Science.gov

Sample records for drug shows positive

  1. Parkinson's Drug Shows Promise Against Macular Degeneration

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_155695.html Parkinson's Drug Shows Promise Against Macular Degeneration But more ... THURSDAY, Nov. 12, 2015 (HealthDay News) -- A common Parkinson's disease medication might hold potential for preventing or ...

  2. Cuba shows jump in HIV positives.

    PubMed

    Cuba experienced a substantial increase in the number of HIV cases in 1996 due primarily to a growth of foreign tourism and an increase in prostitution, health officials said. The Juventud Rebelde newspaper said that since HIV/AIDS testing began in 1985, government-run hospitals and clinics have detected 1609 HIV-positive cases. In 1995 the total was reported at 1196, meaning that 413 new cases were detected in 1996. This compared with only 97 new cases reported during 1995. HIV infection among the island's 11 million inhabitants has remained relatively low due to a massive testing program and a public health infrastructure that provides universal and free medical treatment. Cuba was a pioneer in the use of interferon on those testing HIV-positive. Cuba produces its own interferon, which prolongs the life expectancy of patients, and also reagents for AIDS testing. There are special sanitariums for AIDS patients in most of Cuba's 12 provinces. Cuban adults who test HIV-positive are required to enter the sanitarium in a policy reminiscent of the way tuberculosis patients were tested in the US earlier in this century. Officials said the isolation of patients in sanitariums has been somewhat relaxed over past years by introducing greater flexibility in allowing persons who are considered reliable to live at home or make prolonged visits. PMID:12292465

  3. Use of Preventative and Therapeutic Drugs in Show Market Animals 

    E-print Network

    Faries Jr., Floron C.

    2001-03-12

    Various medicines are used in show market livestock and poultry, but exhibitors must ensure that the carcasses do not contain illegal residues of drugs, chemicals and feed additives. Only approved substances should be used. Illegal uses of drugs...

  4. FEATURE A. CONCRETE ANTIAIRCRAFT GUN POSITION, SHOWING CORAL RUBBLE BERM, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FEATURE A. CONCRETE ANTI-AIRCRAFT GUN POSITION, SHOWING CORAL RUBBLE BERM, VIEW FACING SOUTHEAST. - Naval Air Station Barbers Point, Battery-Anti-Aircraft Gun Position, South of Point Cruz Road & west of Coral Sea Road, Ewa, Honolulu County, HI

  5. FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING SOUTH. - Naval Air Station Barbers Point, Anti-Aircraft Battery Complex-Large Gun Position, East of Coral Sea Road, northwest of Hamilton Road, Ewa, Honolulu County, HI

  6. New drugs for Gram-positive uropathogens.

    PubMed

    Wagenlehner, F M E; Naber, K G

    2004-09-01

    Complicated urinary tract infections (UTIs) are frequent nosocomial infections. The bacterial spectrum encompasses Gram-negative but also Gram-positive pathogens in up to 30-40%. The existing treatment for Gram-positive pathogens is not always optimal. Antimicrobials for the treatment of Gram-positive uropathogens comprise older agents, such as aminopenicillins with or without beta-lactamase inhibitors and vancomycin, as well as newer fluoroquinolones, such as levofloxacin or gatifloxacin. However, resistant bacteria such as vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA) (except vancomycin-resistant) are generally also not susceptible to the fluoroquinolones. Therefore new agents need to be assessed in the treatment of UTI. Daptomycin and linezolid are new antimicrobial agents with good efficacy against Gram-positive uropathogens as shown by their minimal inhibitory concentrations. In a phase II study the urinary bactericidal activity of linezolid versus ciprofloxacin in volunteers showed comparable activity of both drugs against fluoroquinolone susceptible Gram-positive uropathogens, whereas linezolid was also as active against fluoroquinolone resistant ones. The pharmacokinetics and the mode of action of these two antibiotics are discussed together with some clinical data in the context of therapeutic use in patients with complicated UTIs. PMID:15364305

  7. Family Checkup: Positive Parenting Prevents Drug Abuse

    MedlinePLUS

    ... conflicts with your teenager and work toward a solution? Are you able to calmly set limits when ... Family Checkup: Positive Parenting Prevents Drug Abuse Question 1: Communication Question 2: Encouragement Question 3: Negotiation Question ...

  8. New Drug Shows Mixed Results Against Early Alzheimer's

    MedlinePLUS

    ... Alzheimer’s Drug Can Cholesterol Medicines Treat Alzheimer’s Disease? Gene Therapy Shows Promise Against Alzheimer’s Vitamins, Drugs Of Limited ... Benefits for Aricept Understanding the Stem Cell Debate Gene Therapy Hints at New Approach to Alzheimer’s Treatment Can ...

  9. FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING SOUTH (with scale stick). - Naval Air Station Barbers Point, Anti-Aircraft Battery Complex-Large Gun Position, East of Coral Sea Road, northwest of Hamilton Road, Ewa, Honolulu County, HI

  10. 4. INTERIOR, SHOWING HOIST IN POSITION NEXT TO WINDOW FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. INTERIOR, SHOWING HOIST IN POSITION NEXT TO WINDOW FOR VIEWING TAILINGS PILE, SLOT IN FRONT WALL FOR VIEWING HEADFRAME. - A. D. Wilcox Drift Mine, Boiler Cabin, Linda Creek near Dalton Highway, Bettles, Yukon-Koyukuk Census Area, AK

  11. 4. VENTILATION FAN SHOWING RELATIVE POSITION IN THE AIR TUNNEL. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VENTILATION FAN SHOWING RELATIVE POSITION IN THE AIR TUNNEL. - Hot Springs National Park, Bathhouse Row, Ozark Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

  12. 38. VIEW SHOWING 'CATFISH' SILO ELEVATOR IN UP POSITION, LOOKING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. VIEW SHOWING 'CATFISH' SILO ELEVATOR IN UP POSITION, LOOKING NORTHWEST Everett Weinreb, photographer, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

  13. Experimental Lung Cancer Drug Shows Early Promise | Poster

    Cancer.gov

    By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

  14. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.

    PubMed

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa; Gamarro, Francisco; Pérez-Victoria, José M

    2015-10-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca(2+), and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. PMID:26195527

  15. 5. UNIT VENTILATOR, MEN'S BATH HALL, SHOWING POSITION AGAINST WALL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. UNIT VENTILATOR, MEN'S BATH HALL, SHOWING POSITION AGAINST WALL ABOVE THE BATHS. - Hot Springs National Park, Bathhouse Row, Ozark Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

  16. Showing partial side view of swing span in closed position. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Showing partial side view of swing span in closed position. The two (2) arms act as simple spans, a small amount of negative bending is accommodated by the continous top and bottom truss chords due to a continuous condition. Note the inclined end post of each of the simple spans, the operator's house, center/pivot pier and the pivotal pole-line pole placed atop of bridge. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  17. Showing partial side view of swing bridge in open position. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Showing partial side view of swing bridge in open position. The operator's house is in the center of the truss bridge, directly over the center/pivot stone masonry pier. Note the two (2) center supports with the truss loads being delivered to the drum by a system of distributing girders. The swing bridge revolved on a cylindrical drum supported by rollers running on a circular track on the center/pivot pier. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  18. 49 CFR 219.605 - Positive drug test results; procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b)...

  19. 49 CFR 219.605 - Positive drug test results; procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b)...

  20. 49 CFR 219.605 - Positive drug test results; procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b)...

  1. 49 CFR 219.605 - Positive drug test results; procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Positive drug test results; procedures. 219.605 Section 219.605 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug...

  2. Rethinking drug policy: an integrity preserving compromise position 

    E-print Network

    Crispino, Azzurra

    2006-10-30

    The "War on Drugs" has been raging for twenty years without resolution. This work attempts to provide a compromise position between the prohibitionists and the legalizers that preserves the integrity of both positions. This compromise position...

  3. Is a positive history of non-anaesthetic drug allergy a predictive factor for positive allergy tests to anaesthetics?

    PubMed Central

    Hagau, Natalia; Gherman-Ionica, Nadia; Hagau, Denisa; Tranca, Sebastian; Sfichi, Manuela; Longrois, Dan

    2012-01-01

    AIMS International recommendations stipulate not performing screening skin tests to a drug in the absence of a clinical history consistent with that specific drug allergy. Nevertheless, two publications showed that a positive history of non-anaesthetic drug allergy was the only predictive factor for a positive skin test when screening for allergy to anaesthetic drugs was done. We selected from a surgical population 40 volunteers with a prior history of allergy to non-anaesthetic drugs in order to analyse the prevalence of positive allergy tests to anaesthetics. METHODS The selected adult patients were tested for 11 anaesthetic drugs using in vivo tests: skin prick (SPT) and intradermal (IDT) tests and in vitro tests: the basophil activation test (BAT) and detection of drug-specific immunoglobulin E (IgE). RESULTS The prevalence for the positive SPT and IDT was 1.6% and 5.8% respectively. The result of flow cytometry agreed with the SPT in five out of seven positive SPT (71%). IgEs confirmed two positive SPT with corresponding positive BAT. Ten per cent of the patients had a positive prick test to neuromuscular blocking agents (NMBA). For midazolam none of the SPT was positive, but 11 patients had positive IDT nonconfirmed by BAT. CONCLUSION The prevalence of positive in vivo and in vitro allergy tests to NMBAs is higher in our study population. This could be an argument for pre-operative SPT to NMBAs for the surgical population with reported non-anaesthetic drug allergies. A larger prospective study is needed to validate changes in clinical practice. PMID:21988224

  4. Drug Failure: The Theoretical Position of the Drop-Out.

    ERIC Educational Resources Information Center

    Vedder, Charles B.

    This paper examines the theoretical position of the person who drops out of illegal drug use. A person was considered a drop-out if he admittedly no longer used any or all the drugs in the following categories: marijuana, hallucinogens, speed, downers, and inhalants. A purposive sample was drawn to capture as many people fitting this criterion as…

  5. Studies Show Microenvironment Plays Key Role in Anticancer Drug Resistance | Physical Sciences in Oncology

    Cancer.gov

    As mounting evidence continues to show that evolutionary selective pressure will ultimately drive cancer cells to develop resistance to drug therapies, cancer researchers are looking for new treatment paradigms that might avoid or surmount drug resistance. One promising approach aims to better understand how the microenvironment surrounding a tumor impacts drug resistance and use that knowledge to create novel strategies for attacking tumors.

  6. [A case of drug-induced pulmonary injury showing organizing pneumonia pattern due to S-1].

    PubMed

    Nakata, Hiroaki; Shinano, Hideki; Kuraya, Daisuke; Fujioka, Yasunori

    2012-06-01

    Reported here is the case of a 76-year-old male with gastric cancer. Distal gastrectomy was performed after his admission to our hospital. Histopathologically, the cancer was determined to be in the advanced stage. Combination chemotherapy with CDDP and S-1 was administered for 6 courses, after which S-1 was used alone. Chest X-ray and CT showed multiple dispersed lesions in the lung. Further examination by bronchoscope was performed. Histopathological examination of a biopsy specimen revealed the lesion to be organizing pneumonia. A drug-induced lymphocyte stimulation test (DLST) for S-1 proved to be positive. Discontinuation of S-1 administration led to natural improvement of the pneumonia. These results suggest that S-1 had induced the organizing pneumonia. PMID:22705691

  7. New Study Shows Clinicians Under-Prescribing Flu Antiviral Drugs and Possibly Overprescribing Antibiotics

    MedlinePLUS

    ... this? Submit What's this? Submit Button Past Newsletters New Study Shows Clinicians Under-Prescribing Flu Antiviral Drugs ... Tweet Share Compartir July 17, 2014 â?? A new study of flu treatment practices during the 2012- ...

  8. The new tuberculosis drug Perchlozone® shows cross-resistance with thiacetazone.

    PubMed

    Gopal, Pooja; Dick, Thomas

    2015-04-01

    Perchlozone(®) (PCZ), a new thiosemicarbazone developed by JSC Pharmasyntez (Moscow, Russia) for the treatment of tuberculosis (TB), was approved for use against multidrug-resistant disease in Russia in 2012. The mechanism of action of the drug is unknown. A well-studied thiosemicarbazone is the old TB drug thiacetazone (TAC). It has a narrow spectrum and inhibits the FASII dehydratase complex HadABC, which is involved in cell wall biosynthesis in Mycobacterium tuberculosis. TAC is a prodrug, requiring activation by the monooxygenase EthA. In this study, a comparative in vitro analysis of both drugs was performed. The two compounds had an identical spectrum of activity, spontaneous resistant mutants showed cross-resistance, and resistance was mapped to HadABC and EthA. These results suggest that PCZ, like TAC, is a prodrug and that both drugs share EthA as an activating enzyme and HadABC as their principal target. PMID:25704063

  9. Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis.

    PubMed

    Mescam-Mancini, Lénaig; Allenbach, Yves; Hervier, Baptiste; Devilliers, Hervé; Mariampillay, Kuberaka; Dubourg, Odile; Maisonobe, Thierry; Gherardi, Romain; Mezin, Paulette; Preusse, Corinna; Stenzel, Werner; Benveniste, Olivier

    2015-09-01

    Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy has a specific morphological phenotype. In a series of 53 muscle biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria defining a characteristic morphological pattern were identified. They were tested in a second series of anti-Jo-1 antibody-positive patients and compared to 63 biopsies from patients suffering from other idiopathic inflammatory myopathies. In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly clustered in perifascicular regions, were frequently observed. Sarcolemmal complement deposition was detected specifically in perifascicular areas. Inflammation was mainly located in the perimysium and around vessels in 90.6%. Perimysial fragmentation was observed in 90% of cases. Major histocompatibility complex class I staining was diffusely positive, with a perifascicular reinforcement. Multivariate analysis showed that criteria defining perifascicular pathology: perifascicular necrosis, atrophy, and perimysial fragmentation allow the distinction of anti-Jo-1 antibody-positive patients, among patients suffering from other idiopathic inflammatory myopathies. Anti-Jo-1 antibody-positive patients displayed perifascicular necrosis, whereas dermatomyositis patients exhibited perifascicular atrophy. PMID:26198592

  10. IET. Tank building (TAN627). Plans, elevation, details. shows position of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    IET. Tank building (TAN-627). Plans, elevation, details. shows position of tanks within building and concrete supports. Ralph M. Parsons 902-4-ANP-627-A&S 420. Date: Fabruary 1954. Approved by INEEL Classification Office for public release. INEEL index code no. 035-0627-00-693-106975 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  11. The Position of Moving Objects Eagleman and Sejnowski (1) showed that the

    E-print Network

    The Position of Moving Objects Eagleman and Sejnowski (1) showed that the flash-lag effect (2, 3)--a visual illusion in which two objects physically at the same loca- tion appear to be offset because for flashed and moving objects (5­7). Our work, like theirs, has found that the flash-lag effect is due

  12. Legal Position of School Personnel -- Drugs and Narcotics.

    ERIC Educational Resources Information Center

    Shannon, Thomas A.

    California educators have been given broad discretionary powers to control students who misuse drugs or narcotics, and to develop drug education programs. This paper outlines and discusses legislation dealing with disciplinary actions against drug offenders, and delineates school responsibilities for developing and implementing effective drug

  13. This book describes the responsibilities of show personnel and outlines the job descriptions of various positions for the NH 4-H State Horse Show (or any other 4-H horse show).

    E-print Network

    New Hampshire, University of

    of various positions for the NH 4-H State Horse Show (or any other 4-H horse show). June 2013 #12;Table of Contents Organizing a 4-H Horse Show ........................................................................................... 1 State 4-H Horse Show Philosophy................................................................ 1

  14. Fatal Crashes from Drivers Testing Positive for Drugs in the U.S., 1993–2010

    PubMed Central

    Stimpson, Jim P.; Pagán, José A.

    2014-01-01

    Objective Illegal drug use is a persistent problem, prescription drug abuse is on the rise, and there is clinical evidence that drug use reduces driving performance. This study describes trends in characteristics of drivers involved in fatal motor vehicle crashes who test positive for drugs. Methods We used the Fatality Analysis Reporting System—a census of motor vehicle crashes resulting in at least one fatality on U.S. public roads—to investigate suspected drug use for the period 1993–2010. Results Drugged drivers who were tested for drug use accounted for 11.4% of all drivers involved in fatal motor vehicle crashes in 2010. Drugged drivers are increasingly likely to be older drivers, and the percentage using multiple drugs increased from 32.6% in 1993 to 45.8% in 2010. About half (52.4%) of all drugged drivers used alcohol, but nearly three-quarters of drivers testing positive for cocaine also used alcohol. Prescription drugs accounted for the highest fraction of drugs used by drugged drivers in fatal crashes in 2010 (46.5%), with much of the increase in prevalence occurring since the mid-2000s. Conclusions The profile of a drugged driver has changed substantially over time. An increasing share of these drivers is now testing positive for prescription drugs, cannabis, and multiple drugs. These findings have implications for developing interventions to address the changing nature of drug use among drivers in the U.S. PMID:24982537

  15. Novel Drug Delivery System Shows Early Promise for Treating Lupus in Mice

    MedlinePLUS

    ... Lupus in Mice A drug delivery system using nanoparticle technology that allows for better targeting of specific ... be effectively programmed to seek specific cells. Although nanoparticle drug delivery systems have been used experimentally to ...

  16. Positively Charged Polyethylenimines Enhance Nasal Absorption of the Negatively Charged Drug, Low Molecular Weight Heparin

    PubMed Central

    Yang, Tianzhi; Hussain, Alamdar; Bai, Shuhua; Khalil, Ikramy A.; Harashima, Hideyoshi; Ahsan, Fakhrul

    2007-01-01

    This study tests the hypothesis that positively charged polyethylenimines (PEIs) enhance nasal absorption of low molecular weight heparin (LMWH) by reducing the negative surface charge of the drug molecule. Physical interactions between PEIs and LMWH were studied by Fourier transform infrared (FTIR) spectroscopy, particle size analysis, conductivity measurements, zeta potential analysis, and azure A assay. The efficacy of PEIs in enhancing nasal absorption of LMWH was studied by administering LMWH formulated with PEI into the nose of anesthetized rats and monitoring drug absorption by measuring plasma anti-factor Xa activity. The metabolic stability of LMWH was evaluated by incubating the drug in rat nasal mucosal homogenates. FTIR spectra of the LMWH-PEI formulation showed a shift in peak position compared to LMWH or PEI alone. Decreases in conductivity, zeta potential and the amount of free LMWH in the PEI-LMWH formulation, as revealed by azure A assay, suggest that PEIs possibly neutralize the negative surface charge of LMWH. The efficacy of PEI in enhancing the bioavailability of nasally administered LMWH can be ranked as PEI-1000 KDa ? PEI-750 KDa > PEI-25 KDa. When PEI-1000 KDa was used at a concentration of 0.25%, there was a 4-fold increase in both the absolute and relative bioavailabilities of LMWH compared to the control formulation. Overall, these results indicate that polyethylenimines can be used as potential carriers for nasally administered LMWHs. PMID:17023085

  17. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase.

    PubMed

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2015-10-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 µM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl(-) and the decreased HCO3 (-) concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na-K-2Cl electroneutral cotransporter or Cl(-)/HCO3 (-) anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  18. Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

    PubMed Central

    Lepesheva, Galina I.

    2013-01-01

    Introduction Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14?-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. PMID:24079515

  19. Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment.

