor and understand consequences of polydrug use and to measure the resulting risk at country or population level. The indicators may also be used to assess the effects of policy interventions.

  6. Mid-Term Assessment of the EU Drugs Strategy 2013–2020 and Final Evaluation of the Action Plan on Drugs 2013–2016

    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

    Abstract 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.

  7. Data evaluation and CNGS beam localization with the precision tracker of the OPERA detector

    Energy Technology Data Exchange (ETDEWEB)

    Bick, D.

    2007-04-15

    In this diploma thesis, the data evaluation for the OPERA precision tracker is presented. Furthermore investigations of a precise CNGS beam localization with the precision tracker are performed. After an overview of past and present developments in neutrino physics, the OPERA detector is presented in this thesis. Emphasis is given to the precision tracker which has been partly commissioned in the end of the last year. A first analysis of the functionality with cosmic muons has been performed, as well as the inclusion of data in the OPERA software framework. Within this thesis some useful tools have been developed which are also presented. Finally, divergence effects from the nominal beam line of the CNGS neutrino beam and possible detection with the precision tracker are studied. (orig.)

  8. 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

    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 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. Conclusion The

  9. A systematic review of observational studies evaluating costs of adverse drug reactions

    Directory of Open Access Journals (Sweden)

    Batel Marques F

    2016-08-01

    Full Text Available Francisco Batel Marques,1,2 Ana Penedones,1,2 Diogo Mendes,1,2 Carlos Alves,1,2 1CHAD – Centre for Health Technology Assessment and Drug Research, AIBILI – Association for Innovation and Biomedical Research on Light and Image, 2School of Pharmacy, University of Coimbra, Coimbra, Portugal Introduction: The growing evidence of the increased frequency and severity of adverse drug events (ADEs, besides the negative impact on patient’s health status, indicates that costs due to ADEs may be steadily rising. Observational studies are an important tool in pharmacovigilance. Despite these studies being more susceptible to bias than experimental designs, they are more competent in assessing ADEs and their associated costs.Objective: To identify and characterize the best available evidence on ADE-associated costs.Methods: MEDLINE, Cochrane Library, and Embase were searched from 1995 to 2015. Observational studies were included. The methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies. Studies were classified according to the setting analyzed in “ambulatory”, “hospital”, or both. Costs were classified as “direct” and “indirect”. Data were analyzed using descriptive statistics. The total incremental cost per patient with ADE was estimated.Results: Twenty-nine (94% longitudinal observational studies and two (7% cross-sectional studies were included. Twenty-three (74% studies were assessed with the highest methodological quality score. The studies were mainly conducted in the US (61%. Twenty (65% studies evaluated any therapeutic group. Twenty (65% studies estimated costs of ADEs leading to or prolonging hospitalization. The “direct costs” were evaluated in all studies, whereas only two (7% also estimated the “indirect costs”. The “direct costs” in ambulatory ranged from €702.21 to €40,273.08, and the in hospital from €943.40 to €7

  10. Creating the first MedlinePlus "Go Local" service: lessons and recommendations from the evaluation of NC Health Info.

    Science.gov (United States)

    Silbajoris, Christie; McDuffee, Diana; Olney, Cynthia

    2007-01-01

    NC Health Info is an online collection of North Carolina based health services Web sites that seamlessly links local health resources to topical health information on MedlinePlus, the National Library of Medicine's consumer health information Web site. NC Health Info was the first project to connect local resources with MedlinePlus in the "Go Local" initiative. As such, NC Health Info serves as a model for other states to follow in connecting their own local information with Medline- Plus. This paper describes the processes used and lessons learned during a year-long evaluation of NC Health Info. Evaluation results may be of interest and applicable to any existing or planned "Go Local" project.

  11. In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.

    Science.gov (United States)

    Ikeda, Kenji; Utoguchi, Naoki; Tsutsui, Hidenobu; Yamaue, Satoko; Homemoto, Manami; Nakao, Erina; Hukunaga, Yumi; Yamasaki, Kyohei; Myotoku, Michiaki; Hirotani, Yoshihiko

    2011-02-01

    Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  12. Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults.