    PubMed

    Chirio, Daniela; Gallarate, Marina; Peira, Elena; Battaglia, Luigi; Muntoni, Elisabetta; Riganti, Chiara; Biasibetti, Elena; Capucchio, Maria Teresa; Valazza, Alberto; Panciani, Pierpaolo; Lanotte, Michele; Annovazzi, Laura; Caldera, Valentina; Mellai, Marta; Filice, Gaetano; Corona, Silvia; Schiffer, Davide

    2014-11-01

    Paclitaxel loaded solid lipid nanoparticles (SLN) of behenic acid were prepared with the coacervation technique. Generally, spherical shaped SLN with mean diameters in the range 300–600 nm were obtained. The introduction of charged molecules, such as stearylamine and glycol chitosan into the formulation allowed to obtain positive SLN with Zeta potential in the 8-20 mV range and encapsulation efficiency in the 25–90% range.Blood–brain barrier (BBB) permeability, tested in vitro through hCMEC/D3 cells monolayer, showed a significantly increase in the permeation of Coumarin-6, used as model drug, when vehicled in SLN. Positive-charged SLN do not seem to enhance permeation although stearylamine-positive SLN resulted the best permeable formulation after 24 h.Cytotoxicity studies on NO3 glioblastoma cell line demonstrated the maintenance of cytotoxic activity of all paclitaxel-loaded SLN that was always unmodified or greater compared with free drug. No difference in cytotoxicity was noted between neutral and charged SLN.Co-culture experiments with hCMEC/D3 and different glioblastoma cells evidenced that, when delivered in SLN, paclitaxel increased its cytotoxicity towards glioblastoma cells. PMID:25445304

  20. Imaging Shows Microenvironment Impacts Tumor Drug Resistance | Physical Sciences in Oncology

    Cancer.gov

    It should be possible to significantly improve the response of common cancers to existing “classical” chemotherapy drugs, say scientists at Cold Spring Harbor Laboratory (CSHL). Accomplishing this feat will require combining conventional chemotherapy regimes with agents that alter the interaction of cancer cells with their immediate surroundings, called the tumor microenvironment.

  1. NIH-supported trial drug shows benefit in children with previously treated cancers

    Cancer.gov

    Young patients with some types of advanced cancer, for whom standard treatment had failed, had their tumors disappear during treatment with a drug that both targets and blocks a protein associated with their disease. These findings are from a Phase I, mul

  2. False-positive interferences of common urine drug screen immunoassays: a review.

    PubMed

    Saitman, Alec; Park, Hyung-Doo; Fitzgerald, Robert L

    2014-09-01

    Urine drug screen (UDS) immunoassays are a quick and inexpensive method for determining the presence of drugs of abuse. Many cross-reactivities exist with other analytes, potentially causing a false-positive result in an initial drug screen. Knowledge of these potential interferents is important in determining a course of action for patient care. We present an inclusive review of analytes causing false-positive interferences with drugs-of-abuse UDS immunoassays, which covers the literature from the year 2000 to present. English language articles were searched via the SciFinder platform with the strings 'false positive [drug] urine' yielding 173 articles. These articles were then carefully analyzed and condensed to 62 that included data on causes of false-positive results. The discussion is separated into six sections by drug class with a corresponding table of cross-reacting compounds for quick reference. False-positive results were described for amphetamines, opiates, benzodiazepines, cannabinoids, tricyclic antidepressants, phencyclidine, lysergic acid diethylamide and barbiturates. These false-positive results support the generally accepted practice that immunoassay positive results are considered presumptive until confirmed by a second independent chemical technique. PMID:24986836

  3. Next-Generation Sequencing of Plasmodium vivax Patient Samples Shows Evidence of Direct Evolution in Drug-Resistance Genes

    PubMed Central

    Flannery, Erika L.; Wang, Tina; Akbari, Ali; Corey, Victoria C.; Gunawan, Felicia; Bright, A. Taylor; Abraham, Matthew; Sanchez, Juan F.; Santolalla, Meddly L.; Baldeviano, G. Christian; Edgel, Kimberly A.; Rosales, Luis A.; Lescano, Andrés G.; Bafna, Vineet; Vinetz, Joseph M.; Winzeler, Elizabeth A.

    2015-01-01

    Understanding the mechanisms of drug resistance in Plasmodium vivax, the parasite that causes the most widespread form of human malaria, is complicated by the lack of a suitable long-term cell culture system for this parasite. In contrast to P. falciparum, which can be more readily manipulated in the laboratory, insights about parasite biology need to be inferred from human studies. Here we analyze the genomes of parasites within 10 human P. vivax infections from the Peruvian Amazon. Using next-generation sequencing we show that some P. vivax infections analyzed from the region are likely polyclonal. Despite their polyclonality we observe limited parasite genetic diversity by showing that three or fewer haplotypes comprise 94% of the examined genomes, suggesting the recent introduction of parasites into this geographic region. In contrast we find more than three haplotypes in putative drug-resistance genes, including the gene encoding dihydrofolate reductase-thymidylate synthase and the P. vivax multidrug resistance associated transporter, suggesting that resistance mutations have arisen independently. Additionally, several drug-resistance genes are located in genomic regions with evidence of increased copy number. Our data suggest that whole genome sequencing of malaria parasites from patients may provide more insight about the evolution of drug resistance than genetic linkage or association studies, especially in geographical regions with limited parasite genetic diversity. PMID:26719854

  4. Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma.

    PubMed

    Oesch, Susanne; Walter, Dagmar; Wachtel, Marco; Pretre, Kathya; Salazar, Maria; Guzmán, Manuel; Velasco, Guillermo; Schäfer, Beat W

    2009-07-01

    Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma. PMID:19509271

  5. Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children.

    PubMed

    Kaplan, Justin; Shah, Pooja; Faley, Brian; Siegel, Mark E

    2015-12-01

    Urine drug screens (UDSs) are used to identify the presence of certain medications. One limitation of UDSs is the potential for false-positive results caused by cross-reactivity with other substances. Amphetamines have an extensive list of cross-reacting medications. The literature contains reports of false-positive amphetamine UDSs with multiple antidepressants and antipsychotics. We present 2 cases of presumed false-positive UDSs for amphetamines after ingestion of aripiprazole. Case 1 was a 16-month-old girl who accidently ingested 15 to 45 mg of aripiprazole. She was lethargic and ataxic at home with 1 episode of vomiting containing no identifiable tablets. She remained sluggish with periods of irritability and was admitted for observation. UDS on 2 consecutive days came back positive for amphetamines. Case 2 was of a 20-month-old girl who was brought into the hospital after accidental ingestion of an unknown quantity of her father's medications which included aripiprazole. UDS on the first day of admission came back positive only for amphetamines. Confirmatory testing with gas chromatography-mass spectrometry (GC-MS) on the blood and urine samples were also performed for both patients on presentation to detect amphetamines and were subsequently negative. Both patients returned to baseline and were discharged from the hospital. To our knowledge, these cases represent the first reports of false-positive amphetamine urine drug tests with aripiprazole. In both cases, aripiprazole was the drug with the highest likelihood of causing the positive amphetamine screen. The implications of these false-positives include the possibility of unnecessary treatment and monitoring of patients. PMID:26527556

  6. Genome Wide Nucleosome Mapping for HSV-1 Shows Nucleosomes Are Deposited at Preferred Positions during Lytic Infection

    PubMed Central

    Oh, Jaewook; Sanders, Iryna F.; Chen, Eric Z.; Li, Hongzhe; Tobias, John W.; Isett, R. Benjamin; Penubarthi, Sindura; Sun, Hao; Baldwin, Don A.; Fraser, Nigel W.

    2015-01-01

    HSV is a large double stranded DNA virus, capable of causing a variety of diseases from the common cold sore to devastating encephalitis. Although DNA within the HSV virion does not contain any histone protein, within 1 h of infecting a cell and entering its nucleus the viral genome acquires some histone protein (nucleosomes). During lytic infection, partial micrococcal nuclease (MNase) digestion does not give the classic ladder band pattern, seen on digestion of cell DNA or latent viral DNA. However, complete digestion does give a mono-nucleosome band, strongly suggesting that there are some nucleosomes present on the viral genome during the lytic infection, but that they are not evenly positioned, with a 200bp repeat pattern, like cell DNA. Where then are the nucleosomes positioned? Here we perform HSV-1 genome wide nucleosome mapping, at a time when viral replication is in full swing (6hr PI), using a microarray consisting of 50mer oligonucleotides, covering the whole viral genome (152kb). Arrays were probed with MNase-protected fragments of DNA from infected cells. Cells were not treated with crosslinking agents, thus we are only mapping tightly bound nucleosomes. The data show that nucleosome deposition is not random. The distribution of signal on the arrays suggest that nucleosomes are located at preferred positions on the genome, and that there are some positions that are not occupied (nucleosome free regions -NFR or Nucleosome depleted regions -NDR), or occupied at frequency below our limit of detection in the population of genomes. Occupancy of only a fraction of the possible sites may explain the lack of a typical MNase partial digestion band ladder pattern for HSV DNA during lytic infection. On average, DNA encoding Immediate Early (IE), Early (E) and Late (L) genes appear to have a similar density of nucleosomes. PMID:25710170

  7. Genome wide nucleosome mapping for HSV-1 shows nucleosomes are deposited at preferred positions during lytic infection.

    PubMed

    Oh, Jaewook; Sanders, Iryna F; Chen, Eric Z; Li, Hongzhe; Tobias, John W; Isett, R Benjamin; Penubarthi, Sindura; Sun, Hao; Baldwin, Don A; Fraser, Nigel W

    2015-01-01

    HSV is a large double stranded DNA virus, capable of causing a variety of diseases from the common cold sore to devastating encephalitis. Although DNA within the HSV virion does not contain any histone protein, within 1 h of infecting a cell and entering its nucleus the viral genome acquires some histone protein (nucleosomes). During lytic infection, partial micrococcal nuclease (MNase) digestion does not give the classic ladder band pattern, seen on digestion of cell DNA or latent viral DNA. However, complete digestion does give a mono-nucleosome band, strongly suggesting that there are some nucleosomes present on the viral genome during the lytic infection, but that they are not evenly positioned, with a 200 bp repeat pattern, like cell DNA. Where then are the nucleosomes positioned? Here we perform HSV-1 genome wide nucleosome mapping, at a time when viral replication is in full swing (6 hr PI), using a microarray consisting of 50mer oligonucleotides, covering the whole viral genome (152 kb). Arrays were probed with MNase-protected fragments of DNA from infected cells. Cells were not treated with crosslinking agents, thus we are only mapping tightly bound nucleosomes. The data show that nucleosome deposition is not random. The distribution of signal on the arrays suggest that nucleosomes are located at preferred positions on the genome, and that there are some positions that are not occupied (nucleosome free regions -NFR or Nucleosome depleted regions -NDR), or occupied at frequency below our limit of detection in the population of genomes. Occupancy of only a fraction of the possible sites may explain the lack of a typical MNase partial digestion band ladder pattern for HSV DNA during lytic infection. On average, DNA encoding Immediate Early (IE), Early (E) and Late (L) genes appear to have a similar density of nucleosomes. PMID:25710170

  8. Automated tracking of mitotic spindle pole positions shows that LGN is required for spindle rotation but not orientation maintenance

    PubMed Central

    Corrigan, Adam M; Shrestha, Roshan L; Zulkipli, Ihsan; Hiroi, Noriko; Liu, Yingjun; Tamura, Naoka; Yang, Bing; Patel, Jessica; Funahashi, Akira; Donald, Athene; Draviam, Viji M

    2013-01-01

    Spindle orientation defines the plane of cell division and, thereby, the spatial position of all daughter cells. Here, we develop a live cell microscopy-based methodology to extract spindle movements in human epithelial cell lines and study how spindles are brought to a pre-defined orientation. We show that spindles undergo two distinct regimes of movements. Spindles are first actively rotated toward the cells’ long-axis and then maintained along this pre-defined axis. By quantifying spindle movements in cells depleted of LGN, we show that the first regime of rotational movements requires LGN that recruits cortical dynein. In contrast, the second regime of movements that maintains spindle orientation does not require LGN, but is sensitive to 2ME2 that suppresses microtubule dynamics. Our study sheds first insight into spatially defined spindle movement regimes in human cells, and supports the presence of LGN and dynein independent cortical anchors for astral microtubules. PMID:23907121

  9. Automated tracking of mitotic spindle pole positions shows that LGN is required for spindle rotation but not orientation maintenance.

    PubMed

    Corrigan, Adam M; Shrestha, Roshan L; Zulkipli, Ihsan; Hiroi, Noriko; Liu, Yingjun; Tamura, Naoka; Yang, Bing; Patel, Jessica; Funahashi, Akira; Donald, Athene; Draviam, Viji M

    2013-08-15

    Spindle orientation defines the plane of cell division and, thereby, the spatial position of all daughter cells. Here, we develop a live cell microscopy-based methodology to extract spindle movements in human epithelial cell lines and study how spindles are brought to a pre-defined orientation. We show that spindles undergo two distinct regimes of movements. Spindles are first actively rotated toward the cells' long-axis and then maintained along this pre-defined axis. By quantifying spindle movements in cells depleted of LGN, we show that the first regime of rotational movements requires LGN that recruits cortical dynein. In contrast, the second regime of movements that maintains spindle orientation does not require LGN, but is sensitive to 2ME2 that suppresses microtubule dynamics. Our study sheds first insight into spatially defined spindle movement regimes in human cells, and supports the presence of LGN and dynein independent cortical anchors for astral microtubules. PMID:23907121

  10. Position paper of Italian rheumatologists on the use of biosimilar drugs.

    PubMed

    Atzeni, Fabiola; Sebastiani, Marco; Ricci, Cristian; Celano, Antonella; Gremese, Elisa; Iannone, Florenzo; Meroni, Pier Luigi; Minghetti, Paola; Sarzi-Puttini, Piercarlo; Ferraccioli, Gianfranco; Lapadula, Giovanni

    2015-01-01

    The recent availability of biosimilars as a result of the expiry of the patents of first-generation biotechnological drugs may theoretically reduce the direct costs of such treatments, making their use accessible to a larger number of patients. However, the currently available clinical data refer to a relatively small number of patients, and do not provide sufficient information concerning long-term efficacy and safety or the frequency of rare adverse events. Given the importance of the introduction of biosimilar drugs and the limitations of our current knowledge of their efficacy and safety profiles, we believe it is mandatory to draw up a position paper for Italian Rheumatologists. Moreover, in order to guarantee their safety, it is mandatory to indicate behavioural rules for the involved specialists and competent authorities, and perform ad hoc clinical trials and appropriate drug surveillance. PMID:25436597

  11. Postdoctoral Position at the University of Idaho: Evolution of drug resistance plasmid persistence in biofilms

    E-print Network

    Top, Eva

    . The goal of this project is to gain insight into the evolutionary mechanisms by which multi-drug resistance the supervision of Dr. Eva Top (Professor of Biological Sciences, evatop@uidaho.edu) and in collaboration with Drs://www.ibest.uidaho.edu/ibest/index.html). The project will be funded by a two-year grant from the Department of the Army and the position should

  12. Oral fluid testing for drugs of abuse: positive prevalence rates by Intercept immunoassay screening and GC-MS-MS confirmation and suggested cutoff concentrations.

    PubMed

    Cone, Edward J; Presley, Lance; Lehrer, Michael; Seiter, William; Smith, Melissa; Kardos, Keith W; Fritch, Dean; Salamone, Sal; Niedbala, R Sam

    2002-01-01

    Draft guidelines for the use of oral fluid for workplace drug testing are under development by the Substance Abuse and Mental Health Services Administration (SAMHSA) in cooperation with industry and researchers. Comparison studies of the effectiveness of oral fluid testing versus urine testing are needed to establish scientifically reliable cutoff concentrations for oral fluid testing. We present the results of the first large scale database on oral fluid testing in private industry. A total of 77,218 oral fluid specimens were tested over the period of January through October 2001 at LabOne. Specimens were screened by Intercept immunoassay at manufacturer's recommended cutoff concentrations for the five SAMHSA drug categories (marijuana, cocaine, opiates, phencyclidine, and amphetamines). Presumptive positive specimens were confirmed by gas chromatography-tandem mass spectrometry. A total of 3908 positive tests were reported over the 10-month period, representing a positive rate of 5.06%. Of the five drug categories, marijuana and cocaine accounted for 85.75% of the positives. The pattern and frequency of drug positives showed remarkable similarity to urine drug prevalence rates reported for the general workforce according to the Quest Diagnostics' Drug Testing Index over the same general period, suggesting that oral fluid testing produces equivalent results to urine testing. The data on oral fluid testing also revealed a surprisingly high 66.7% prevalence of 6-acetylmorphine confirmations for morphine positives suggesting that oral fluid testing may be superior in some cases to urine testing. Comparison of oral fluid drug concentrations to SAMHSA-recommended cutoff concentrations in Draft Guidelines indicated that adoption of the screening and confirmation cutoff concentrations of Draft Guidelines #3 would produce the most consistent reporting results for all drug classes except amphetamines. Consequently, it is suggested that the final Guidelines adopt the screening and cutoff concentrations listed in Draft Guidelines #3 with the exception of lowering the amphetamines cutoff concentrations (screening/confirmation) to 50/50 ng/mL for amphetamine and methamphetamine. PMID:12501910

  13. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients

    PubMed Central

    Gajiwala, Ketan S.; Wu, Joe C.; Christensen, James; Deshmukh, Gayatri D.; Diehl, Wade; DiNitto, Jonathan P.; English, Jessie M.; Greig, Michael J.; He, You-Ai; Jacques, Suzanne L.; Lunney, Elizabeth A.; McTigue, Michele; Molina, David; Quenzer, Terri; Wells, Peter A.; Yu, Xiu; Zhang, Yan; Zou, Aihua; Emmett, Mark R.; Marshall, Alan G.; Zhang, Hui-Min; Demetri, George D.