    Science.gov (United States)

    Chmielewska, B; Stelmasiak, Z

    2001-01-01

    Second generation antiepileptics lamotrigine (LTG) and tiagabine (TGB) were primarily licensed for adjunctive treatment of simple and complex partial seizures with/without secondary generalisation as similarly effective drugs. Reduction of seizures frequency is the most important index of drug efficacy, but overall therapeutic benefit estimated as a quality of life is nowadays the target goal of management. In this study efficacy and tolerability of LTG or TGB as short-term add-on treatment in patients with refractory complex partial seizures were assessed by the use of both physician-rated measures (mean monthly seizure frequency, responders rate, adverse events, clinical biochemistry) and patients perceived change in their own quality of life estimation (descriptive scale and visual analogue scale-VAS). Comparable efficacy of LTG (n-22, 378 mg/day) and TGB (n-26, 43 mg/g) was assessed as 41 and 35% of responders and above half of patients with noticeable improvement. 25% of patients in both groups reported reduction of seizures severity in 4-points descriptive scale. Biochemistry values did not show clinically significant changes after treatment. 13% of patients on LTG reported adverse events (headache, asthenia, irritability, insomnia). This coefficient was greater for TGB-35% (asthenia, headache, sleepiness, vertigo). However, no case of discontinuation as a result of adverse events was reported for either of the tested drugs. Even if efficacy of LTG and TGB was comparable in objective measurements, only patients on LTG reported a significant quality of life improvement in VAS. This might be the consequence of more frequent adverse events and treatment schedule of TGB (triple dosing/day). This trial confirmed that VAS might be used as an easy additional test in evaluation of antiepileptic drug for individual patient in everyday clinical practice.

  13. Performance Evaluation of Multichannel Adaptive Algorithms for Local Active Noise Control

    Science.gov (United States)

    DE DIEGO, M.; GONZALEZ, A.

    2001-07-01

    environments and at frequencies below 230 Hz are presented. Better noise levels attenuation is obtained in the semianechoic chamber due to the simplicity of the acoustic field. The size of the zone of quiet makes the system useful at relatively low frequencies and it is large enough to cover a listener's head movements. The spatial extent of the zones of quiet is generally observed to increase as the error sensors are moved away from the secondary source, they are put closer together or its number increases. In summary, different algorithms' performance and the viability of the multichannel system for local active noise control in real listening conditions are evaluated and some guidelines for designing such systems are then proposed.

  14. Evaluation of the effects of health impact assessment practice at the local level in Monteregie.

    Science.gov (United States)

    Nour, Kareen; Dutilly-Simard, Sarah; Brousselle, Astrid; Smits, Pernelle; Buregeya, Jean-Marie; Loslier, Julie; Denis, Jean-Louis

    2016-01-27

    In Quebec (Canada), the Monteregie Regional Public Health Department has chosen to use health impact assessment (HIA) to support municipalities through a knowledge exchange and collaborative process in order to positively influence decision-making regarding local policies and projects. The value of HIA is becoming increasingly recognized by municipalities interested in planning and managing their cities with an eco-systemic perspective. However, the knowledge and tools which support the use of the HIA at regional and local levels are still missing. The general objective is to evaluate the impact the collaborative HIA process used in Monteregie has had on the formulation, adoption and implementation of policies and projects favourable to health. The methodology is based on Mayne's CA design, which allows the identification of factors which contribute to a change process. It is described as one of the best approaches to reduce uncertainty regarding the observed results and the contribution of a program. All of the HIA processes realised between January 2013 and January 2016 in Monteregie will be studied following a case study strategy. Study populations include regional and local public health professionals, municipal officers and community members implicated in these HIAs. Various qualitative and quantitative methods will be used, including examination of documentation, observations on the city grounds, and individual or group interviews. A model of change will be constructed for each HIA process and will present the logical pathway which leads to the observed results, alternative explanations and hypothesises as to why these results were obtained, and contextual factors that could have influenced them. This model will allow the production of a refined contribution story for each HIA. A convergence and divergence analysis will be completed in order to identify differences or similitudes between the different HIAs studied. In addition to contributing to the

  15. PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery: Characterization and in-situ hyperspectral fluorescence and 2-photon localization.