    2009-01-01

    Most gastrointestinal stromal tumors (GISTs) exhibit aberrant activation of the receptor tyrosine kinase (RTK) KIT. The efficacy of the inhibitors imatinib mesylate and sunitinib malate in GIST patients has been linked to their inhibition of these mutant KIT proteins. However, patients on imatinib can acquire secondary KIT mutations that render the protein insensitive to the inhibitor. Sunitinib has shown efficacy against certain imatinib-resistant mutants, although a subset that resides in the activation loop, including D816H/V, remains resistant. Biochemical and structural studies were undertaken to determine the molecular basis of sunitinib resistance. Our results show that sunitinib targets the autoinhibited conformation of WT KIT and that the D816H mutant undergoes a shift in conformational equilibrium toward the active state. These findings provide a structural and enzymologic explanation for the resistance profile observed with the KIT inhibitors. Prospectively, they have implications for understanding oncogenic kinase mutants and for circumventing drug resistance. PMID:19164557

  14. False positive in the IV drug self-administration test in C57BL/6J mice

    PubMed Central

    Thomsen, Morgane; Caine, S. Barak

    2011-01-01

    The objective of the present study was to examine C57BL/6J (B6) mice during extinction conditions, following food training, for rates and patterns of operant behavior that appear similar to behavior maintained by IV cocaine injections. The rationale was to evaluate the potential for false positives in the IV self-administration test using protocols common in studies of knockout mice backcrossed to B6. An additional aim was to assess the influence of food- and drug- associated cues and mouse strain. Mice were allowed to acquire lever pressing reinforced by sweetened condensed milk under a fixed ratio (FR) 1 then FR 2 schedule of reinforcement accompanied by a flashing light. A catheter base was then implanted for simulation of IV self-administration conditions. Mice were allowed to lever press with cues remaining the same as during food training but without further scheduled consequences (i.e., no drug or food reinforcers delivered). All mice sustained lever pressing for several weeks, and over half met commonly used criteria for “self-administration behavior”. Thus B6 mice showed perseveration of a previously reinforced behavior that closely resembled rates and patterns of drug self-administration. This effect in B6 mice was greater than with A/J mice, and the lack of extinction was even more robust in the presence of cocaine-associated cues than with food-associated cues. We suggest that a necessary criteria for positive results in the IV drug self-administration test include an increase in responding when cocaine is made available after extinction with saline self-administration. PMID:21522054

  15. FUNCTIONAL ANALYSIS OF A NOVEL POSITIVE ALLOSTERIC MODULATOR OF AMPA RECEPTORS DERIVED FROM A STRUCTURE-BASED DRUG DESIGN STRATEGY

    PubMed Central

    Harms, Jonathan E.; Benveniste, Morris; Maclean, John K. F.; Partin, Kathryn M.; Jamieson, Craig

    2012-01-01

    Positive allosteric modulators of ?-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket. Here, we describe the electrophysiological properties of a new chemotype derived from a structure-based drug design strategy (SBDD), which makes similar receptor interactions compared to previously reported classes of modulator. This pyrazole amide derivative, JAMI1001A, with a promising developability profile, efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms. PMID:22735771

  16. Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients

    PubMed Central

    Okparavero, Aghogho A; Tighiouart, Hocine; Krishnasami, Zipporah; Wyatt, Christina M; Graham, Hiba; Hellinger, James; Inker, Lesley A

    2014-01-01

    Background Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. Methods We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. Results For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared to recommended dosages based on the level of estimated kidney function, 3% to 19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. Conclusions The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function. PMID:23963249

  17. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, Mbj

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety. PMID:25721922

  18. Urine Toxicology Screen in Multiple Sleep Latency Test: The Correlation of Positive Tetrahydrocannabinol, Drug Negative Patients, and Narcolepsy

    PubMed Central

    Dzodzomenyo, Samuel; Stolfi, Adrienne; Splaingard, Deborah; Earley, Elizabeth; Onadeko, Oluwole; Splaingard, Mark

    2015-01-01

    Objective: Drugs can influence results of multiple sleep latency tests (MSLT). We sought to identify the effect of marijuana on MSLT results in pediatric patients evaluated for excessive daytime sleepiness (EDS). Methods: This is a retrospective study of urine drug screens performed the morning before MSLT in 383 patients < 21 years old referred for EDS. MSLT results were divided into those with (1) (?) urine drug screens, (2) urine drug screens (+) for tetrahydrocannabinol (THC) alone or THC plus other drugs, and (3) urine drug screens (+) for drugs other than THC. Groups were compared with Fisher exact tests or one-way ANOVA. Results: 38 (10%) urine drug tests were (+): 14 for THC and 24 for other drugs. Forty-three percent of patients with drug screen (+) for THC had MSLT findings consistent with narcolepsy, 0% consistent with idiopathic hypersomnia, 29% other, and 29% normal. This was statistically different from those with (?) screens (24% narcolepsy, 20% idiopathic hypersomnia, 6% other, 50% normal), and those (+) for drugs other than THC (17% narcolepsy, 33% idiopathic hypersomnia, 4% other, 46% normal (p = 0.01). Six percent (6/93) of patients with MSLT findings consistent with narcolepsy were drug screen (+) for THC; 71% of patients with drug screen (+) for THC had multiple sleep onset REM periods (SOREMS). There were no (+) urine drug screens in patients < 13 years old. Conclusion: Many pediatric patients with (+) urine drug screens for THC met MSLT criteria for narcolepsy or had multiple SOREMs. Drug screening is important in interpreting MSLT findings for children ? 13 years. Citation: Dzodzomenyo S, Stolfi A, Splaingard D, Earley E, Onadeko O, Splaingard M. Urine toxicology screen in multiple sleep latency test: the correlation of positive tetrahydrocannabinol, drug negative patients, and narcolepsy. J Clin Sleep Med 2015;11(2):93–99. PMID:25348245

  19. The Drug User's Identity and How It Relates to Being Hepatitis C Antibody Positive: A Qualitative Study

    ERIC Educational Resources Information Center

    Copeland, Lorraine

    2004-01-01

    The increasing health problem of hepatitis C virus infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. injecting drug users). There is a lack of information about the knowledge, perceptions and feelings that injecting drug users hold about their hepatitis C antibody positive

  20. Positive allosteric modulators to peptide GPCRs: a promising class of drugs

    PubMed Central

    Bartfai, Tamas; Wang, Ming-wei

    2013-01-01

    The task of finding selective and stable peptide receptor agonists with low molecular weight, desirable pharmacokinetic properties and penetrable to the blood-brain barrier has proven too difficult for many highly coveted drug targets, including receptors for endothelin, vasoactive intestinal peptide and galanin. These receptors and ligand-gated ion channels activated by structurally simple agonists such as glutamate, glycine and GABA present such a narrow chemical space that the design of subtype-selective molecules capable of distinguishing a dozen of glutamate and GABA receptor subtypes and possessing desirable pharmacokinetic properties has also been problematic. In contrast, the pharmaceutical industry demonstrates a remarkable success in developing 1,4-benzodiazepines, positive allosteric modulators (PMAs) of the GABAA receptor. They were synthesized over 50 years ago and discovered to have anxiolytic potential through an in vivo assay. As exemplified by Librium, Valium and Dormicum, these allosteric ligands of the receptor became the world's first blockbuster drugs. Through molecular manipulation over the past 2 decades, including mutations and knockouts of the endogenous ligands or their receptors, and by in-depth physiological and pharmacological studies, more peptide and glutamate receptors have become well-validated drug targets for which an agonist is sought. In such cases, the pursuit for PAMs has also intensified, and a working paradigm to identify drug candidates that are designed as PAMs has emerged. This review, which focuses on the general principles of finding PAMs of peptide receptors in the 21st century, describes the workflow and some of its resulting compounds such as PAMs of galanin receptor 2 that act as potent anticonvulsant agents. PMID:23624758

  1. Three-Dimensional Repositioning Tasks Show Differences in Joint Position Sense between Active and Passive Shoulder Motion

    E-print Network

    Karduna, Andrew

    simultaneous mirroring movements, or the ipsilateral limb can be reused by recalling the placement position at the shoulder. ß 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30. The current belief is that muscle spindles, movement encoders in parallel with the muscle, are the predominant

  2. Dual Fatty Acid Synthase and HER2 Signaling Blockade Shows Marked Antitumor Activity against Breast Cancer Models Resistant to Anti-HER2 Drugs

    PubMed Central

    Blancafort, Adriana; Giró-Perafita, Ariadna; Oliveras, Glòria; Palomeras, Sònia; Turrado, Carlos; Campuzano, Òscar; Carrión-Salip, Dolors; Massaguer, Anna; Brugada, Ramon; Palafox, Marta; Gómez-Miragaya, Jorge; González-Suárez, Eva; Puig, Teresa

    2015-01-01

    Blocking the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of HER2-positive breast carcinoma cells. The hypothesis is that blocking FASN, in combination with anti-HER2 signaling agents, would be an effective antitumor strategy in preclinical HER2+ breast cancer models of trastuzumab and lapatinib resistance. We developed and molecularly characterized in vitro HER2+ models of resistance to trastuzumab (SKTR), lapatinib (SKLR) and both (SKLTR). The cellular interactions of combining anti-FASN polyphenolic compounds (EGCG and the synthetic G28UCM) with anti-HER2 signaling drugs (trastuzumab plus pertuzumab and temsirolimus) were analyzed. Tumor growth inhibition after treatment with EGCG, pertuzumab, temsirolimus or the combination was evaluated in two in vivo orthoxenopatients: one derived from a HER2+ patient and another from a patient who relapsed on trastuzumab and lapatinib-based therapy. SKTR, SKLR and SKLTR showed hyperactivation of EGFR and p-ERK1/2 and PI3KCA mutations. Dual-resistant cells (SKLTR) also showed hyperactivation of HER4 and recovered levels of p-AKT compared with mono-resistant cells. mTOR, p-mTOR and FASN expression remained stable in SKTR, SKLR and SKLTR. In vitro, anti-FASN compounds plus pertuzumab showed synergistic interactions in lapatinib- and dual- resistant cells and improved the results of pertuzumab plus trastuzumab co-treatment. FASN inhibitors combined with temsirolimus displayed the strongest synergistic interactions in resistant cells. In vivo, both orthoxenopatients showed strong response to the antitumor activity of the combination of EGCG with pertuzumab or temsirolimus, without signs of toxicity. We showed that the simultaneous blockade of FASN and HER2 pathways is effective in cells and in breast cancer models refractory to anti-HER2 therapies. PMID:26107737

  3. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    PubMed Central

    Gaudio, Carlo; Greco, Cesare; Keylani, Abdul M.; D'Agostino, Darrin C.

    2014-01-01

    This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure. PMID:25013799

  4. Spatial Analysis of HIV Positive Injection Drug Users in San Francisco, 1987 to 2005

    PubMed Central

    Martinez, Alexis N.; Mobley, Lee R.; Lorvick, Jennifer; Novak, Scott P.; Lopez, Andrea M.; Kral, Alex H.

    2014-01-01

    Spatial analyses of HIV/AIDS related outcomes are growing in popularity as a tool to understand geographic changes in the epidemic and inform the effectiveness of community-based prevention and treatment programs. The Urban Health Study was a serial, cross-sectional epidemiological study of injection drug users (IDUs) in San Francisco between 1987 and 2005 (N = 29,914). HIV testing was conducted for every participant. Participant residence was geocoded to the level of the United States Census tract for every observation in dataset. Local indicator of spatial autocorrelation (LISA) tests were used to identify univariate and bivariate Census tract clusters of HIV positive IDUs in two time periods. We further compared three tract level characteristics (% poverty, % African Americans, and % unemployment) across areas of clustered and non-clustered tracts. We identified significant spatial clustering of high numbers of HIV positive IDUs in the early period (1987–1995) and late period (1996–2005). We found significant bivariate clusters of Census tracts where HIV positive IDUs and tract level poverty were above average compared to the surrounding areas. Our data suggest that poverty, rather than race, was an important neighborhood characteristic associated with the spatial distribution of HIV in SF and its spatial diffusion over time. PMID:24722543

  5. Weighing the Consequences: Self-Disclosure of HIV-Positive Status among African American Injection Drug Users

    ERIC Educational Resources Information Center

    Valle, Maribel; Levy, Judith

    2009-01-01

    Theorists posit that personal decisions to disclose being HIV positive are made based on the perceived consequences of that disclosure. This study examines the perceived costs and benefits of self-disclosure among African American injection drug users (IDUs). A total of 80 African American IDUs were interviewed in-depth subsequent to testing HIV…

  6. Evaluation of adverse drug reactions in HIV positive patients in a tertiary care hospital

    PubMed Central

    Jha, Anshu Kumar; Gadgade, Akash; Shenoy, Ashok K.; Chowta, Mukta N.; Ramapuram, John T.

    2015-01-01

    Context: The advancement and development of new drugs and treatment strategies increase the risk of unusual Adverse Events (AEs) in HIV patients. Aims: The objective of our study was to assess the incidence, types and nature of AEs in HIV positive subjects. Settings and Design: Patients with WHO stage IV disease irrespective of the CD4 cell count, or WHO stage III disease with a CD4 cell count <350 cell/cu. Mm, or, WHO stage I or II disease with a CD4 cell count of <200 cells/cu. mm, and on prior anti-retroviral therapy for not more than six months preceding the observation date, were included in the study. After initiation of therapy, the patients were examined for the occurrence any adverse events including the type and severity, or any other abnormal laboratory findings. Causality assessment of the adverse events was done using the Naranjo's scale. Results: Out of 327 patients studied prospectively, 43 patients developed AEs. Out of these, 23 (53.5%) were males and 20 (46.5%) were females. A total of 53 (16.21%) AEs were reported. Antitubercular drugs caused the maximum AEs (28.3%) followed by zidovudine (20.7%), nevirapine (15.0%) and efavirenz (5.6%). Stavudine, ethambutol, sulfamethoxazole and trimethoprim, and atazanavir were also responsible for 3.7% of AEs individually. Causality assessment done according to the Naranjo's scale revealed that 66.04% AEs were ‘probable’ and 33.96% were ‘possible’. Conclusions: Anemia, hepatitis and dermatological adverse effects are the most common AEs. Antitubercular drugs contributed significantly for the incidence of AEs in these patients. Frequency of AEs was slightly more in males compared to females. PMID:25657900

  7. A positive cannabinoids workplace drug test following the ingestion of commercially available hemp seed oil.

    PubMed

    Struempler, R E; Nelson, G; Urry, F M

    1997-01-01

    A commercially available health food product of cold-pressed hemp seed oil ingested by one volunteer twice a day for 4 1/2 days (135 mL total). Urine specimens collected from the volunteer were subjected to standard workplace urine drug testing procedures, and the following concentrations of 11-nor-delta9- tetrahydrocannabinol carboxylic acid (9-THCA) were detected: 41 ng/mL 9-THCA at 45 h, 49 ng/mL at 69 h, and 55 ng/mL at 93 h. Ingestion was discontinued after 93 h, and the following concentrations were detected: 68 ng/mL at 108 h, 57 ng/mL at 117 h, 31 ng/mL at 126 h, and 20 ng/mL at 142 h. The first specimen that tested negative (50 ng/mL initial immunoassay test, 15 ng/mL confirmatory gas chromatographic-mass spectrometric test) was at 146 h, which was 53 h after the last hemp seed oil ingestion. Four subsequent specimens taken to 177 h were also negative. This study indicates that a workplace urine drug test positive for cannabinoids may arise from the consumption of commercially available cold-pressed hemp seed oil. PMID:9248945

  8. Personalized drug combinations to overcome trastuzumab resistance in HER2-positive breast cancer

    PubMed Central

    Vu, Thuy; Sliwkowski, Mark X.; Claret, Francois X.

    2014-01-01

    HER2-positive (HER2+) breast cancer accounts for 18%–20% of all breast cancer cases and has the second poorest prognosis among breast cancer subtypes. Trastuzumab, the first Food and Drug Administration-approved targeted therapy for breast cancer, established the era of personalized treatment for HER2+ metastatic disease. It is well tolerated and improves overall survival and time-to-disease progression; with chemotherapy, it is part of the standard of care for patients with HER2+ metastatic disease. However, many patients do not benefit from it because of resistance. Substantial research has been performed to understand the mechanism of trastuzumab resistance and develop combination strategies to overcome the resistance. In this review, we provide insight into the current pipeline of drugs used in combination with trastuzumab and the degree to which these combinations have been evaluated, especially in patients who have experienced disease progression on trastuzumab. We conclude with a discussion of the current challenges and future therapeutic approaches to trastuzumab-based combination therapy. PMID:25065528

  9. Active and latent tuberculosis among HIV-positive injecting drug users in Indonesia

    PubMed Central

    Meijerink, Hinta; Wisaksana, Rudi; Lestari, Mery; Meilana, Intan; Chaidir, Lydia; van der Ven, Andre JAM; Alisjahbana, Bachti; van Crevel, Reinout

    2015-01-01

    Introduction Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing HIV epidemic strongly driven by IDU. Methods Active tuberculosis was measured prospectively among 1900 consecutive antiretroviral treatment (ART)-naïve adult patients entering care in a clinic in West Java. Prevalence of LTBI was determined cross-sectionally in a subset of 518 ART-experienced patients using an interferon-gamma release assay. Results Patients with a history of IDU (53.1%) more often reported a history of tuberculosis treatment (34.8% vs. 21.9%, p<0.001), more often received tuberculosis treatment during follow-up (adjusted HR=1.71; 95% CI: 1.25–2.35) and more often had bacteriologically confirmed tuberculosis (OR=1.67; 95% CI: 0.94–2.96). LTBI was equally prevalent among people with and without a history of IDU (29.1 vs. 30.4%, NS). The risk estimates did not change after adjustment for CD4 cell count or ART. Conclusions HIV-positive individuals with a history of IDU in Indonesia have more active tuberculosis, with similar rates of LTBI. Within the HIV clinic, LTBI screening and isoniazid preventive therapy may be prioritized to patients with a history of IDU. PMID:25690530

  10. Construction of an Integrated Positive Youth Development Conceptual Framework for the Prevention of the Use of Psychotropic Drugs among Adolescents

    PubMed Central

    Lee, Tak Yan

    2011-01-01

    This is a theoretical paper with an aim to construct an integrated conceptual framework for the prevention of adolescents' use and abuse of psychotropic drugs. This paper first reports the subjective reasons for adolescents' drug use and abuse in Hong Kong and reviews the theoretical underpinnings. Theories of drug use and abuse, including neurological, pharmacological, genetic predisposition, psychological, and sociological theories, were reviewed. It provides a critical re-examination of crucial factors that support the construction of a conceptual framework for primary prevention of adolescents' drug use and abuse building on, with minor revision, the model of victimization and substance abuse among women presented by Logan et al. This revised model provides a comprehensive and coherent framework synthesized from theories of drug abuse. This paper then provides empirical support for integrating a positive youth development perspective in the revised model. It further explains how the 15 empirically sound constructs identified by Catalano et al. and used in a positive youth development program, the Project P.A.T.H.S., relate generally to the components of the revised model to formulate an integrated positive youth development conceptual framework for primary prevention of adolescent drug use. Theoretical and practical implications as well as limitations and recommendations are discussed. PMID:22194671

  11. The central nervous system of sea cucumbers (Echinodermata: Holothuroidea) shows positive immunostaining for a chordate glial secretion

    PubMed Central

    Mashanov, Vladimir S; Zueva, Olga R; Heinzeller, Thomas; Aschauer, Beate; Naumann, Wilfried W; Grondona, Jesus M; Cifuentes, Manuel; Garcia-Arraras, Jose E

    2009-01-01

    Background Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS), a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers. Results In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system. Conclusion Our results show that: a) the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b) the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common ancestor of all the Deuterostomia. PMID:19538733

  12. The structure of a mutant photosynthetic reaction center shows unexpected changes in main chain orientations and quinone position.

    SciTech Connect

    Pokkuluri, P. R.; Laible, P. D.; Deng, Y.-L.; Wong, T. N.; Hanson, D. K.; Schiffer, M.

    2002-05-14

    We report on the unexpected structural changes caused by substitution of acidic amino acids in the Q{sub B} binding pocket of the bacterial photosynthetic reaction center by alanines. The mutations targeted key residues L212Glu and L213Asp of this transmembrane protein-cofactor complex. The amino acid substitutions in the L212Ala-L213Ala mutant reaction center ('AA') were known to affect the delivery of protons after the light-induced generation of Q{sub B}-, which renders the AA strain incapable of photosynthetic growth. The AA structure not only revealed side chain rearrangements but also showed movement of the main chain segments that are contiguous with the mutation sites. The alanine substitutions caused an expansion of the cavity rather than its collapse. In addition, Q{sub B} is found mainly in the binding site that is proximal to the iron-ligand complex (closest to Q{sub A}) as opposed to its distal binding site (furthest from Q{sub A}) in the structure of the wild-type reaction center. The observed rearrangements in the structure of the AA reaction center establish a new balance between charged residues of an interactive network near Q{sub B}. This structurally and electrostatically altered complex forms the basis for future understanding of the structural basis for proton transfer in active reaction centers which retain the alanine substitutions but carry a distant compensatory mutation.

  13. Punitive policing and associated substance use risks among HIV-positive people in Russia who inject drugs

    PubMed Central

    Lunze, Karsten; Raj, Anita; Cheng, Debbie M.; Quinn, Emily K.; Bridden, Carly; Blokhina, Elena; Walley, Alexander Y.; Krupitsky, Evgeny; Samet, Jeffrey H.