    Science.gov (United States)

    Lunardi, Claure N; Gomes, Anderson J; Palepu, Sandeep; Galwaduge, P Thilanka; Hillman, Elizabeth M C

    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 5070nm 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  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 impact of Federal Alcohol and Drug Abuse block grants on state and local government substance abuse program expenditures: the role of federal oversight.

    Science.gov (United States)

    Gamkhar, S; Sim, S C

    2001-12-01

    Are the federal Alcohol and Drug Abuse (ADA) block grant funds substituting for or supplementing state and local government spending on substance abuse? Using panel data on state and local government substance abuse programs, this study explores the fiscal effects of the ADA block grant money and the increased enforcement (after 1989) of federal restrictions on state spending of ADA block grants. The findings here reveal that for the current period, the federal ADA grant has no statistically significant effect on state and local government substance abuse spending both before and after 1989, and the increased enforcement of federal restrictions on the ADA grants after 1989 does not change this result. An additional finding is that lagged ADA grants have had a large effect on substance abuse spending both before and after 1989--a feature of the program not considered in previous studies.

  18. Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Luana da S. M. Forezi

    2014-05-01

    Full Text Available As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

  19. Preclinical quantitative MicroPET imaging in evaluation of neuroprotective drug candidates

    Energy Technology Data Exchange (ETDEWEB)

    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 [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    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. [{sup 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 [{sup 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) [{sup 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.

  20. Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits.

    Science.gov (United States)

    Fallon, Erica M; Nehra, Deepika; Carlson, Sarah J; Brown, David W; Nedder, Arthur P; Rueda, Bo R; Puder, Mark

    2014-03-01

    Sunitinib (Sutent) is a Food and Drug Administration-approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits. Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated. All animals survived until designated euthanasia. There was no evidence of intra-abdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal. These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. Process evaluation of an environmental and educational nutrition intervention in residential drug-treatment facilities.

    Science.gov (United States)

    Cowan, Jennifer A; Devine, Carol M

    2012-07-01

    To evaluate the implementation of a controlled, 6-week, environmental and educational intervention to improve dietary intake and body composition, and to study the association of implementation fidelity with diet and body composition outcomes. A process evaluation documented participation, dose of nutrition education delivered, participant satisfaction, fidelity and completeness of the food environment intervention implementation, and context through observations and interviews with staff and residents. Intervention sites were scored and categorized as high or low participation and implementation and compared on essential elements of the food environment and on diet and body composition outcomes. Six urban residential drug-treatment facilities in Upstate New York. Fifty-five primarily black and white men in residential drug-treatment programmes. Participants were exposed to 94 % and 69 % of the educational and environmental elements, respectively. High implementation sites were significantly more likely to provide water and 100 % juice, offer fruit or vegetable salad, offer choices of fruits and vegetables, and limit fried foods. Mixed-model analysis of covariance revealed that participants in the high participation and implementation sites reported greater reductions in total energy, percentage of energy from sweets, daily servings of fats, oils and sweets, and BMI over the intervention period. Participants in low participation and implementation sites reported greater reductions in percentage of energy from fat. Differential implementation of environmental elements limited the intervention impact. These findings document the contribution of changes in eating environments to facilitate dietary behaviour change in community residential substance-abuse settings.

  3. Formulation and evaluation of anti-asthmatic drug montelukast in mucoadhesive buccal patches

    Directory of Open Access Journals (Sweden)

    Magdy Ibrahim Mohamed

    2014-11-01

    Full Text Available Objective: To formulate and evaluate anti-asthmatic drug montelukast in mucoadhesive buccal patches. Methods: Buccal patches were formulated by using different hydrophilic polymers by solvent casting technique. Buccal patches were evaluated by seven physical appearances, in addition to in vitro drug release study. Results: All patches were uniform and translucent, and had smooth surface. In vitro release studies were conducted for montelukast buccal patches proved that release in the range of 75.26%-92.30% in 8 h. Emission of montelukast from all patches simulated zero order and diffusion mechanism. Finally it can be concluded that F3, F15 and F16 are the best formulation. Conclusions: The investigation concluded that patch of 5 mg of montelukast sodium were formulated by using sodium alginate with sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose K100M with sodium carboxy methyl cellulose, and hydroxy propyl methyl cellulose K100M with sodium alginate (F3, F15 and F16 formulations were the best formulations.

  4. 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.

  5. Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol.

    Science.gov (United States)

    Rowland, Angela; van Dyk, Madelé; Warncken, David; Mangoni, Arduino A; Sorich, Michael J; Rowland, Andrew

    2017-11-26

    To evaluate the capacity for modafinil to be a perpetrator of metabolic drug-drug interactions by altering cytochrome P450 activity following a single dose and dosing to steady state. A single centre, open label, single sequence cocktail drug interaction trial. On days 0, 2 and 8 participants were administered an oral drug cocktail comprising 100 mg caffeine, 30 mg dextromethorphan, 25 mg losartan, 1 mg midazolam and 20 mg enteric-coated omeprazole. Timed blood samples were collected prior to and for up to 6 h post cocktail dosing. Between days 2 and 8 participants orally self-administered 200 mg modafinil each morning. Following a single 200 mg dose of modafinil mean (± 95% CI) AUC ratios for caffeine, dextromethorphan, losartan, midazolam and omeprazole were 0.95 (± 0.08), 1.01 (± 0.35), 0.97 (± 0.10), 0.98 (± 0.10) and 1.36 (± 0.06), respectively. Following dosing of modafinil to steady state (200 mg for 7 days), AUC ratios for caffeine, dextromethorphan, losartan, midazolam and omeprazole were 0.90 (± 0.16), 0.79 (± 0.09), 0.98 (± 0.11), 0.66 (± 0.12) and 1.90 (± 0.53), respectively. These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways. © 2017 The British Pharmacological Society.

  6. 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

  7. Educational Interventions and Evaluation for Obesity Prevention in Preschool Children in Local Communities.

    Science.gov (United States)

    Yoshiike, Nobuo; Iwabe, Maiko; Yoshioka, Yoshiko

    2017-01-01

    Educational interventions for obesity prevention from early childhood is one of the important measures in health promotion policies, especially in locations where obesity and overweight in school and preschool children are prevalent, such as in the Aomori Prefecture. The Aomori Prefecture government started a new demonstration project in FY 2014 that targeted children in nursing schools for the prevention of obesity through both population approaches (nutrition/physical activity education and nutrition management in lunch programs) and individual approaches to solving overweight in children. Our study group developed a data management tool to routinely accumulate data on measured body height and weight. We also developed educational materials with growth charts for nutritional education of guardians, and summary sheets showing the distributions of degree of obesity and prevalence of overweight/obesity in age-sex groups for use in assessment in each nursing school. To promote and evaluate the demonstration project, we offered the data management tool to all nursing schools in the prefecture for nutritional education and management in the nursing schools and asked them to anonymously submit data to build a prefecture-based monitoring dataset. Around 70% (310 institutes) of the institutes responded to this request, and we developed a longitudinal dataset with about 4,000 children in each of the 3-, 4-, and 5-year-old cohorts. This first revealed the prevalence of overweight in preschool children in the entire prefecture. The dataset will be further utilized for evaluating the effectiveness of educational interventions in preschool settings in local communities.

  8. Evaluation of Tropospheric and Ionospheric Effects on the Geographic Localization of Data Collection Platforms

    Directory of Open Access Journals (Sweden)

    C. C. Celestino

    2007-01-01

    Full Text Available The Brazilian National Institute for Space Research (INPE is operating the Brazilian Environmental Data Collection System that currently amounts to a user community of around 100 organizations and more than 700 data collection platforms installed in Brazil. This system uses the SCD-1, SCD-2, and CBERS-2 low Earth orbit satellites to accomplish the data collection services. The main system applications are hydrology, meteorology, oceanography, water quality, and others. One of the functionalities offered by this system is the geographic localization of the data collection platforms by using Doppler shifts and a batch estimator based on least-squares technique. There is a growing demand to improve the quality of the geographical location of data collection platforms for animal tracking. This work presents an evaluation of the ionospheric and tropospheric effects on the Brazilian Environmental Data Collection System transmitter geographic location. Some models of the ionosphere and troposphere are presented to simulate their impacts and to evaluate performance of the platform location algorithm. The results of the Doppler shift measurements, using the SCD-2 satellite and the data collection platform (DCP located in Cuiabá town, are presented and discussed.