    2014-01-01

    Introduction Drug law enforcement is part of the HIV risk environment among people who inject drugs (PWID). Punitive policing practices such as extrajudicial arrests for needle possession and police planting of drugs have been described anecdotally in Russia, but these experiences and their associations with risky drug behaviours have not been quantified. This study aims to quantify the burden of extrajudicial police arrests among a cohort of HIV-positive PWID in Russia and to explore its links to drug-related health outcomes. Methods In a cross-sectional study of 582 HIV-positive people with lifetime injection drug use (IDU) in St. Petersburg, Russia, we estimated the prevalence of self-reported extrajudicial police arrests. We used multiple logistic regression to evaluate associations between arrests and the following outcomes: overdose, recent IDU and receptive needle sharing. Findings This cohort's mean age was 29.8 years, 60.8% were male; 75.3% reported non-fatal drug overdose, 50.3% recent IDU and 47.3% receptive needle sharing. Extrajudicial arrests were reported by more than half (60.5%, 95% confidence interval [CI]: 56.5–64.5) and were associated with higher odds of non-fatal drug overdose (AOR 1.52, 95% CI: 1.02–2.25) but not with recent IDU (AOR 1.17, arrests were associated with receptive needle sharing (AOR 1.84, 95% CI: 1.09–3.09). Conclusions Extrajudicial police arrests were common among this cohort of Russian HIV-positive PWID and associated with non-fatal overdose and, among those with recent IDU, receptive needle sharing. As a part of the HIV risk environment of PWIDs, these practices might contribute to HIV transmission and overdose mortality. Further research is needed to relate these findings to the operational environment of law enforcement and to better understand how police interventions among PWIDs can improve the HIV risk environment. PMID:25014321

  14. Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

    PubMed

    Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

    2015-02-01

    A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation. PMID:25176564

  15. Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.

    PubMed

    Prasad, Dev; Chauhan, Harsh; Atef, Eman

    2014-11-01

    The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%-40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug-polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions. PMID:25196860

  16. Collagen gel droplet-embedded culture-drug sensitivity test and Ki67 expression in estrogen receptor-positive and HER2-negative breast cancer.

    PubMed

    Tozuka, Katsunori; Horiguchi, Jun; Takata, Daisuke; Rokutanda, Nana; Nagaoka, Rin; Tokiniwa, Hideaki; Kikuchi, Mami; Satou, Ayako; Takei, Hiroyuki; Takeyoshi, Izumi

    2013-01-01

    Anthracyclines and taxanes are standard anticancer drugs used in breast cancer chemotherapy. In general, the efficacy of chemotherapy is lower in patients with estrogen receptor (ER)-positive tumors compared to patients with ER-negative tumors. Although less chemosensitive, ER-positive disease includes a subset of patients who significantly benefit from adjuvant chemotherapy. The collagen gel droplet-embedded culture-drug sensitivity test (CD-DST) is an in vitro chemosensitivity test that has several advantages over conventional tests. The aim of the present study was to examine the correlation between CD-DST and the expression of Ki67, an indicator of tumor proliferation, to evaluate the efficacy of anthracyclines and taxanes in patients with ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. CD-DST was performed in 68 patients with ER-positive and HER2-negative breast cancer between August 2001 and November 2006. The specimens obtained during surgery were used for the CD-DST and immunohistological examination of Ki67 expression. Chemosensitivity to the anticancer drugs adriamycin (ADM), epirubicin (EPI), docetaxel (DOC) and paclitaxel (PTX) was estimated using CD-DST. Results obtained from the CD-DST showed the chemosensitivity to each anticancer drug to be ADM, 23.7%; EPI, 75.0%; DOC, 69.2% and PTX, 43.6%. Ki67 expression was significantly higher in the group that was sensitive to DOC compared to the group that was resistant to DOC (P=0.048) and PTX (P=0.036). In addition, a significant correlation was observed between a Ki67 labeling index (LI) of >30% and chemosensitivity to PTX. In conclusion, results obtained from CD-DST and Ki67 expression levels are able to identify a subset of patients with ER-positive and HER2-negative breast cancer who exhibit sensitivity to chemotherapy, particularly to taxane therapy. PMID:24649129

  17. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false Random drug testing requirements and identification...AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification...substance abuse program will provide for random testing for evidence of the use of...

  18. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Random drug testing requirements and identification...AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification...substance abuse program will provide for random testing for evidence of the use of...

  19. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Random drug testing requirements and identification...AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification...substance abuse program will provide for random testing for evidence of the use of...

  20. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Random drug testing requirements and identification...AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification...substance abuse program will provide for random testing for evidence of the use of...

  1. Characterization and expression of the CXCR1 and CXCR4 in miiuy croaker and evolutionary analysis shows the strong positive selection pressures imposed in mammal CXCR1.

    PubMed

    Xu, Tianjun; Zhu, Zhihuang; Sun, Yuena; Ren, Liping; Wang, Rixin

    2014-05-01

    The innate immune system can recognize non-self, danger signals, and pathogen associated molecular patterns and provides a first line of antimicrobial host defense. Therefore, it plays an instructive role and is pretty important in vertebrates. In innate immune responses, CXCRs act as the main receptors of CXC chemokines and play a vital role in host defense and inflammation. In present study, we cloned two cDNA molecules of CXCR1 and CXCR4 in Miichthys miiuy (miiuy croaker). In these two genes, we found the most highly conserved DRY motif in the second intracellular loop adjacent to the third transmembrane domain. The expressions of CXCR1 and CXCR4 showed that they were ubiquitously expressed in ten normal tissues. After infection with Vibrio anguillarum and Vibrio harveyi, the expressions of CXCRs in the immune tissues were significantly regulated in most of tissues except that of CXCR1 in the kidney after V. harveyi injection. Evolutionary analysis showed that only the ancestral lineages of CXCR4 in amphibians underwent positive selection, indicating that the ancestors of amphibians boarded the land and had to further evolve to adapt to terrestrial environments. Multiple ML methods were implemented to detect the robust positively selected candidates for sites. In total, we detected 12 and 3 positively selected sites in the subsets of current mammal and fish CXCR1 genes, and only one site under positive selection was found in mammalian CXCR4 subsets. These positively selected sites were mainly located in the extracellular domains of CXCRs. The sliding window analysis and evolution test tended to favor positive selection acting on the N-terminal domain of CXCR1, which was the critical region for ligand/receptor signaling for neutrophils and receptor-ligand interaction, indicating that the N-terminal of CXCR1 in mammals underwent more positive selection than that of fish. PMID:24333436

  2. Characterization of antibody drug conjugate positional isomers at cysteine residues by peptide mapping LC-MS analysis.

    PubMed

    Janin-Bussat, Marie-Claire; Dillenbourg, Marina; Corvaia, Nathalie; Beck, Alain; Klinguer-Hamour, Christine

    2015-02-15

    Antibody-drug conjugates (ADCs) are becoming a major class of oncology therapeutics. Because ADCs combine the monoclonal antibody specificity with the high toxicity of a drug, they can selectively kill tumor cells while minimizing toxicity to normal cells. Most of the current ADCs in clinical trials are controlled, but heterogeneous mixtures of isomers and isoforms. Very few protocols on ADC characterization at the peptide level have been published to date. Here, we report on the improvement of an ADC peptide mapping protocol to characterize the drug-loaded peptides by LC-MS analysis. These methods were developed on brentuximab vedotin (Adcetris), a commercial ADC with an average of four drugs linked to interchain cysteine residues of its antibody component. Because of the drug hydrophobicity, all the steps of this protocol including enzymatic digestion were improved to maintain the hydrophobic drug-loaded peptides in solution, allowing their unambiguous identification by LC-MS. For the first time, the payloads positional isomers observed by RP-HPLC after IdeS-digestion and reduction of the ADC were also characterized. PMID:25596378

  3. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this... Facility (FFTF); High Flux Beam Reactor (HFBR); High Flux Isotope Reactor (HFIR); K Production Reactor...

  4. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this... Facility (FFTF); High Flux Beam Reactor (HFBR); High Flux Isotope Reactor (HFIR); K Production Reactor...

  5. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this... Facility (FFTF); High Flux Beam Reactor (HFBR); High Flux Isotope Reactor (HFIR); K Production Reactor...

  6. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this... Facility (FFTF); High Flux Beam Reactor (HFBR); High Flux Isotope Reactor (HFIR); K Production Reactor...

  7. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this... Facility (FFTF); High Flux Beam Reactor (HFBR); High Flux Isotope Reactor (HFIR); K Production Reactor...

  8. A cost-utility analysis of drug treatments in patients with HBeAg-positive chronic hepatitis B in Thailand

    PubMed Central

    2014-01-01

    Background Only lamivudine has been included for patients with chronic hepatitis B (CHB) in the National List of Essential Drugs (NLED), a pharmaceutical reimbursement list in Thailand. There have also been no economic evaluation studies of CHB drug treatments conducted in Thailand yet. In order to fill this gap in policy research, the objective of this study was to compare the cost-utility of each drug therapy (Figure 1) with palliative care in patients with HBeAg-positive CHB. Methods A cost-utility analysis using an economic evaluation model was performed to compare each drug treatment for HBeAg-positive CHB patients. A Markov model was used to estimate the relevant costs and health outcomes during a lifetime horizon based on a societal perspective. Direct medical costs, direct non-medical costs, and indirect costs were included, and health outcomes were denoted in life years (LYs) and quality-adjusted life years (QALYs). The results were presented as an incremental cost effectiveness ratio (ICER) in Thai baht (THB) per LY or QALY gained. One-way sensitivity and probabilistic sensitivity analyses were applied to investigate the effects of model parameter uncertainties. Results The ICER values of providing generic lamivudine with the addition of tenofovir when drug resistance occurred, generic lamivudine with the addition of tenofovir based on the road map guideline, and tenofovir monotherapy were -14,000 (USD -467), -8,000 (USD -267) , and -5,000 (USD -167) THB per QALY gained, respectively. However, when taking into account all parameter uncertainties in the model, providing generic lamivudine with the addition of tenofovir when drug resistance occurred (78% and 75%) and tenofovir monotherapy (18% and 24%) would yield higher probabilities of being cost-effective at the societal willingness to pay thresholds of 100,000 (USD 3,333) and 300,000 (USD 10,000) THB per QALY gained in Thailand, respectively. Conclusions Based on the policy recommendations from this study, the Thai government decided to include tenofovir into the NLED in addition to generic lamivudine which is already on the list. Moreover, the results have shown that the preferred treatment regimen involves using generic lamivudine as the first-line drug with tenofovir added if drug resistance occurs in HBeAg-positive CHB patients. PMID:24731689

  9. Position Statement: Drug Holiday in Osteoporosis Treatment with Bisphosphonates in South Korea

    PubMed Central

    Lee, Seung Hun; Gong, Hyun Sik; Kim, Tae-Hee; Park, Si Young; Shin, Jung-Ho; Cho, Sun Wook

    2015-01-01

    Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from many placebo-controlled trials demonstrating its efficacy in fracture risk reduction over 3 to 5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about the adverse effects related to its long-term use, including osteonecrosis of the jaw and atypical femur fractures. Because bisphosphonates are incorporated into the skeleton and continue to exert an anti-resorptive effect for a period of time after the discontinuation of drugs, the concept of a "drug holiday" has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from anti-fracture efficacy. As randomized clinical trial evidence is not yet available on who may qualify for a drug holiday, there is considerable controversy regarding the selection of candidates for the drug holiday and monitoring during a drug holiday, both of which should be based on individual assessments of risk and benefit. This statement will provide suggestions for clinicians in South Korea on the identification of possible candidates and monitoring during a bisphosphonate drug holiday. PMID:26713307

  10. Nanoparticle mediated drug delivery of rolipram to tyrosine kinase B positive cells in the inner ear with targeting peptides and agonistic antibodies

    PubMed Central

    Glueckert, Rudolf; Pritz, Christian O.; Roy, Soumen; Dudas, Jozsef; Schrott-Fischer, Anneliese

    2015-01-01

    Aim: Systemic pharmacotherapies have limitation due to blood-labyrinth barrier, so local delivery via the round window membrane opens a path for effective treatment. Multifunctional nanoparticle (NP)-mediated cell specific drug delivery may enhance efficacy and reduce side effects. Different NPs with ligands to target TrkB receptor were tested. Distribution, uptake mechanisms, trafficking, and bioefficacy of drug release of rolipram loaded NPs were evaluated. Methods: We tested lipid based nanocapsules (LNCs), Quantum Dot, silica NPs with surface modification by peptides mimicking TrkB or TrkB activating antibodies. Bioefficacy of drug release was tested with rolipram loaded LNCs to prevent cisplatin-induced apoptosis. We established different cell culture models with SH-SY-5Y and inner ear derived cell lines and used neonatal and adult mouse explants. Uptake and trafficking was evaluated with FACS and confocal as well as transmission electron microscopy. Results: Plain NPs show some selectivity in uptake related to the in vitro system properties, carrier material, and NP size. Some peptide ligands provide enhanced targeted uptake to neuronal cells but failed to show this in cell cultures. Agonistic antibodies linked to silica NPs showed TrkB activation and enhanced binding to inner ear derived cells. Rolipram loaded LNCs proved as effective carriers to prevent cisplatin-induced apoptosis. Discussion: Most NPs with targeting ligands showed limited effects to enhance uptake. NP aggregation and unspecific binding may change uptake mechanisms and impair endocytosis by an overload of NPs. This may affect survival signaling. NPs with antibodies activate survival signaling and show effective binding to TrkB positive cells but needs further optimization for specific internalization. Bioefficiacy of rolipram release confirms LNCs as encouraging vectors for drug delivery of lipophilic agents to the inner ear with ideal release characteristics independent of endocytosis. PMID:26042029

  11. [Cardiovascular safety of non-insulin anti-diabetic drugs. Scientific position statement of SEMERGEN].

    PubMed

    Prieto, M Á; Comas Samper, J M; Escobar Cervantes, C; Gasull Molinera, V

    2014-01-01

    Diabetes increases the risk of both microvascular and macrovascular complications. Although reducing plasma glucose levels to recommended targets decreases the risk of microvascular outcomes, the effects of anti-diabetic drugs on macrovascular complications and cardiovascular death are of concern. In fact, it has been suggested that some anti-diabetic agents could even be harmful for cardiovascular outcomes. In this context, several health care regulatory agencies have established the need for performing clinical trials specifically designed to assess the cardiovascular safety of anti-diabetic drugs. The results of 2 clinical trials have recently been published that provide important information on the cardiovascular safety of dipeptidyl peptidase 4 (DPP-4) inhibitors. The aim of this document was to review the available evidence on the cardiovascular safety of non-insulin anti-diabetic drugs and provide practical recommendations on their use in this context. PMID:24882393

  12. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    SciTech Connect

    Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.; Stedman, Donald B.; Wang, Huijun; Will, Yvonne

    2013-10-15

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

  13. Hepatitis C virus (HCV) infection & risk factors for HCV positivity in injecting & non-injecting drug users attending a de-addiction centre in northern India

    PubMed Central

    Basu, Debasish; Sharma, Arun Kumar; Gupta, Sunil; Nebhinani, Naresh; Kumar, Vineet

    2015-01-01

    Background & objectives: Injecting drug use is a major route of hepatitis C virus (HCV) infection in India, but there may be other risk factors also. This study was carried out to determine the seroprevalence of anti-HCV antibody in injecting drug users (IDUs) vs. non-IDUs (NIDUs), and to study the risk estimates for HCV seropositivity in the total sample of substance users with regard to various demographic, clinical, behavioural and personality factors. Methods: The IDUs (n = 201) and NIDUs (n = 219) were assessed for demographic, clinical and behavioural information, and were rated on instruments for severity of dependence, risk behaviour and personality profiles. Anti-HCV antibody was tested by ELISA and confirmed by recombinant immunoblot assay (RIBA) test. Results: Almost one-third of the IDUs (64 of 201; 31.8%) were positive for anti-HCV antibody, as opposed to only seven (3.2%) of the NIDUs. The four risk factors strongly associated with HCV positivity in multivariate analysis were sharing syringe [Exp(B) 75.04; 95%CI 18.28-307.96; P<0.001], reuse of injection accessories (16.39; 3.51-76.92; P<0.001), blood transfusion (5.88; 1.63-21.23; P=0.007) and IDU status (3.60; 1.26-10.31; P=0.017). Other variables less strongly but significantly associated with HCV positivity were multiple sex partners, opioid dependence, risk behaviour scores, impulsivity, and lower age of onset of drug use. Interpretation & conclusions: Our study showed a high seroprevalence of anti-HCV antibody in IDUs. In the substance users, HCV positivity was significantly and independently associated with several clinical, behavioural, and personality risk factors. PMID:26458347

  14. Pyrrolidine bis-cyclic guanidines with antimicrobial activity against drug-resistant Gram-positive pathogens

    E-print Network

    Nizet, Victor

    Pyrrolidine bis-cyclic guanidines with antimicrobial activity against drug-resistant Gram chemical libraries amenable to high-throughput screening for antimicrobial activities. Here we report and bactericidal activities against the important human pathogen methicillin-resis- tant Staphylococcus aureus

  15. Ethnic hair care products may increase false positives in hair drug testing.

    PubMed

    Kidwell, David A; Smith, Frederick P; Shepherd, Arica R

    2015-12-01

    The question of why different races appear more susceptible to hair contamination by external drugs remains controversial. This research studied susceptibility of head hair to external cocaine and methamphetamine when hair products have been applied. Three different chemical classes of ethnic hair products were applied to Caucasian, Asian, and African hair. Some products increased the methamphetamine and cocaine concentrations in all hair types. A unique finding of this research is that certain ethnic hair products can replace moisture as a diffusion medium, thereby increasing the susceptibility to contamination over 100-fold compared to petroleum-based products. PMID:26338354

  16. The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells

    PubMed Central

    Lai, Y-S; Chen, J-Y; Tsai, H-J; Chen, T-Y; Hung, W-C

    2015-01-01

    Epigenetic modifying enzymes have a crucial role in the pathogenesis of acute myeloid leukemia (AML). Methylation of lysine 9 on histone H3 by the methyltransferase G9a and SUV39H1 is associated with inhibition of tumor suppressor genes. We studied the effect of G9a and SUV39H1 inhibitors on viability and differentiation of AML cells and tested the cytotoxicity induced by combination of G9a and SUV39H1 inhibitors and various epigenetic drugs. The SUV39H1 inhibitor (chaetocin) and the G9a inhibitor (UNC0638) caused cell death in AML cells at high concentrations. However, only chaetocin-induced CD11b expression and differentiation of AML cells at non-cytotoxic concentration. HL-60 and KG-1a cells were more sensitive to chaetocin than U937 cells. Long-term incubation of chaetocin led to downregulation of SUV39H1 and reduction of H3K9 tri-methylation in HL-60 and KG-1a cells. Combination of chaetocin with suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor) or JQ (a BET (bromodomain extra terminal) bromodomain inhibitor) showed synergistic cytotoxicity. Conversely, no synergism was found by combining chaetocin and UNC0638. More importantly, chaetocin-induced differentiation and combined cytotoxicity were also found in the primary cells of AML patients. Collectively, the SUV39H1 inhibitor chaetocin alone or in combination with other epigenetic drugs may be effective for the treatment of AML. PMID:25978433

  17. Please see the job posting listed below. Postdoctoral Position in the Neuroscience of Drug and Alcohol Addiction at the University of Pittsburgh.