  9. 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.

  10. Implementation and evaluation of a multisite drug usage evaluation program across Australian hospitals - a quality improvement initiative.

    Science.gov (United States)

    Pulver, Lisa K; Wai, Angela; Maxwell, David J; Robertson, Marion B; Riddell, Steven

    2011-08-29

    With the use of medicines being a broad and extensive part of health management, mechanisms to ensure quality use of medicines are essential. Drug usage evaluation (DUE) is an evidence-based quality improvement methodology, designed to improve the quality, safety and cost-effectiveness of drug use. The purpose of this paper is to describe a national DUE methodology used to improve health care delivery across the continuum through multi-faceted intervention involving audit and feedback, academic detailing and system change, and a qualitative assessment of the methodology, as illustrated by the Acute Postoperative Pain Management (APOP) project. An established methodology, consisting of a baseline audit of inpatient medical records, structured patient interviews and general practitioner surveys, followed by an educational intervention and follow-up audit, is used. Australian hospitals, including private, public, metropolitan and regional, are invited to participate on a voluntary basis. De-identified data collected by hospitals are collated and evaluated nationally to provide descriptive comparative analyses. Hospitals benchmark their practices against state and national results to facilitate change. The educational intervention consists of academic detailing, group education, audit and feedback, point-of-prescribing prompts and system changes. A repeat data collection is undertaken to assess changes in practice.An online qualitative survey was undertaken to evaluate the APOP program. Qualitative assessment of hospitals' perceptions of the effectiveness of the overall DUE methodology and changes in procedure/prescribing/policy/clinical practice which resulted from participation were elicited. 62 hospitals participated in the APOP project. Among 23 respondents to the evaluation survey, 18 (78%) reported improvements in the documentation of pain scores at their hospital. 15 (65%) strongly agreed or agreed that participation in APOP directly resulted in increased

  11. 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.

  12. 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.

  13. Utilization Evaluation of Antimicrobial Agents in Neutropenic Cancer Patients in a Teaching hospital: Urgent of Drug Utilization Evaluation Studies

    Directory of Open Access Journals (Sweden)

    Hadi Hamishehkar

    2015-10-01

    Full Text Available Background: More than 80% of patients with hematologic malignancies will develop fever during more than one chemotherapy cycle combined with neutropenia. We aim to evaluate empiric antibiotic strategies in Febrile Neutropenic (FN cancer patients.Methods: This is a concurrent study performed in the “Shahid Ghazi” teaching hospital, hematology-oncology center of Tabriz, Iran during the period of December 2011 to September2012. During this period, patients with FN were evaluated in view of antibiotics utilization based on Infectious Disease Society of America (IDSA and National Comprehensive Cancer Network (NCCN instructions.Results: Seventy patients had a total of 91 episodes of FN in the duration of this study. Among them 63 (90% patients were the cases of acute leukemia. For 88 (96.7 % patients, imipenem was used as the initial empirical antibiotic regimen. It was changed to piperacillin/tazobactam in 8 (8.8% of them without indication. Cultures didn’t obtain before the initiation of empirical therapy in 19 (20.9% episodes. Empiric vancomycin didn’t discontinue after 3 days even if it was not warranted in 23 episodes. In 16 cases vancomycin was switched to teicoplanin. The fluconazole dosages generally given to patients were all suboptimal. Adjusting the dosages of vancomycin or imipenem was not done correctly in 13 (14.29% episodes.Conclusion: The results of this study showed that choosing antimicrobial agents and their dosing for prophylaxis and treatment of FN patients and discharge antimicrobial planning of FN patients do not follow the evaluated guidelines. Drug Usage Evaluation studies need to be done regularly in such a center.

  14. Health economic evaluation in complementary medicine: development within the last decades concerning local origin and quality.