    E-print Network

    Pillow, Jonathan

    and Alcohol Addiction at the University of Pittsburgh. Up to two postdoctoral positions are currently (particularly in the PFC) and increases susceptibility to alcoholism and drug addiction. Studies include both

  18. Positive and negative features of a computer assisted drug treatment program delivered by mentors to homeless drug users living in hostels.

    PubMed

    Neale, Joanne; Stevenson, Caral

    2014-10-01

    This paper explores positive and negative features of computer assisted therapy (CAT) delivered by mentors to homeless drug users (HDUs) living in hostels. Qualitative interviews were conducted with 30 HDUs and 15 mentors (all hostel staff) at the beginning and end of a 12-week CAT program. Findings indicate that successful delivery of the CAT relates to: 'program features' (e.g. its accessibility, flexibility, user-friendly interface); 'delivery context' (e.g. privacy, having appropriate computing equipment), 'client characteristics' (HDUs being recovery-focused and committed to using the program), and 'mentor support' (clients having personalized attention from an encouraging and sympathetic other). It is concluded that CATs can be used with HDUs but are unlikely to replace addiction therapists. Rather, they are more likely to be effective when combined with a strong therapeutic relationship. Services using CATs with HDUs need to provide staff training, support, and time to maximize the potential benefits. PMID:25037480

  19. Current cigarette smoking among HIV-positive current and former drug users: associations with individual and social characteristics

    PubMed Central

    Pacek, Lauren R.; Latkin, Carl; Crum, Rosa M.; Stuart, Elizabeth A.; Knowlton, Amy R.

    2014-01-01

    Cigarette smoking is endemic among HIV-positive populations and is related to substantial morbidity and mortality. Research has largely focused on individual-level characteristics associated with smoking, with less attention to social factors. We aimed to explore individual- and social-level characteristics associated with current cigarette smoking among people living with HIV. Data came from 358 individuals on antiretroviral therapy interviewed in a study on informal HIV caregiving, conducted in Baltimore, Maryland. Most participants (75%) were current smokers and 45% reported current illegal drug use. In adjusted logistic regression analyses, current drug use (aOR=2.90, 95% CI=1.58–5.30), 12-step program participation (aOR=1.74, 95% CI=1.02–2.97), and having a main Supporter who is a current smoker (aOR=1.93, 95% CI=1.12–3.33) were associated with current smoking. Findings suggest the importance of social-level factors in cigarette smoking among HIV seropositive drug users and have implications for developing targeted smoking cessation interventions for smokers living with HIV. PMID:24287787

  20. Effect of the position of the cyano-group of cyanopregnenolones on their drug metabolic inducing activity.

    PubMed

    Kourounakis, P N; Rekka, E; Demopoulos, V J; Retsas, S

    1991-01-01

    The effect of the position of the cyano-group of several cyanopregnenolones on the body's resistance to drugs and on drug metabolism was investigated. Female rats were pretreated with 2 alpha-, 6-, 16 alpha-, 17 alpha-cyano- or 16 alpha-cyanomethyl-pregnenolone or with pregnenolone, and the (in vivo) resistance to zoxazolamine, digitoxin and indomethacin, as well as the in vitro drug metabolism (post mitochondrial fraction) of zoxazolamine and ethylmorphine were determined. It was found that the 16-derivative was the most active in this respect, the 2- and 17-cyanopregnenolones were less active but significantly potent compared to controls, while the 6-cyano, the 16-cyanomethyl derivatives and pregnenolone were essentially inactive. These differences were explained in terms of an effective or poor fit of the steroids to their receptor. The poor performance of pregnenolone-16 alpha-acetonitrile was attributed to electronic effects. A hypothesis of some structural features of the receptor site for its interaction with the cyanopregnenolone inducers was presented. PMID:1936067

  1. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    PubMed Central

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K.; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D.; de Ángeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P.; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L.; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Lisker, Ruben; Moises, Regina S.; Menjivar, Marta; Salzano, Francisco M.; Knowler, William C.; Bortolini, M. Cátira; Hayden, Michael R.; Baier, Leslie J.; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 × 10?11) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations. PMID:20418488

  2. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids

    SciTech Connect

    Kedda, M.A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M. Univ. of Witwatersrand, Johannesburg )

    1994-06-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid [open quotes]ty-pos OCA[close quotes] individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and [open quotes]normal[close quotes] chromosomes. No haplotype showed statistically significant association with ty-pos OCA, and thus none could be used to predict the origins of the ty-pos OCA mutations. On the basis of the D15S12 results, there is evidence for multiple ty-pos OCA mutations in southern African negroids. 31 refs., 1 fig., 3 tabs.

  3. [GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators].

    PubMed

    Agabio, Roberta; Colombo, Giancarlo

    2015-01-01

    The present paper summarizes experimental and clinical data indicating the therapeutic potential of the GABAB receptor agonist, baclofen, in the treatment of alcohol use disorder (AUD) and substance use disorder (SUD). Multiple preclinical studies have demonstrated the ability of baclofen to suppress alcohol drinking (including binge- and relapse-like drinking), oral alcohol self-administration, and intravenous self-administration of cocaine, nicotine, amphetamine, methamphetamine, morphine, and heroin in rodents. Some randomized, controlled trials (RCTs) and case reports support the efficacy of baclofen in suppressing alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. Data from RCTs and open studies investigating baclofen efficacy on SUD are currently less conclusive. Interest in testing high doses of baclofen in AUD and SUD treatment has recently emerged. Preclinical research has extended the anti-addictive properties of baclofen to positive allosteric modulators of the GABAB receptor (GABAB PAMs). In light of their more favourable side effect profile (compared to baclofen), GABAB PAMs may represent a major step forward in a GABAB receptor-based pharmacotherapy of AUD and SUD. PMID:26093587

  4. Chronic obstructive pulmonary disease hospital admissions and drugs—unexpected positive associations: a retrospective general practice cohort study

    PubMed Central

    Harries, Timothy H; Seed, Paul T; Jones, Simon; Schofield, Peter; White, Patrick

    2014-01-01

    Background: Increased prescribing of inhaled long-acting anti-muscarinic (LAMA) and combined inhaled long-acting ?2-agonist and corticosteroid (LABA+ICS) drugs for the treatment of chronic obstructive pulmonary disease (COPD) has led to hopes of reduced hospital admissions from this disease. Aims: To investigate the impact of rising primary care prescribing of LAMA and LABA+ICS drugs on COPD admissions. Methods: This retrospective cohort study of general practice COPD admission and prescribing data between 2007 and 2010 comprised a representative group of 806 English general practices (population 5,264,506). Outcome measures were practice rates of COPD patient admissions and prescription costs of LAMA and LABA+ICS. General practice characteristics were based on the UK quality and outcomes framework. Results: Rates of COPD admissions remained stable from 2001 to 2010. Practice-prescribing volumes of LAMA per practice patient and LABA+ICS per practice patient increased by 61 and 26%, respectively, between 2007 and 2010. Correlation between costs of LAMA and those of LABA+ICS increased year on year, and was the highest in 2010 (Pearson’s r=0.68; 95% confidence interval (CI), 0.64–0.72). Practice COPD admission rates were positively predicted by practice-prescribing volumes of LAMA (2010: B=1.23, 95% CI, 0.61–1.85) and of LABA+ICS (2010: B=0.32, 95% CI, 0.12–0.52) when controlling for practice list size, COPD prevalence and deprivation. Conclusion: The increase in the prescribing of LAMA and LABA+ICS inhalers was not associated with the predicted fall in hospital admission rates for COPD patients. The positive correlation between high practice COPD prescribing and high practice COPD admissions was not explained. PMID:24842126

  5. This is your stream. This is your stream on drugs: Scientists' expanding research and technologies show that traces of pharmaceuticals in water may threaten aquatic health. 

    E-print Network

    Jordan, Leslie

    2010-01-01

    is not to people,? Brooks said. ?By looking at therapeutic thresh- olds for drugs, we see that these risks are much lower than others we experience in life, such as driving to work. But there are risks for the organ- isms living in these streams... their expired prescription pain-killers. In each case, traces of these drugs and other pharmachemical compounds can make their way through wastewater treatment facilities and eventually into natural water ways that supply drink- ing water for humans...

  6. Rapamycin and chloroquine: the in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy.

    PubMed

    Nalbandian, Angèle; Llewellyn, Katrina J; Nguyen, Christopher; Yazdi, Puya G; Kimonis, Virginia E

    2015-01-01

    Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can now be included as disorders that can potentially be ameliorated by rapalogs. PMID:25884947

  7. Rapamycin and Chloroquine: The In Vitro and In Vivo Effects of Autophagy-Modifying Drugs Show Promising Results in Valosin Containing Protein Multisystem Proteinopathy

    PubMed Central

    Nalbandian, Angèle; Llewellyn, Katrina J.; Nguyen, Christopher; Yazdi, Puya G.; Kimonis, Virginia E.

    2015-01-01

    Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can now be included as disorders that can potentially be ameliorated by rapalogs. PMID:25884947

  8. Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay.

    PubMed

    Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi

    2015-01-01

    The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was < 10%. Therefore, these chemicals were classified as moderate skin sensitizers in the LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE. PMID:26558466

  9. Novel Imidazoline Antimicrobial Scaffold That Inhibits DNA Replication with Activity against Mycobacteria and Drug Resistant Gram-Positive Cocci

    PubMed Central

    2015-01-01

    Bacterial antimicrobial resistance is an escalating public health threat, yet the current antimicrobial pipeline remains alarmingly depleted, making the development of new antimicrobials an urgent need. Here, we identify a novel, potent, imidazoline antimicrobial compound, SKI-356313, with bactericidal activity against Mycobacterium tuberculosis and Gram-positive cocci, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). SKI-356313 is active in murine models of Streptococcus pneumoniae and MRSA infection and is potently bactericidal for both replicating and nonreplicating M. tuberculosis. Using a combination of genetics, whole genome sequencing, and a novel target ID approach using real time imaging of core macromolecular biosynthesis, we show that SKI-356313 inhibits DNA replication and displaces the replisome from the bacterial nucleoid. These results identify a new antimicrobial scaffold with a novel mechanism of action and potential therapeutic utility against nonreplicating M. tuberculosis and antibiotic resistant Gram-positive cocci. PMID:25222597

  10. CD133-positive cancer stem cells from Colo205 human colon adenocarcinoma cell line show resistance to chemotherapy and display a specific metabolomic profile

    PubMed Central

    Vincent, Zangiacomi; Urakami, Kenichi; Maruyama, Koji; Yamaguchi, Ken; Kusuhara, Masatoshi

    2014-01-01

    During the past decade, cancer stem-like cells (CSCs) have drawn substantial interest in cancer research since they have been described as major targets to improve treatment of tumors and to prevent recurrence and metastasis. In this paper, we report on the search for CSCs within the Colo205 human adenocarcinoma cell line. We describe that CD133 (prominin) was the only reliable marker for the isolation and characterization of CSCs within a Colo205 cell population. CD133-positive cells displayed many CSC characteristics, such as tumorsphere formation ability, expression of early-stage development markers, high invasiveness, raised tumor initiation potential and resistance to cisplatin chemotherapy treatment. In vitro analyses also highlighted a specific metabolomic profile of CD133-positive cells and we concluded that the chemotherapy resistance of CSCs could be related to the quiescence of such cells associated with their reduced metabolism. Furthermore, in vivo metabolome analyses suggested that a high level of circulating glutathione molecules could also promote treatment resistance. From the perspective of metabolomics, we also discuss the controversial use of serum-free in vitro cultures for CSC enrichment prior to further phenotype characterization. PMID:25221643

  11. Various adiposity measures show similar positive associations with type 2 diabetes in Caucasians, native Hawaiians, and Japanese Americans: the multiethnic cohort.

    PubMed

    Steinbrecher, Astrid; Heak, Sreang; Morimoto, Yukiko; Grandinetti, Andrew; Kolonel, Larry N; Maskarinec, Gertraud

    2015-03-01

    The authors evaluated the association of body mass index (BMI), waist circumference (WC) and hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) with diabetes in Caucasians, Native Hawaiians, and Japanese Americans aged 45 to 75 years in the Multiethnic Cohort. Diabetes cases were obtained from self-reports and by linkages with health insurance plans. The authors estimated adjusted prevalence odds ratios (PORs) and compared the area under the receiver operating characteristic curves (AUC). All measures were positively associated with diabetes prevalence; the PORs were 1.25 to 1.64 in men and 1.52 to 1.83 in women. In all 3 ethnic groups, the AUCs in men were greater for BMI than for the other measures, whereas in women, the AUCs were greater for combined models than for BMI alone, but the differences were small and not clinically significant. It does not appear that one anthropometric measure best reflects diabetes prevalence or performs better in one ethnic group than in another. PMID:22500038

  12. ADX71441, a novel, potent and selective positive allosteric modulator of the GABAB receptor, shows efficacy in rodent models of overactive bladder

    PubMed Central

    Kalinichev, M; Palea, S; Haddouk, H; Royer-Urios, I; Guilloteau, V; Lluel, P; Schneider, M; Saporito, M; Poli, S

    2014-01-01

    Background and Purpose The GABAB receptor agonist baclofen reduces urethral resistance and detrusor overactivity in patients with spasticity. However, baclofen's side effects limit its use for the treatment of overactive bladder (OAB). Here, we tested a novel GABAB positive allosteric modulator (PAM) ADX71441 in models of OAB in mice and guinea pigs. Experimental Approach Mice were left untreated or given (p.o.) vehicle (1= CMC), ADX71441 (1, 3, 10?mg?kg?1) or oxybutynin (100?mg?kg?1; Experiment 1) or vehicle (1= CMC), baclofen (1, 3, 6?mg?kg?1) or oxybutynin (Experiment 2). Treated mice were then overhydrated with water, challenged with furosemide, before being placed into micturition chambers and monitored for urinary parameters. In anaesthetized guinea pigs, intravesical infusion of acetic acid was used to induce OAB and the effects of ADX71441 (1, 3?mg?kg?1) or baclofen (1?mg?kg?1), administered i.v., on cystometric parameters were monitored. Key Results In mice, 10?mg?kg?1 ADX71441 increased urinary latencies, reduced the number of urinary events and the total and average urinary volumes. In guinea pigs, ADX71441 (1 and 3?mg?kg?1) increased the intercontraction interval (ICI) and bladder capacity (BC), and reduced micturition frequency (MF) compared to vehicle. At 3?mg?kg?1 ADX71441 completely inhibited the micturition reflex and induced overflow incontinence in five out of 10 animals. Baclofen slightly increased ICI and BC and reduced MF. Conclusion and Implications Our findings demonstrate, for the first time, that a GABAB PAM has potential as a novel approach for the treatment of OAB. PMID:24224799

  13. Sexual Risk Behavior Associated with Co-administration of Methamphetamine and Other Drugs in a Sample of HIV-positive Men Who Have Sex with Men

    PubMed Central

    Semple, Shirley J.; Strathdee, Steffanie A.; Zians, Jim; Patterson, Thomas L.

    2011-01-01

    This study examined the association between sexual risk behavior and co-administration of methamphetamine with other drugs in a sample of 341 HIV-positive MSM. Those who reported methamphetamine co-administration in the past two months (65%) reported significantly more unprotected anal and oral sex and a greater number of casual, anonymous, and paid sex partners in this timeframe compared to men who used methamphetamine alone. Two primary patterns of co-administration were identified: 1) drug combinations motivated by sexual performance and enhancement (e.g., methamphetamine, poppers, sildenafil) and 2) “party drug” combinations (e.g., methamphetamine, GHB, ketamine). Implications for further research and possible applications to risk-reduction interventions are discussed. PMID:19219667

  14. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the state's best…

  15. Structures of substrate- and inhibitor-bound adenosine deaminase from a human malaria parasite show a dramatic conformational change and shed light on drug selectivity

    PubMed Central

    Larson, Eric T.; Deng, Wei; Krumm, Brian E.; Napuli, Alberto; Mueller, Natascha; Van Voorhis, Wesley C.; Buckner, Frederick S.; Fan, Erkang; Lauricella, Angela; DeTitta, George; Luft, Joseph; Zucker, Frank; Hol, Wim G. J.; Verlinde, Christophe L. M. J.; Merritt, Ethan A.

    2008-01-01

    Summary Plasmodium and other apicomplexan parasites are deficient in purine biosynthesis, relying instead on the salvage of purines from their host environment. Therefore interference with the purine salvage pathway is an attractive therapeutic target. The plasmodial enzyme adenosine deaminase (ADA) plays a central role in purine salvage and, unlike mammalian ADA homologs, has a further secondary role in methylthiopurine recycling. For this reason, plasmodial adenosine deaminase accepts a wider range of substrates, as it is responsible for deamination of both adenosine and 5?-methylthioadenosine. The latter substrate is not accepted by mammalian ADA homologs. The structural basis for this natural difference in specificity between plasmodial and mammalian ADA has not been well understood. We now report crystal structures of Plasmodium vivax adenosine deaminase in complex with adenosine, guanosine, and the picomolar inhibitor 2?-deoxycoformycin. These structures highlight a drastic conformational change in plasmodial ADA upon substrate-binding that has not been observed for mammalian ADA enzymes. Further, these complexes illuminate the structural basis for the differential substrate specificity and potential drug selectivity between mammalian and parasite enzymes. PMID:18602399

  16. Structures of substrate- and inhibitor-bound adenosine deaminase from a human malaria parasite show a dramatic conformational change and shed light on drug selectivity.

    PubMed

    Larson, Eric T; Deng, Wei; Krumm, Brian E; Napuli, Alberto; Mueller, Natascha; Van Voorhis, Wesley C; Buckner, Frederick S; Fan, Erkang; Lauricella, Angela; DeTitta, George; Luft, Joseph; Zucker, Frank; Hol, Wim G J; Verlinde, Christophe L M J; Merritt, Ethan A

    2008-09-12

    Plasmodium and other apicomplexan parasites are deficient in purine biosynthesis, relying instead on the salvage of purines from their host environment. Therefore, interference with the purine salvage pathway is an attractive therapeutic target. The plasmodial enzyme adenosine deaminase (ADA) plays a central role in purine salvage and, unlike mammalian ADA homologs, has a further secondary role in methylthiopurine recycling. For this reason, plasmodial ADA accepts a wider range of substrates, as it is responsible for deamination of both adenosine and 5'-methylthioadenosine. The latter substrate is not accepted by mammalian ADA homologs. The structural basis for this natural difference in specificity between plasmodial and mammalian ADA has not been well understood. We now report crystal structures of Plasmodium vivax ADA in complex with adenosine, guanosine, and the picomolar inhibitor 2'-deoxycoformycin. These structures highlight a drastic conformational change in plasmodial ADA upon substrate binding that has not been observed for mammalian ADA enzymes. Further, these complexes illuminate the structural basis for the differential substrate specificity and potential drug selectivity between mammalian and parasite enzymes. PMID:18602399

  17. Structures of Substrate-And Inhibitor-Bound Adenosine Deaminase From a Human Malaria Parasite Show a Dramatic Conformational Change And Shed Light on Drug Selectivity

    SciTech Connect

    Larson, E.T.; Deng, W.; Krumm, B.E.; Napuli, A.; Mueller, N.; Voorhis, W.C.Van; Buckner, F.S.; Fan, E.; Lauricella, A.; DeTitta, G.; Luft, J.; Zucker, F.; Hol, W.G.J.; Verlinde, C.L.M.J.; Merritt, E.A.