    Science.gov (United States)

    Ostermann, Thomas; Krummenauer, Frank; Heusser, Peter; Boehm, Katja

    2011-12-01

    This evaluation investigates characteristics of health economics evaluations in CAM. Particular emphasis is paid to differences regarding continental origin and time of publication of investigations. Database searches to identify potential studies were carried out in Medline (via Pubmed), the Cochrane Central Register of Controlled Trials 1st Quarter 2010, the Cochrane Database of Systematic Reviews 2005 to January 2010, the Cochrane Methodology Register 1st Quarter 2010, the Database of Abstracts of Reviews of Effects 1st Quarter 2010, Health Technology Assessment (via OVID) and CAMbase. Data were screened, extracted and the methodological quality of the underlying publications was assessed. Univariate statistical analyses were carried out and Classification and Regression Tree (CART) analysis was performed. One hundred and forty-three studies were included in this review, 43 of which were randomised trials. Of all included studies 56% were carried out in primary care settings and 54% chose the perspective of health care provider/health insurance. When the study characteristics were stratified for the "year of publication" (before versus in/after 2002), locally significant differences were found for study setting (Chi-square p=0.014) and methodological quality (Mann/Whitney p=0.014). Furthermore, studies from America differed from those conducted in Europe with respect to the field of CAM (p<0.001, Chi-square). There were also differences in trial settings as the majority of European studies was carried out in primary care settings (n=54; 70%), whereas American studies had a broader scope with only 24 studies (42%) in the field of primary care. The CART analyses confirmed the findings of the univariate analysis. Differences in healthcare systems were mirrored by the observed differences in CAM related health economic evaluations. Basic requirements for reporting and conducting clinical trials ought to be met in more studies evaluating health economics. Such

  15. A tool to evaluate local biophysical effects on temperature due to land cover change transitions

    Science.gov (United States)

    Perugini, Lucia; Caporaso, Luca; Duveiller, Gregory; Cescatti, Alessandro; Abad-Viñas, Raul; Grassi, Giacomo; Quesada, Benjamin

    2017-04-01

    Land Cover Changes (LCC) affect local, regional and global climate through biophysical variations of the surface energy budget mediated by albedo, evapotranspiration, and roughness. Assessment of the full climate impacts of anthropogenic LCC are incomplete without considering biophysical effects, but the high level of uncertainties in quantifying their impacts to date have made it impractical to offer clear advice on which policy makers could act. To overcome this barrier, we provide a tool to evaluate the biophysical impact of a matrix of land cover transitions, following a tiered methodological approach similar to the one provided by the IPCC to estimate the biogeochemical effects, i.e. through three levels of methodological complexity, from Tier 1 (i.e. default method and factors) to Tier 3 (i.e. specific methods and factors). In particular, the tool provides guidance for quantitative assessment of changes in temperature following a land cover transition. The tool focuses on temperature for two main reasons (i) it is the main variable of interest for policy makers at local and regional level, and (ii) temperature is able to summarize the impact of radiative and non-radiative processes following LULCC. The potential changes in annual air temperature that can be expected from various land cover transitions are derived from a dedicated dataset constructed by the JRC in the framework of the LUC4C FP7 project. The inputs for the dataset are air temperature values derived from satellite Earth Observation data (MODIS) and land cover characterization from the ESA Climate Change Initiative product reclassified into their IPCC land use category equivalent. This data, originally at 0.05 degree of spatial resolution, is aggregated and analysed at regional level to provide guidance on the expected temperature impact following specific LCC transitions.

  16. An areomorphometric visualisation and evaluation tool for HRSC DTM-derived local slope histograms

    Science.gov (United States)

    Balint, Zita; Székely, Balázs; Kovács, Gábor; Jansa, Josef; Dorninger, Peter; Podobnikar, Tomaž