    2009-05-20

    Plasmodium and other apicomplexan parasites are deficient in purine biosynthesis, relying instead on the salvage of purines from their host environment. Therefore, interference with the purine salvage pathway is an attractive therapeutic target. The plasmodial enzyme adenosine deaminase (ADA) plays a central role in purine salvage and, unlike mammalian ADA homologs, has a further secondary role in methylthiopurine recycling. For this reason, plasmodial ADA accepts a wider range of substrates, as it is responsible for deamination of both adenosine and 5{prime}-methylthioadenosine. The latter substrate is not accepted by mammalian ADA homologs. The structural basis for this natural difference in specificity between plasmodial and mammalian ADA has not been well understood. We now report crystal structures of Plasmodium vivax ADA in complex with adenosine, guanosine, and the picomolar inhibitor 2{prime}-deoxycoformycin. These structures highlight a drastic conformational change in plasmodial ADA upon substrate binding that has not been observed for mammalian ADA enzymes. Further, these complexes illuminate the structural basis for the differential substrate specificity and potential drug selectivity between mammalian and parasite enzymes.

  18. Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.

    PubMed

    Fischer, Ute; Forster, Michael; Rinaldi, Anna; Risch, Thomas; Sungalee, Stéphanie; Warnatz, Hans-Jörg; Bornhauser, Beat; Gombert, Michael; Kratsch, Christina; Stütz, Adrian M; Sultan, Marc; Tchinda, Joelle; Worth, Catherine L; Amstislavskiy, Vyacheslav; Badarinarayan, Nandini; Baruchel, André; Bartram, Thies; Basso, Giuseppe; Canpolat, Cengiz; Cario, Gunnar; Cavé, Hélène; Dakaj, Dardane; Delorenzi, Mauro; Dobay, Maria Pamela; Eckert, Cornelia; Ellinghaus, Eva; Eugster, Sabrina; Frismantas, Viktoras; Ginzel, Sebastian; Haas, Oskar A; Heidenreich, Olaf; Hemmrich-Stanisak, Georg; Hezaveh, Kebria; Höll, Jessica I; Hornhardt, Sabine; Husemann, Peter; Kachroo, Priyadarshini; Kratz, Christian P; Kronnie, Geertruy Te; Marovca, Blerim; Niggli, Felix; McHardy, Alice C; Moorman, Anthony V; Panzer-Grümayer, Renate; Petersen, Britt S; Raeder, Benjamin; Ralser, Meryem; Rosenstiel, Philip; Schäfer, Daniel; Schrappe, Martin; Schreiber, Stefan; Schütte, Moritz; Stade, Björn; Thiele, Ralf; Weid, Nicolas von der; Vora, Ajay; Zaliova, Marketa; Zhang, Langhui; Zichner, Thomas; Zimmermann, Martin; Lehrach, Hans; Borkhardt, Arndt; Bourquin, Jean-Pierre; Franke, Andre; Korbel, Jan O; Stanulla, Martin; Yaspo, Marie-Laure

    2015-09-01

    TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease. PMID:26214592

  19. A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

    PubMed Central

    Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

    2014-01-01

    Background We previously found that a very low geno2pheno false positive rate (FPR ?2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ?2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. Methods The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ?2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ?150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Results Overall, at therapy start, 27% of patients had FPR ?10 (6%, FPR ?2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ?2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p?=?0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ?2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p?=?0.003) and to achieve virological success (0.50 [0.26–0.94], p?=?0.031) than those with pre-HAART FPR >60%. Conclusions Beyond the genotypically-inferred tropism determination, FPR ?2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability. PMID:25153969

  20. 1. Show the synthesis of prontosil. Show the starting

    E-print Network

    Gates, Kent. S.

    to prepare the other five derivatives shown below. 4. Show the synthesis of the sulfa drug on the right. Show in the synthetic route. SH2N O O NH2 Sulfa drug SH2N O O H N ON Sulfamethoxazole (Bactrim/Septra) SH2N O O H N N N answer will appear in every undergraduate organic textbook). N N 5. The (imaginary) drug shown below

  1. Prevalence of and Risk Factors for Oral Human Papillomavirus Infection among HIV-Positive and HIV-Negative People Who Inject Drugs

    PubMed Central

    Robbins, Hilary A.; Fennell, Christina E.; Gillison, Maura; Xiao, Weihong; Guo, Yingshi; Wentz, Alicia; Kirk, Gregory D.; Mehta, Shruti H.; D’Souza, Gypsyamber

    2015-01-01

    Background Human papillomavirus (HPV) causes most oropharyngeal cancers in the United States. Oral HPV prevalence is associated with immunosuppression, and drug use can be immunosuppressive, but the epidemiology of oral HPV among people who use drugs is not well described. Methods We enrolled men and women with a current or prior history of injection drug use in this cross-sectional sub-study within the AIDS Linked to the Intravenous Experience (ALIVE) cohort. We tested oral rinse samples for 37 types of HPV DNA and collected self-reported risk factor information. We compared oral HPV prevalence across categories using chi-squared statistics and multivariable logistic regression. Results Among 199 subjects, 32% were HIV-positive (median CD4 count 384 cells/?L), 90% were Black, 56% had less than a high school education, 17% had recently used injection drugs, and the median age was 54 years. Most had performed oral sex (82%) but had fewer than 5 lifetime partners (58%). The prevalence of any oral HPV was 29%, and of any oncogenic oral HPV was 13%. Oral HPV prevalence was high among both heterosexual men (30%) and women (20%). After adjustment, odds of oral HPV were increased among HIV-positive individuals with a low CD4 count (<350 cells/?l, aOR = 2.7, 95%CI = 1.2–6.4, vs. HIV-negative individuals), but not among HIV-positive individuals with a higher CD4 cell count. Odds were also elevated for those who had recently performed oral sex on a woman (aOR = 2.2, 95%CI = 1.01–4.6) and, even after this adjustment, among bisexual/lesbian females (aOR = 5.6, 95%CI = 1.4–23, vs. heterosexual females). Oral HPV prevalence was not associated with vaginal sex, performing oral sex on a man, or recent drug use. Conclusions Recent drug use was not associated with oral HPV prevalence in our study. However, despite modest numbers of sexual partners, the prevalence of oral HPV among this largely Black population with lower socioeconomic status was high. PMID:26600158

  2. Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.

    PubMed

    Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Romano, Simone; Fusco, Letizia; Cavaletti, Guido; Melcangi, Roberto Cosimo

    2015-02-01

    Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3?-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3?-diol, 3?-diol and 17?-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'. PMID:24717976

  3. Social-structural contexts of needle and syringe sharing behaviours of HIV-positive injecting drug users in Manipur, India: a mixed methods investigation

    PubMed Central

    2011-01-01

    Background Few investigations have assessed risk behaviours and social-structural contexts of risk among injecting drug users (IDUs) in Northeast India, where injecting drug use is the major route of HIV transmission. Investigations of risk environments are needed to inform development of effective risk reduction interventions. Methods This mixed methods study of HIV-positive IDUs in Manipur included a structured survey (n = 75), two focus groups (n = 17), seven in-depth interviews, and two key informant interviews. Results One-third of survey participants reported having shared a needle/syringe in the past 30 days; among these, all the men and about one-third of the women did so with persons of unknown HIV serostatus. A variety of social-structural contextual factors influenced individual risk behaviours: barriers to carrying sterile needles/syringes due to fear of harassment by police and "anti-drug" organizations; lack of sterile needles/syringes in drug dealers' locales; limited access to pharmacy-sold needles/syringes; inadequate coverage by needle and syringe programmes (NSPs); non-availability of sterile needles/syringes in prisons; and withdrawal symptoms superseding concern for health. Some HIV-positive IDUs who shared needles/syringes reported adopting risk reduction strategies: being the 'last receiver' of needles/syringes and not a 'giver;' sharing only with other IDUs they knew to be HIV-positive; and, when a 'giver,' asking other IDUs to wash used needles/syringes with bleach before using. Conclusions Effective HIV prevention and care programmes for IDUs in Northeast India may hinge on several enabling contexts: supportive government policy on harm reduction programmes, including in prisons; an end to harassment by the police, army, and anti-drug groups, with education of these entities regarding harm reduction, creation of partnerships with the public health sector, and accountability to government policies that protect IDUs' human rights; adequate and sustained funding for NSPs to cover all IDU populations, including prisoners; and non-discriminatory access by IDUs to affordable needles/syringes in pharmacies. PMID:21569478

  4. Differential Predictors of Medication Adherence in HIV: Findings from a Sample of African American and Caucasian HIV-Positive Drug-Using Adults

    PubMed Central

    Moizel, Jennifer; Panos, Stella E.; Patel, Sapna M.; Byrd, Desiree A.; Myers, Hector F.; Wyatt, Gail E.; Hinkin, Charles H.

    2012-01-01

    Abstract Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/AIDS disease progression and mortality. In a sample of 181 African American (n=144) and Caucasian (n=37) HIV-positive drug-using individuals [age (M=42.31; SD=6.6) education (M=13.41; SD=2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002–2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use). PMID:22889235

  5. Target-Independent Prediction of Drug Synergies Using Only Drug Lipophilicity

    PubMed Central

    2015-01-01

    Physicochemical properties of compounds have been instrumental in selecting lead compounds with increased drug-likeness. However, the relationship between physicochemical properties of constituent drugs and the tendency to exhibit drug interaction has not been systematically studied. We assembled physicochemical descriptors for a set of antifungal compounds (“drugs”) previously examined for interaction. Analyzing the relationship between molecular weight, lipophilicity, H-bond donor, and H-bond acceptor values for drugs and their propensity to show pairwise antifungal drug synergy, we found that combinations of two lipophilic drugs had a greater tendency to show drug synergy. We developed a more refined decision tree model that successfully predicted drug synergy in stringent cross-validation tests based on only lipophilicity of drugs. Our predictions achieved a precision of 63% and allowed successful prediction for 58% of synergistic drug pairs, suggesting that this phenomenon can extend our understanding for a substantial fraction of synergistic drug interactions. We also generated and analyzed a large-scale synergistic human toxicity network, in which we observed that combinations of lipophilic compounds show a tendency for increased toxicity. Thus, lipophilicity, a simple and easily determined molecular descriptor, is a powerful predictor of drug synergy. It is well established that lipophilic compounds (i) are promiscuous, having many targets in the cell, and (ii) often penetrate into the cell via the cellular membrane by passive diffusion. We discuss the positive relationship between drug lipophilicity and drug synergy in the context of potential drug synergy mechanisms. PMID:25026390

  6. Antiretroviral Drug-Related Liver Mortality Among HIV-Positive Persons in the Absence of Hepatitis B or C Virus Coinfection: The Data Collection on Adverse Events of Anti-HIV Drugs Study

    PubMed Central

    Kovari, Helen; Sabin, Caroline A.; Ledergerber, Bruno; Ryom, Lene; Worm, Signe W.; Smith, Colette; Phillips, Andrew; Reiss, Peter; Fontas, Eric; Petoumenos, Kathy; De Wit, Stéphane; Morlat, Philippe; Lundgren, Jens D.; Weber, Rainer

    2013-01-01

    Background.?Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)–positive persons since the widespread use of combination antiretroviral treatment (cART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other causes. Prolonged exposure to some antiretroviral drugs might increase hepatic mortality. Methods.?All patients in the Data Collection on Adverse Events of Anti-HIV Drugs study without HCV or HBV coinfection were prospectively followed from date of entry until death or last follow-up. In patients with liver-related death, clinical charts were reviewed using a structured questionnaire. Results.?We followed 22 910 participants without hepatitis virus coinfection for 114 478 person-years. There were 12 liver-related deaths (incidence, 0.10/1000 person-years); 7 due to severe alcohol use and 5 due to established ART-related toxicity. The rate of ART-related deaths in treatment-experienced persons was 0.04/1000 person-years (95% confidence interval, .01, .10). Conclusions.?We found a low incidence of liver-related deaths in HIV-infected persons without HCV or HBV coinfection. Liver-related mortality because of ART-related toxicity was rare. PMID:23090925

  7. Evaluation of Idaho's DARE "Drug Abuse Resistance Education" Projects.

    ERIC Educational Resources Information Center

    Silva, Roberta K.

    The DARE (Drug Abuse Resistance Education) program teaches students decision-making skills, shows them how to resist peer pressure to experiment with drugs and alcohol, and provides positive alternatives to drug use. This report looks at one state's DARE programs. Included are an overview of the implementation process, a program appraisal with…

  8. Differential Modulation of Thresholds for Intracranial Self-Stimulation by mGlu5 Positive and Negative Allosteric Modulators: Implications for Effects on Drug Self-Administration

    PubMed Central

    Cleva, Richard M.; Watterson, Lucas R.; Johnson, Meagan A.; Olive, M. Foster

    2011-01-01

    Pharmacological manipulation of the type 5 metabotropic glutamate (mGlu5) receptor alters various addiction related behaviors such as drug self-administration and the extinction and reinstatement of drug-seeking behavior. However, the effects of pharmacological modulation of mGlu5 receptors on brain reward function have not been widely investigated. We examined the effects of acute administration of positive and negative allosteric modulators (PAMs and NAMs, respectively) on brain reward function by assessing thresholds for intracranial self-stimulation (ICSS). In addition, when acute effects were observed, we examined changes in ICSS thresholds following repeated administration. Male Sprague-Dawley rats were implanted with bipolar electrodes into the medial forebrain bundle and trained to respond for ICSS, followed by assessment of effects of mGlu5 ligands on ICSS thresholds using a discrete trials current–intensity threshold determination procedure. Acute administration of the selective mGlu5 NAMs MTEP (0, 0.3, 1, or 3?mg/kg) and fenobam (0, 3, 10, or 30?mg/kg) dose-dependently increased ICSS thresholds (?70% at the highest dose tested), suggesting a deficit in brain reward function. Acute administration of the mGlu5 PAMs CDPPB (0, 10, 30, and 60?mg/kg) or ADX47273 (0, 10, 30, and 60?mg/kg) was without effect at any dose tested. When administered once daily for five consecutive days, the development of tolerance to the ability of threshold-elevating doses of MTEP and fenobam to increase ICSS thresholds was observed. We conclude that mGlu5 PAMs and NAMs differentially affect brain reward function, and that tolerance to the ability of mGlu5 NAMs to reduce brain reward function develops with repeated administration. These brain reward deficits should be taken into consideration when interpreting acute effects of mGlu5 NAMs on drug self-administration, and repeated administration of these ligands may be an effective method to reduce these deficits. PMID:22232603

  9. Clinical Efficacy of a West African Sorghum bicolor-Based Traditional Herbal Preparation Jobelyn Shows Increased Hemoglobin and CD4+ T-Lymphocyte Counts in HIV-Positive Patients

    PubMed Central

    Ayuba, Godwin I.; Jensen, Gitte S.; Benson, Kathleen F.; Okubena, Ademola M.

    2014-01-01

    Abstract Objectives: The purpose of this study was to evaluate a traditional herbal preparation, Jobelyn,® for its effects on anemia and CD4+ T-cell counts in human immunodeficiency virus–positive (HIV+) patients in Nigeria. Design: An open-label pilot study involving 10 confirmed (HIV+) patients who were not receiving antiretroviral therapy (ARVT) was performed, in which the patients consumed Jobelyn for 8 weeks, at a dose of 500?mg twice daily. The pilot study was followed by a controlled trial involving 51 patients, all confirmed HIV+, where the patients with CD4+ T-cell counts below 350 cells/?L were receiving ARVT. The eight patients with baseline CD4+ T-cell counts above 350 cells/?L received Jobelyn. The remaining patients who all received ARVT were randomized to ARVT alone versus ARVT+Jobelyn for 12 weeks. Results: Patients receiving ARVT showed a statistically significant improvement in their CD4+ T-cell counts across the 12-week study period (p<0.01). Patients receiving ARVT+Jobelyn showed a faster improvement, reaching a high level of statistical significance compared to baseline already at 6 weeks (p<0.001), and remained highly significant at 12 weeks (p<0.001). Conclusions: This is the first controlled study conducted to evaluate efficacy of Jobelyn on immune status in HIV+ patients. The data suggest that consumption of Jobelyn contributed to improved hemoglobin levels and increased CD4+ T-cell counts in Nigerian HIV+ patients. Further studies are needed to examine similar effects in other populations, and to elaborate on the underlying mechanisms, specifically, whether the consumption of Jobelyn supported multiple aspects of bone marrow function. PMID:24283768

  10. Content uniformity of potent drugs in tablets.

    PubMed

    Orr, N A; Sallam, E A

    1978-12-01

    The type of distribution of low dosage drugs that occurs in batches of commercially available tablets has been examined. The uniformity of content of ethinyloestradiol tablets 10 micrograms B.P. from different sources, assessed by single tablet assay showed that three batches exhibited some positive skewness and one marked positive skewness. At the high level of dilution required, the mixing theory indicates that particles of drug must be very fine if acceptable content uniformity is to be obtained. Cohesion of particles impairs the efficiency of the mixing process. It is shown theoretically that unless the drug is dispersed into its component particles the shape of the distribution curve for the content of drug per tablet, in a batch of tablets, will be positively skewed. The relation between the tensile strength of the powdered drug and the degree of skewness of the drug content is also discussed. A positively skewed distribution for tablets containing a small amount of potent drug is unacceptable because this can lead to the presence of relatively large doses of drug in a single tablet. Where one unexpectedly high result occurs in the quality control of the content uniformity of tablets containing potent drugs it is suggested that sufficient single tablet assays be performed to allow the shape of the distribution curve to be assessed. A test for skewness should be included in compendial standards. PMID:32236

  11. Back to the basics: identifying positive youth development as the theoretical framework for a youth drug prevention program in rural Saskatchewan, Canada amidst a program evaluation

    PubMed Central

    2013-01-01

    Background Despite endorsement by the Saskatchewan government to apply empirically-based approaches to youth drug prevention services in the province, programs are sometimes delivered prior to the establishment of evidence-informed goals and objectives. This paper shares the 'preptory’ outcomes of our team’s program evaluation of the Prince Albert Parkland Health Region Mental Health and Addiction Services’ Outreach Worker Service (OWS) in eight rural, community schools three years following its implementation. Before our independent evaluation team could assess whether expectations of the OWS were being met, we had to assist with establishing its overarching program goals and objectives and 'at-risk’ student population, alongside its alliance with an empirically-informed theoretical framework. Methods A mixed-methods approach was applied, beginning with in-depth focus groups with the OWS staff to identify the program’s goals and objectives and targeted student population. These were supplemented with OWS and school administrator interviews and focus groups with school staff. Alignment with a theoretical focus was determined though a review of the OWS’s work to date and explored in focus groups between our evaluation team and the OWS staff and validated with the school staff and OWS and school administration. Results With improved understanding of the OWS’s goals and objectives, our evaluation team and the OWS staff aligned the program with the Positive Youth Development theoretical evidence-base, emphasizing the program’s universality, systems focus, strength base, and promotion of assets. Together we also gained clarity about the OWS’s definition of and engagement with its 'at-risk’ student population. Conclusions It is important to draw on expert knowledge to develop youth drug prevention programming, but attention must also be paid to aligning professional health care services with a theoretically informed evidence-base for evaluation purposes. If time does not permit for the establishment of evidence-informed goals and objectives at the start-up of a program, obtaining insight and expertise from program personnel and school staff and administrators can bring the program to a point where this can still be achieved and theoretical linkages made after a program has been implemented. This is a necessary foundation for measuring an intervention’s success. PMID:24148918

  12. Heterotropic Activation of the Midazolam Hydroxylase Activity of CYP3A by a Positive Allosteric Modulator of mGlu5: In Vitro to In Vivo Translation and Potential Impact on Clinically Relevant Drug-Drug Interactions

    PubMed Central

    Blobaum, Anna L.; Bridges, Thomas M.; Byers, Frank W.; Turlington, Mark L.; Mattmann, Margrith E.; Morrison, Ryan D.; Mackie, Claire; Lavreysen, Hilde; Bartolomé, José M.; MacDonald, Gregor J.; Steckler, Thomas; Jones, Carrie K.; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Stauffer, Shaun R.

    2013-01-01

    Allosteric modulation of G protein-coupled receptors has gained considerable attention in the drug discovery arena because it opens avenues to achieve greater selectivity over orthosteric ligands. We recently identified a series of positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) for the treatment of schizophrenia that exhibited robust heterotropic activation of CYP3A4 enzymatic activity. The prototypical compound from this series, 5-(4-fluorobenzyl)-2-((3-fluorophenoxy)methyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (VU0448187), was found to activate CYP3A4 to >100% of its baseline intrinsic midazolam (MDZ) hydroxylase activity in vitro; activation was CYP3A substrate specific and mGlu5 PAM dependent. Additional studies revealed the concentration-dependence of CYP3A activation by VU0448187 in multispecies hepatic and intestinal microsomes and hepatocytes, as well as a diminished effect observed in the presence of ketoconazole. Kinetic analyses of the effect of VU0448187 on MDZ metabolism in recombinant P450 or human liver microsomes resulted in a significant increase in Vmax (minimal change in Km) and required the presence of cytochrome b5. The atypical kinetics translated in vivo, as rats receiving an intraperitoneal administration of VU0448187 prior to MDZ treatment demonstrated a significant increase in circulating 1- and 4-hydroxy- midazolam (1-OH-MDZ, 4-OH-MDZ) levels compared with rats administered MDZ alone. The discovery of a potent substrate-selective activator of rodent CYP3A with an in vitro to in vivo translation serves to illuminate the impact of increasing intrinsic enzymatic activity of hepatic and extrahepatic CYP3A in rodents, and presents the basis to build models capable of framing the clinical relevance of substrate-dependent heterotropic activation. PMID:24003250

  13. Fluency of pharmaceutical drug names predicts perceived hazardousness, assumed side effects and willingness to buy.

    PubMed

    Dohle, Simone; Siegrist, Michael

    2014-10-01

    The impact of pharmaceutical drug names on people's evaluations and behavioural intentions is still uncertain. According to the representativeness heuristic, evaluations should be more positive for complex drug names; in contrast, fluency theory suggests that evaluations should be more positive for simple drug names. Results of three experimental studies showed that complex drug names were perceived as more hazardous than simple drug names and negatively influenced willingness to buy. The results are of particular importance given the fact that there is a worldwide trend to make more drugs available for self-medication. PMID:23740259

  14. A Study of Therapeutic Attitudes Towards Working With Drug Abusers: Reliability and Validity of the Japanese Version of the Drug and Drug Problems Perception Questionnaire.

    PubMed

    Takano, Ayumi; Kawakami, Norito; Miyamoto, Yuki; Matsumoto, Toshihiko

    2015-10-01

    Positive therapeutic attitudes from healthcare professionals are important when providing medical services. The Drug and Drug Problems Perception Questionnaire (DDPPQ) measures healthcare professionals' attitudes towards working with drug abusers. We developed a Japanese version (J-DDPPQ) and examined its reliability and validity among Japanese nurses. The J-DDPPQ showed good internal consistency (Cronbach's alpha=0.92). Using exploratory factor analysis, the five-factor structure was found to be identical to the original structure. Construct validity was supported by significant positive correlations with experience working with drug abusers, a high level of knowledge and skills, receiving education and training, and optimistic perception about people with drug dependence. The results show that the J-DDPPQ has acceptable reliability and validity and will contribute to investigating the effect of education and training on drug abuse. PMID:26397433

  15. Positive Proof.

    ERIC Educational Resources Information Center

    Auty, Geoffrey

    1988-01-01

    Presents experiments which show that in electrostatics there are logical reasons for describing charged materials as positive or negative. Indicates that static and current electricity are not separate areas of physics. Diagrams of experiments and circuits are included. (RT)

  16. Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

    PubMed Central

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L.; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M.; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 ?g/ml respectively; minimum effective concentration: ? 0.78 ?g/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 ?g/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 ?g/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. PMID:25897961

  17. Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

    PubMed

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 ?g/ml respectively; minimum effective concentration: ? 0.78 ?g/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 ?g/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 ?g/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. PMID:25897961

  18. Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

    TOXLINE Toxicology Bibliographic Information

    Rajamuthiah R; Fuchs BB; Conery AL; Kim W; Jayamani E; Kwon B; Ausubel FM; Mylonakis E

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 ?g/ml respectively; minimum effective concentration: ? 0.78 ?g/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 ?g/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 ?g/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.

  19. STAR Trial Shows Lower Toxicities from Raloxifene

    Cancer.gov

    Initial results in 2006 of the NCI-sponsored Study of Tamoxifen and Raloxifene (STAR) showed that a common osteoporosis drug, raloxifene, prevented breast cancer to the same degree, but with fewer serious side-effects, than the drug tamoxifen that had bee

  20. TBM shows superior sample size estimates over traditional clinical measures; fewer patients are needed for evaluating new drugs. A 24-month trial provides most power, except when patient attrition exceeds 15-16%/year, in which case a 12-month trial is opt

    E-print Network

    Thompson, Paul

    TBM shows superior sample size estimates over traditional clinical measures; fewer patients, automated brain mapping methods, such as tensor-based morphometry (TBM) of structural MRI, have outperformed estimates for drug trials. In the largest TBM study to date, we studied how sample size estimates

  1. Acceptability of Global Positioning System technology to survey injecting drug users’ movements and social interactions: a pilot study from San Francisco, USA

    PubMed Central

    Mirzazadeh, A; Grasso, M; Johnson, K; Briceno, A; Navadeh, S; McFarland, W; Page, K

    2015-01-01

    Background Despite potential applications for improving health services using GPS technology, little is known about ethical concerns, acceptability, and logistical barriers for their use, particularly among marginalized groups. Objectives We garnered the insights of people who inject drug (PWID) in San Francisco on these topics. Methods PWID were enrolled through street-outreach (n=20) and an ongoing study (n=4) for 4 focus group discussions. Participants also completed a self-administered questionnaire on demographic characteristics and their numbers and types of interactions with other PWID. Results Median age was 30.5 years, majorities were male (83.3%) and white (68.2%). Most interacted with other PWID for eating meals and purchasing drugs over the last week; fewer reported interactions such as sexual contact, drug treatment, or work. Participants identified several concerns about carrying GPS devices, including what authorities might do with the data, that other PWID and dealers may suspect them as informants, and adherence to carrying and use. Most felt concerns were surmountable with detailed informed consent on the purpose of the study and practical ways to carry, charge, and hide devices. Conclusions PWID felt data collection on their movements and social interactions with other PWID using GPS can be acceptable with addressing specific concerns. The technology is now in hand to greatly expand the ability to monitor health conditions with respect to the environment and improve the location of prevention, care, and treatment facilities to serve hard to reach, mobile, and hidden populations. PMID:24990173

  2. Club Drugs

    MedlinePLUS

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  3. Position of chromatographic techniques in screening for detection of drugs or poisons in clinical and forensic toxicology and/or doping control.

    PubMed

    Maurer, Hans H

    2004-01-01

    This paper reviews chromatographic screening procedures for simultaneous detection of several drug classes relevant to clinical and forensic toxicology or doping control in urine or blood using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with a diode-array detector (LC-DAD) or a mass spectrometer (LC-MS). The pros and cons of the different techniques and procedures are discussed leading to the following conclusions and perspectives. GC-MS, especially in the electron ionization full-scan mode, is still the method of choice for comprehensive screening providing best separation power, specificity and universality, although requiring derivatization. LC-DAD is also often used for screening, but its separation power and its specificity are still inferior to those of GC-MS. Finally, LC-MS has shown to be an ideal supplement, especially for the detection of more polar, thermolabile and/or low-dose drugs, especially in blood plasma. It may become the gold standard in clinical and forensic toxicology and doping control if, at a later date, the costs of the apparatus will be markedly reduced, the current disadvantages like irreproducibility of fragmentation, reduction of ionization by matrix, etc. will be overcome, and finally if one of the increasing number of quite different techniques will become the apparatus standard. PMID:15576292

  4. Drug Usage and Attitude Toward Drugs Among College Students

    ERIC Educational Resources Information Center

    Cross, Herbert J.; Keir, Richard G.

    1971-01-01

    Results of the data presented suggest that there is considerable experimentation among college students with illegal drugs, especially marijuana. Their attitudes toward other drugs still seems cautious. Marijuana, however, seems-to be accepted and generally positively evaluated. (Author)

  5. The 3-metros study of drugs and crime in South Africa: findings and policy implications.

    PubMed

    Parry, Charles D; Plüddemann, Andreas; Louw, Antoinette; Leggett, Ted

    2004-01-01

    This study examined the drug-crime nexus by investigating the prevalence of recent drug use among persons arrested by the police. Data were gathered during August/September 2000 from 1050 adult arrestees in eight police stations in Cape Town, Durban, and Johannesburg (South Africa). Measures included urinalysis results for cannabis, methaqualone (Mandrax), opiates, cocaine, amphetamines, and benzodizepines, and a questionnaire designed to assess socioeconomic and demographic backgrounds of arrestees, history of prior arrests and imprisonment, current arrest information, profile of substance use, etc. Results of the study show high levels of drug use among arrestees, with 45% testing positive for at least one drug (mainly cannabis and Mandrax). A greater proportion of arrestees in Cape Town tested positive for drugs than in the other sites. Data were also analyzed in terms of gender, age, race, location (site and police station), and offense category. Persons arrested on charges of housebreaking or for drugs/alcohol offenses were particularly likely to test positive for drugs. Drug positive arrestees were more likely to have had a prior arrest. Among the conclusions of the study are that 1) strategies to reduce drug use and drug related crime must be area specific, 2) particular attention needs to focus on young offenders, 3) police need to be trained to recognize particular symptoms and to establish protocols on handling arrestees under the influence of drugs, and 4) diversion to treatment of drug using offenders deserves more consideration. PMID:15083560

  6. The Art Show

    ERIC Educational Resources Information Center

    Scolarici, Alicia

    2004-01-01

    This article describes what once was thought to be impossible--a formal art show extravaganza at an elementary school with 1,000 students, a Department of Defense Dependent School (DODDS) located overseas, on RAF Lakenheath, England. The dream of this this event involved the transformation of the school cafeteria into an elegant art show

  7. Drug Arrests and Injection Drug Deterrence

    PubMed Central

    Pouget, Enrique R.; Chatterjee, Sudip; Cleland, Charles M.; Tempalski, Barbara; Brady, Joanne E.; Cooper, Hannah L. F.

    2011-01-01

    Objectives. We tested the hypothesis that higher rates of previous hard drug–related arrests predict lower rates of injection drug use. Methods. We analyzed drug-related arrest data from the Federal Bureau of Investigation's Uniform Crime Reporting Program for 93 large US metropolitan statistical areas in 1992 to 2002 to predict previously published annual estimates of the number of injection drug users (IDUs) per 10 000 population. Results. In linear mixed-effects regression, hard drug–related arrest rates were positively associated (parameter = +1.59; SE = 0.57) with the population rate of IDUs in 1992 and were not associated with change in the IDU rate over time (parameter = ?0.15; SE = 0.39). Conclusions. Deterrence-based approaches to reducing drug use seem not to reduce IDU prevalence. Alternative approaches such as harm reduction, which prevents HIV transmission and increases referrals to treatment, may be a better foundation for policy. PMID:21164088

  8. Making drugs accessible.

    PubMed

    1999-01-01

    Making drugs accessible for common HIV-associated illnesses in West Africa is discussed. HIV-positive people in Ouagadougou, Burkina Faso, could not afford drugs for treating their illnesses; thus, volunteers from La Bergerie-FUC, a Christian organization, have established a day care center for HIV-positive people. A French church supplies the drugs; oral rehydration salts are provided through the Ministry of Health. Since the organization did not have enough drugs to meet the needs of all its patients, two strategies were developed to improve its drug supply. The first strategy was to raise money to buy drugs through the support of a local NGO, the Initiative Privee et Communautaire de lutte contre le SIDA (IPC). IPC initially refused to support them, but, eventually agreed to fund drug purchasing as a pilot project. The second strategy was to look at ways of reducing the cost of drugs, which resulted in a list of essential drugs for HIV-associated infections. The list was approved by Care and Support Committee of the national AIDS program for use by other organizations. The organizations have created a national network to improve the delivery of community-based care and support services in Burkina Faso. Recently, the national AIDS program has asked this network to help them change the national essential drugs list to include essential drugs for treating common HIV-associated infections. PMID:12349193

  9. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  10. Pharmacokinetics and bactericidal rates of daptomycin and vancomycin in intravenous drug abusers being treated for gram-positive endocarditis and bacteremia.

    PubMed

    Rybak, M J; Bailey, E M; Lamp, K C; Kaatz, G W

    1992-05-01

    The pharmacokinetics and bactericidal killing rates (BR) of daptomycin (D) and vancomycin (V) in 12 intravenous drug abusers (6 treated with daptomycin and 6 treated with vancomycin) were evaluated. Pharmacokinetic parameters were determined from multiple serum samples drawn at steady state over a 12-h dosing interval after intravenous infusions of 3 mg of D per kg of body weight and 1,000 mg of V. The BRs were determined from the 1- and 6-h serum samples by using four isolates of Staphylococcus aureus (three methicillin susceptible and one methicillin resistant) obtained from the patients enrolled in the study. Peak serum daptomycin concentrations were lower and volumes of distribution were higher than reported in healthy volunteers. Although not statistically different, D clearance was 22% higher than reported in healthy volunteers. V pharmacokinetics were similar to those reported in previous studies. Daptomycin's BRs, although comparable to those of V in patients' serum, were significantly decreased compared with those found in broth. This may be related to the high degree of protein binding of D (93% versus 50% for V). Conversely, the BRs of V in serum were significantly greater than those in broth. The BRs of D and V in broth were greater when killing curves were performed with test strains in logarithmic versus stationary-phase growth. The ability to kill organisms in stationary phase may be an important factor in determining the performance of an antibiotic in deep-seated infections such as endocarditis.3+ PMID:1324637

  11. Figure 2: Sample of single object tracking trial from one subject showing horizontal gaze-position (green), finger tap selection (blue) and motion path of tracked object (red). This participants uses discrete eye-movements to accurately track the square u

    E-print Network

    Pylyshyn, Zenon

    Figure 2: Sample of single object tracking trial from one subject showing horizontal gaze to investigate whether gaze may play a role in imagined object-tracking. Method: Thirty-five participants tracked-position (green), finger tap selection (blue) and motion path of tracked object (red). This participants uses

  12. Mirazid shows insignificant activity against ovine fascioliasis.

    PubMed

    Botros, S S; El-Lakkany, N M; Badawy, A A; Mahmoud, S S; Ebeid, F A; Fenwick, A

    2009-10-01

    In a recent study, the fasciolicidal activity of Mirazid (a myrrh-derived drug) and its effect on the function and histopathology of host liver were investigated in Egyptian sheep, with triclabendazole (TCBZ) used as the positive control. Sheep were infected with metacercariae (150/animal) and treated 3 months later, either with Mirazid (10 mg/kg/day for six consecutive days) or TCBZ (a single dose of 10 mg/kg), or left untreated, as controls. When the animals were killed 4 weeks after the end of treatment, no Fasciola flukes or eggs could be found in the animals given TCBZ but the number of flukes found in the Mirazid-treated animals was only 6% lower than that recorded in the untreated sheep (a statistically insignificant difference). In terms of their Fasciola egg loads, serum concentrations of hepatic enzymes and hepatic histopathological changes, the Mirazid-treated sheep appeared very similar to the untreated, infected animals. The TCBZ-treated animals, in contrast, showed remarkably little evidence of hepatic pathology. It therefore appears that, in the treatment of ovine fascioliasis, at least some batches of Mirazid have little, if any, value. PMID:19825282

  13. Drug therapy smartens up

    NASA Astrophysics Data System (ADS)

    Martin, Christian

    2015-11-01

    The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

  14. Drug abuse first aid

    MedlinePLUS

    ... rapid breathing . Downers (depressants) do just the opposite. Mind-altering drugs are called hallucinogens. They include LSD , ... in the recovery position. If the patient is conscious, loosen the clothing, keep the person warm, and ...

  15. Drug allergies

    MedlinePLUS

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... Adverse reactions to drugs are common. (adverse means unwanted or unexpected.) Almost any drug can cause an adverse reaction. Reactions range from irritating ...

  16. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  17. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  18. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  19. Obesity in show cats.

    PubMed

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. PMID:24612018

  20. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  1. Mars Slide Show

    NASA Technical Reports Server (NTRS)

    2006-01-01

    15 September 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a landslide that occurred off of a steep slope in Tithonium Chasma, part of the vast Valles Marineris trough system.

    Location near: 4.8oS, 84.6oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Autumn

  2. Keeping Show Pigs Healthy 

    E-print Network

    Lawhorn, D. Bruce

    2006-10-13

    ? are approved antibiotics commonly used in rations. For more information on feed med- ication for specific diseases, check these Extension publications: Diarrheal Disease in Show Swine, L-5320; and Swine Pneumonia, L-5203. taking care dUring and after... requiring anesthesia, such as removal of a retained testicle (cryptorchidism), removal of an infected and enlarged urine pocket (preputial diverticulum removal), repair of scrotal or umbil- ical hernia, and removal of tumors. Before a sur- geon...

  3. Let the show begin

    SciTech Connect

    Alperowicz, N.

    1993-01-27

    Major changes should occur in the European polyolefins industry this year. BASF's (Ludwigshafen) polypropylene (PP) deal with ICI is expected to be followed by that of Hoechst (Frankfurt) and Petrofina (Brussels). The two are engaged in feasibility studies for a possible joint venture in PP and are expected to make a decision in the second quarter of this year. Shell and Himont are on track to complete their feasibility study in the first quarter for a polyolefins joint venture. And Huels and PCD are still in talks. But two new possible deals, a polyolefins merger between Nests (Helsinki) and Statoil (Stavanger) and an alliance in PP involving Appryl, the Elf Atochem (51%)/BP Chemicals (49%) joint venture, and Solvay have been denied. The Hoechst/Fina venture would initially encompass only the two companies European plants - Hoechst's 550,000-m.t./year and Fina's 180,000 m.t./year. In addition, Fina would either build or acquire another PP plant. In the second stage, the partners could bring in their overseas plants. Fina has plants in the US, and Hoechst has a combined 100,000 m.t./year in south Africa and Australia. Neste's board member Jukka Viinanen says the only talks between Nests and Statoil center on renegotiations of ethylene supply contract at Stenungsund, Sweden. Nests wants a more flexible deal on quantity and price. It needs 400,000 m.t./year of ethylene for its downstream plants. Viinanen adds that he is worried about the European petrochemical industry and producers need to do everything to improve margins through pricing policies and obtaining a balance between supply and demand. On the possibility of a future link with Statoil he comments, One can never say never. It would take time. We don't feel in a very vulnerable position right now.

  4. New Drug Shows Mixed Results Against Early Alzheimer's

    MedlinePLUS

    ... in Women with Alzheimer’s A Few Cups of Coffee a Day May Lower Alzheimer’s Risk Chocolate May ... May Be Less Likely to Get Alzheimer’s Drinking Coffee in Mid-Life May Help Ward Off Alzheimer’s ...

  5. Barriers and Facilitators of Adherence to Antiretroviral Drug Therapy and Retention in Care among Adult HIV-Positive Patients: A Qualitative Study from Ethiopia

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.; Bimirew, Mekides A.; Kassie, Desalew M.