    2013-04-01

    In the last years morphometric study of Martian surface has become a primary research field. The various surface processes shape the Martian landforms creating a diverse spatial relief pattern. The diversity of the surface can be captured via the quantitative analysis of local slope angle histogram parameters. Several complete HRSC orbit DTMs have been converted to a series of local slope histograms calculated for 4x4 km spatial window, including the Nanedi Valles region. Our goal is to outline the different areomorphological units based on the statistical parameters of the slope distribution. To this end, a visualization program code was developed that allows to render the parameter maps like amplitude of the mode, skewness and standard deviation of the distribution as RGB-(red, green, blue)-coloured pixels, resulting in a colour image. In this image map the different colours represent very different types of slope histograms. The individual morphological types, regions (e.g., the valleys, in some cases, valley floors and valley sides, and crater rims) can be clearly distinguished from the surrounding plateau-like, low-relief areas. This approach is also applicable for the aforementioned individual channels (colours), because the spatial changes in some cases are also visible, certain parameters have characteristic spatial trends, e.g., in the case of skewness the sides of the vallis a remarkably apparent. The detailed evaluation of these image maps may help in automated classification of the areomorphometric domains. This is a contribution of the TMIS.ascrea project, financed by the Austrian Research Promotion Agency (FFG).

  17. Multiparametric-MRI as a comprehensive study in evaluation, characterization & local staging of urinary bladder carcinomas

    Directory of Open Access Journals (Sweden)

    Ahmed Hafez Afifi

    2017-06-01

    Conclusion: Mp-MRI is comprehensive & effective tool for determining local T stages, and the histological grades of urinary bladder cancers. Also, it predicts nature & stages of local lymph nodes, exhibiting high diagnostic performance with excellent objectivity.

  18. Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Rovira, I., E-mail: immamartinez@gmail.com; Prezado, Y. [Laboratoire d’Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Université Paris 7 and 11, Campus Universitaire, Bât. 440, 1er étage, 15 rue Georges Clemenceau, Orsay Cedex 91406 (France)

    2015-11-15

    Purpose: The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high-Z nanoparticles. Since 2004, spectacular results have been obtained when low-energy x-ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high-Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy. Methods: For this purpose, Monte Carlo calculations (GATE/GEANT4 code) were performed. In particular, the GEANT4-DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source-nanoparticle distances and source sizes). Results: This Monte Carlo study shows the influence of the simulations’ parameters on the local

  19. 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.

  20. Evaluation of clip localization for different kilovoltage imaging modalities as applied to partial breast irradiation setup

    Energy Technology Data Exchange (ETDEWEB)

    Buehler, Andreas; Ng, Sook-Kien; Lyatskaya, Yulia; Stsepankou, Dzmitry; Hesser, Jurgen; Zygmanski, Piotr [University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, D-68167 Mannheim (Germany); Department of Radiation Oncology and Brigham and Women' s Hospital, and Harvard Medical School, Boston, Massachusetts 02115 (United States); University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, D-68167 Mannheim (Germany); Department of Radiation Oncology and Brigham and Women' s Hospital, and Harvard Medical School, Boston, Massachusetts 02115 (United States)

    2009-03-15

    Surgical clip localization and image quality were evaluated for different types of kilovoltage cone beam imaging modalities as applied to partial breast irradiation (PBI) setup. These modalities included (i) clinically available radiographs and cone beam CT (CB-CT) and (ii) various alternative modalities based on partial/sparse/truncated CB-CT. An anthropomorphic torso-breast phantom with surgical clips was used for the imaging studies. The torso phantom had artificial lungs, and the attached breast phantom was a mammographic phantom with realistic shape and tissue inhomogeneities. Three types of clips of variable size were used in two orthogonal orientations to assess their in-/cross-plane characteristics for image-guided setup of the torso-breast phantom in supine position. All studies were performed with the Varian on-board imaging (OBI, Varian) system. CT reconstructions were calculated with the standard Feldkamp-Davis-Kress algorithm. First, the radiographs were studied for a wide range of viewing angles to characterize image quality for various types of body anatomy in the foreground/background of the clips. Next, image reconstruction quality was evaluated for partial/sparse/truncated CB-CT. Since these modalities led to reconstructions with strong artifacts due to insufficient input data, a knowledge-based CT reconstruction method was also tested. In this method, the input data to the reconstruction algorithm were modified by combining complementary data sets selected from the treatment and reference projections. Different partial/sparse/truncated CB-CT scan types were studied depending on the total arc angle, angular increment between the consequent views (CT projections), orientation of the arc center with respect to the imaged breast and chest wall, and imaging field size. The central angles of the viewing arcs were either tangential or orthogonal to the chest wall. Several offset positions of the phantom with respect to the reference position were