    2014-01-01

    Background Antiretroviral therapy (ART) has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country’s ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. Methods Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. Results Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. Conclusions Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved patient outcomes. PMID:24828585

  6. Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle

    PubMed Central

    Hossain, Kazi Jahangir; Kamal, Md Mustafa; Ahsan, Monira; Islam, SK Nazrul

    2007-01-01

    Background Use of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18–45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry. Results Results showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels. Conclusion Illicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations. PMID:17417973

  7. One size does not fit all: Challenging some dogmas and taboos in drug discovery.

    PubMed

    Chai, Christina Ll; Mátyus, Péter

    2016-01-01

    Advances in genetics, biology, chemical synthesis and computational methods have contributed to the understanding of diseases and drugs and with all of the above, there is an expectation that we are in a better position than ever before to create effective medicines for our needs. The reality is, however, disconnected from the expectation - US FDA drug approval statistics show that the number of approved drugs, especially the first-in-class drugs, is not commensurate with our improved knowledge. In this perspective, we offer our views on the possible reasons for this, focusing on small-molecule drugs and suggest some ideas for further considerations. PMID:26689236

  8. Effects of Drugs and Alcohol on Behavior, Job Performance, and Workplace Safety

    ERIC Educational Resources Information Center

    Elliott, Karen; Shelley, Kyna

    2006-01-01

    A study of records for 1 large U.S. company revealed that employees with positive drug screens were fired, whereas workers who self-disclosed drug/alcohol problems remained employed. Both groups were offered substance abuse intervention, and some previously fired workers were rehired after they received treatment. Accident results showed that…

  9. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre. PMID:25273491

  10. Btu accounting: Showing results

    SciTech Connect

    Nelson, K.E.

    1994-10-01

    In the preceding article in this series last month, the author showed how to calculate the energy consumed to make a pound of product. To realize a payoff, however, the results must be presented in graphs or tables that clearly display what has happened. They must call attention to plant performance and ultimately lead to more efficient use of energy. Energy-consumption reporting is particularly valuable when viewed over a period of time. The author recommend compiling data annually and maintaining a ten-year performance history. Four cases are considered: individual plant performance; site performance for sites having more than one plant; company performance, for companies having more than one site; and performance based on product, for identical or similar products made at different plants or sites. Of these, individual plant performance is inherently the most useful. It also serves as the best basis for site, company and product performance reports. A key element in energy accounting is the relating of all energy consumption to a common basis. As developed last month in Part 1 in this series, the author chose Btu[sub meth] (i.e., Btu of methane equivalent, expressed as its higher heating value) for this purpose. It represents the amount of methane that would be needed to replace (in the case of fuels) or generate (in the case of steam and power) the energy being used.

  11. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    The ESO Very Large Telescope Interferometer, which allows astronomers to scrutinise objects with a precision equivalent to that of a 130-m telescope, is proving itself an unequalled success every day. One of the latest instruments installed, AMBER, has led to a flurry of scientific results, an anthology of which is being published this week as special features in the research journal Astronomy & Astrophysics. ESO PR Photo 06a/07 ESO PR Photo 06a/07 The AMBER Instrument "With its unique capabilities, the VLT Interferometer (VLTI) has created itself a niche in which it provide answers to many astronomical questions, from the shape of stars, to discs around stars, to the surroundings of the supermassive black holes in active galaxies," says Jorge Melnick (ESO), the VLT Project Scientist. The VLTI has led to 55 scientific papers already and is in fact producing more than half of the interferometric results worldwide. "With the capability of AMBER to combine up to three of the 8.2-m VLT Unit Telescopes, we can really achieve what nobody else can do," added Fabien Malbet, from the LAOG (France) and the AMBER Project Scientist. Eleven articles will appear this week in Astronomy & Astrophysics' special AMBER section. Three of them describe the unique instrument, while the other eight reveal completely new results about the early and late stages in the life of stars. ESO PR Photo 06b/07 ESO PR Photo 06b/07 The Inner Winds of Eta Carinae The first results presented in this issue cover various fields of stellar and circumstellar physics. Two papers deal with very young solar-like stars, offering new information about the geometry of the surrounding discs and associated outflowing winds. Other articles are devoted to the study of hot active stars of particular interest: Alpha Arae, Kappa Canis Majoris, and CPD -57o2874. They provide new, precise information about their rotating gas envelopes. An important new result concerns the enigmatic object Eta Carinae. Using AMBER with its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave coming from the nova. The stream of results from the VLTI and AMBER

  12. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  13. Prevalence of illicit drug use in patients without controlled substance abuse in interventional pain management.

    PubMed

    Manchikanti, Laxmaiah; Pampati, Vidyasagar; Damron, Kim S; Beyer, Carla D; Barnhill, Renee C

    2003-04-01

    Drug abuse with illicit drugs and licit drugs has been increasing steadily over the past decade. A recent National Household Survey on Drug Abuse found statistically significant increases between 2000 and 2001 in the use of multiple drugs, including marijuana, cocaine, and non-medical use of pain relievers and tranquilizers. Prescription controlled substance abuse is a major issue in chronic pain management. Various means suggested to avoid or monitor abuse in patients in treatment include urine/serum drug screening whenever requested, along with other precautions including one prescribing physician and one designated pharmacy, etc. Based on the present evidence, physicians assume that patients adhering to controlled substance agreements and without obvious dependency behavior do not abuse either illicit or licit drugs. Thus, it is accepted that there is no necessity to perform routine urine/drug testing in this specific group of the patient population. One hundred patients undergoing interventional pain management and receiving controlled substances were randomly selected for evaluation of illicit drug abuse by urine drug testing. They were selected from a total of 250 patients who were identified as non-abusers of prescription drugs. Results showed that illicit drug abuse in patients without history of controlled substance abuse was seen in 16 patients. Thirteen of the 16 patients tested positive for marijuana and 3 patients tested positive for cocaine. Only one patient tested positive for a combined use of both marijuana and cocaine. This study showed that, in an interventional pain management setting, there is significant use of illicit drugs (16%) with 13% use of marijuana and 3% use of cocaine in patients who are considered as non-abusers of prescription controlled substances and those who are adherent to controlled substance agreements. However, if cocaine is considered as a hardcore drug in contrast to marijuana, abuse of hardcore illicit drugs is only 3%. PMID:16883377

  14. Improving Detection of Arrhythmia Drug-Drug Interactions in Pharmacovigilance Data through the Implementation of Similarity-Based Modeling.

    PubMed

    Vilar, Santiago; Lorberbaum, Tal; Hripcsak, George; Tatonetti, Nicholas P

    2015-01-01

    Identification of Drug-Drug Interactions (DDIs) is a significant challenge during drug development and clinical practice. DDIs are responsible for many adverse drug effects (ADEs), decreasing patient quality of life and causing higher care expenses. DDIs are not systematically evaluated in pre-clinical or clinical trials and so the FDA U. S. Food and Drug Administration relies on post-marketing surveillance to monitor patient safety. However, existing pharmacovigilance algorithms show poor performance for detecting DDIs exhibiting prohibitively high false positive rates. Alternatively, methods based on chemical structure and pharmacological similarity have shown promise in adverse drug event detection. We hypothesize that the use of chemical biology data in a post hoc analysis of pharmacovigilance results will significantly improve the detection of dangerous interactions. Our model integrates a reference standard of DDIs known to cause arrhythmias with drug similarity data. To compare similarity between drugs we used chemical structure (both 2D and 3D molecular structure), adverse drug side effects, chemogenomic targets, drug indication classes, and known drug-drug interactions. We evaluated the method on external reference standards. Our results showed an enhancement of sensitivity, specificity and precision in different top positions with the use of similarity measures to rank the candidates extracted from pharmacovigilance data. For the top 100 DDI candidates, similarity-based modeling yielded close to twofold precision enhancement compared to the proportional reporting ratio (PRR). Moreover, the method helps in the DDI decision making through the identification of the DDI in the reference standard that generated the candidate. PMID:26068584

  15. Improving Detection of Arrhythmia Drug-Drug Interactions in Pharmacovigilance Data through the Implementation of Similarity-Based Modeling

    PubMed Central

    Vilar, Santiago; Lorberbaum, Tal; Hripcsak, George; Tatonetti, Nicholas P.

    2015-01-01

    Identification of Drug-Drug Interactions (DDIs) is a significant challenge during drug development and clinical practice. DDIs are responsible for many adverse drug effects (ADEs), decreasing patient quality of life and causing higher care expenses. DDIs are not systematically evaluated in pre-clinical or clinical trials and so the FDA U. S. Food and Drug Administration relies on post-marketing surveillance to monitor patient safety. However, existing pharmacovigilance algorithms show poor performance for detecting DDIs exhibiting prohibitively high false positive rates. Alternatively, methods based on chemical structure and pharmacological similarity have shown promise in adverse drug event detection. We hypothesize that the use of chemical biology data in a post hoc analysis of pharmacovigilance results will significantly improve the detection of dangerous interactions. Our model integrates a reference standard of DDIs known to cause arrhythmias with drug similarity data. To compare similarity between drugs we used chemical structure (both 2D and 3D molecular structure), adverse drug side effects, chemogenomic targets, drug indication classes, and known drug-drug interactions. We evaluated the method on external reference standards. Our results showed an enhancement of sensitivity, specificity and precision in different top positions with the use of similarity measures to rank the candidates extracted from pharmacovigilance data. For the top 100 DDI candidates, similarity-based modeling yielded close to twofold precision enhancement compared to the proportional reporting ratio (PRR). Moreover, the method helps in the DDI decision making through the identification of the DDI in the reference standard that generated the candidate. PMID:26068584

  16. Overview of Selected Drug Trends.

    ERIC Educational Resources Information Center

    Adams, Edgar H.; And Others

    This document begins with a brief overview of findings from national surveys conducted by the National Institute on Drug Abuse which show increasing drug use throughout the 1970s and a decreasing trend in drug use during the 1980s. In spite of this decline, drug use in the U.S. is described as still constituting a major public health problem that…

  17. Drug Reactions

    MedlinePLUS

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

  18. Drug Resistance

    MedlinePLUS

    HIV Treatment Drug Resistance (Last updated 4/29/2015; last reviewed 4/29/2015) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  19. Drug Facts

    MedlinePLUS Videos and Cool Tools

    ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  20. Shows 

    E-print Network

    Langley

    2009-01-01

    The present work examines the construction of race on reality television through the use of an exemplar in this genre, MTV's The Real World. By the sheer fact of its popularity and ubiquity, as The Real World is nearly two ...

  1. Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma

    PubMed Central

    Tavanti, E; Sero, V; Vella, S; Fanelli, M; Michelacci, F; Landuzzi, L; Magagnoli, G; Versteeg, R; Picci, P; Hattinger, C M; Serra, M

    2013-01-01

    Background: Aurora kinases are key regulators of cell cycle and represent new promising therapeutic targets in several human tumours. Methods: Biological relevance of Aurora kinase-A and -B was assessed on osteosarcoma clinical samples and by silencing these genes with specific siRNA in three human osteosarcoma cell lines. In vitro efficacy of two Aurora kinases-targeting drugs (VX-680 and ZM447439) was evaluated on a panel of four drug-sensitive and six drug-resistant human osteosarcoma cell lines. Results: Human osteosarcoma cell lines proved to be highly sensitive to both drugs. A decreased drug sensitivity was observed in doxorubicin-resistant cell lines, most probably related to ABCB1/MDR1 overexpression. Both drugs variably induced hyperploidy and apoptosis in the majority of cell lines. VX-680 also reduced in vitro cell motility and soft-agar cloning efficiency. Drug association experiments showed that VX-680 positively interacts with all conventional drugs used in osteosarcoma chemotherapy, overcoming the cross-resistance observed in the single-drug treatments. Conclusion: Aurora kinase-A and -B represent new candidate therapeutic targets for osteosarcoma. In vitro analysis of the Aurora kinases inhibitors VX-680 and ZM447439 indicated in VX-680 a new promising drug of potential clinical usefulness in association with conventional osteosarcoma chemotherapeutic agents. PMID:24129234

  2. Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

    PubMed Central

    Petoumenos, Kathy; Worm, Signe W; Fontas, Eric; Weber, Rainer; De Wit, Stephane; Bruyand, Mathias; Reiss, Peter; El-Sadr, Wafaa; Monforte, Antonella D'Arminio; Friis-Møller, Nina; Lundgren, Jens D; Law, Matthew G

    2012-01-01

    Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2. Conclusions The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham. PMID:23078769

  3. Do international model drug control laws provide for drug availability?

    PubMed

    2009-01-01

    A preliminary review of the United Nations Office on Drugs and Crime (UNODC) model drug control laws was conducted by the Pain & Policy Studies Group (PPSG) to determine whether the models provided governments with language they can use to carry out the obligation to ensure adequate availability of opioid analgesics for the relief of pain and suffering, specified in the Single Convention on Narcotic Drugs, 1961 as amended, and as recommended by the International Narcotics Control Board in 1995. The results showed that current model laws lack the drug availability provisions. Based on initial positive feedback from the International Narcotics Control Board, the UNODC, and the World Health Organization, the PPSG developed preliminary recommendations based on existing provisions in the Single Convention. The PPSG's main recommendation is that updated model laws are needed and that consideration should be given as to how to achieve this objective. The assessment is offered as a starting point for discussion. The World Health Organization (WHO) considers opioid analgesics to be essential for the treatment of pain, but there are great disparities in their availability among countries of the world, leading to needless pain and suffering. Over a period of 15 years of study and efforts to rectify these disparities, the PPSG has found that national narcotics control laws often do not contain provisions that recognize the dual obligation of governments under the international drug control conventions not only to control narcotic drugs but also to make them adequately available for medical and scientific purposes. International drug control organizations develop and publish model narcotics laws and regulations for governments to use. If these models convey the dual obligations of governments, the models would be considered "balanced," and national governments would have model policy language not only for control of licit drugs, but also for their availability. Most governments have already adopted laws to implement the Single Convention; however, it is not known if they followed the Single Convention itself or model laws. The PPSG conducted this preliminary assessment of whether the models published by the United Nations Office on Drugs and Crime are balanced, using as a guide the 1995 recommendations of the International Narcotics Control Board (www.incb.org/pdf/e/ar/1995/suppl1en.pdf) and the 2000 WHO publication Achieving Balance in National Opioids Control Policies: Guidelines for Assessment (www.painpolicy.wisc.edu/publicat/00whoabi/00whoabi.htm). PMID:19492215

  4. Proper Use of Sulfonamides in Market Show Animals 

    E-print Network

    Faries Jr., Floron C.; Fajt, Virginia

    2008-02-14

    When administering a drug to a show animal, the owner is responsible for ensuring that there will be no drug residues in the animal's urine when it is tested at a show. Sulfonamides are of special concern because, even when they are administered...

  5. Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

    PubMed Central

    Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezs?; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

    2015-01-01

    Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates. PMID:25960144

  6. Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

    NASA Astrophysics Data System (ADS)

    Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezs?; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

    2015-05-01

    Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

  7. Positive Psychology

    ERIC Educational Resources Information Center

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive

  8. Drug Abuse

    MedlinePLUS

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  9. Generic Drugs

    MedlinePLUS

    Generic Drugs: The Same Medicine for Less Money What is a generic drug? A generic is a copy of a brand-name drug. A brand- name drug has a patent. When ... benefit to your health, and you will save money. 7KH IHGHUDO )RRG DQG 'UXJ $GPLQLVWUDWLRQ )'$ UHJXODWHV ERWK ...

  10. Drug diversion.

    PubMed

    Wood, Danielle

    2015-10-01

    Prescription drug diversion has significant health, legal and social implications. Deaths from misuse of prescription drugs account for a significant proportion of overdose deaths. The drugs most commonly involved are analgesics, particularly opioids, and psychoactive drugs, particularly benzodiazepines. Diverted drugs are most often sourced from a family member or friend, but are also sourced from overseas pharmacies or laboratories, or bought from drug dealers. Drug diversion can be mitigated by good prescribing practices. Systems for monitoring the prescribing and dispensing of medicines are being instituted across Australia. PMID:26648654

  11. Drug diversion

    PubMed Central

    Wood, Danielle

    2015-01-01

    SUMMARY Prescription drug diversion has significant health, legal and social implications. Deaths from misuse of prescription drugs account for a significant proportion of overdose deaths. The drugs most commonly involved are analgesics, particularly opioids, and psychoactive drugs, particularly benzodiazepines. Diverted drugs are most often sourced from a family member or friend, but are also sourced from overseas pharmacies or laboratories, or bought from drug dealers. Drug diversion can be mitigated by good prescribing practices. Systems for monitoring the prescribing and dispensing of medicines are being instituted across Australia. PMID:26648654

  12. Homelessness and drug misuse in developing countries: A mathematical approach

    NASA Astrophysics Data System (ADS)

    Bhunu, C. P.

    2014-06-01

    Homelessness and drug-misuse are known to exist like siamese twins. We present a model to capture the dynamics in the growth in the number of homeless (street kids and street adults) and drug misusers. The reproduction numbers of the model are determined and analyzed. Results from this study suggests that adult peer pressure plays a more significant role in the growth of drug-misuse and the number of street kids. This result suggests that in resource constrained settings intervention strategies should be tailor made to target adults whose behaviour influence others to misuse drugs and abuse children. Furthermore, numerical simulations show that homelessness and drug-misuse positively enhances, the growth of each other. Thus, to effectively control these two social problems require strategies targeting both of them.

  13. Drug interactions.

    PubMed

    Boobis, Alan; Watelet, Jean-Baptiste; Whomsley, Rhys; Benedetti, Margherita Strolin; Demoly, Pascal; Tipton, Keith

    2009-01-01

    Drugs for allergy are often taken in combination with other drugs, either to treat allergy or other conditions. In common with many pharmaceuticals, most such drugs are subject to metabolism by P450 enzymes and to transmembrane transport. This gives rise to considerable potential for drug-drug interactions, to which must be added consideration of drug-diet interactions. The potential for metabolism-based drug interactions is increasingly being taken into account during drug development, using a variety of in silico and in vitro approaches. Prediction of transporter-based interactions is not as advanced. The clinical importance of a drug interaction will depend upon a number of factors, and it is important to address concerns quantitatively, taking into account the therapeutic index of the compound. PMID:19601724

  14. Patents Associated with High-Cost Drugs in Australia

    PubMed Central

    Christie, Andrew F.; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M.

    2013-01-01

    Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by “evergreening” blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators. PMID:23577165

  15. In silico modeling to predict drug-induced phospholipidosis

    SciTech Connect

    Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G. Sadrieh, Nakissa

    2013-06-01

    Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure–activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80–81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ? 80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. - Highlights: • New in silico models for predicting drug-induced phospholipidosis (DIPL) are described. • The training set data in the models is derived from the FDA's phospholipidosis database. • We find excellent predictivity values of the models based on external validation. • The models can support drug screening and regulatory decision-making on DIPL.

  16. Patents associated with high-cost drugs in Australia.

    PubMed

    Christie, Andrew F; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M

    2013-01-01

    Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators. PMID:23577165

  17. Effects of Drug Abuse

    MedlinePLUS

    ... Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental ... Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental ...

  18. Deuterated Drugs.

    PubMed

    Howland, Robert H

    2015-09-01

    Many drugs are carbon-based, and carbon-hydrogen bonding is particularly relevant for understanding important properties of drug molecules. Deuteration refers to the selective replacement of protium hydrogen isotope atoms in small-molecule drugs with deuterium hydrogen isotope atoms. Deuteration of a drug is most likely to affect pharmacokinetic properties, such as metabolism, rather than its pharmacodynamic effects. For this reason, the metabolism of certain drugs may be favorably influenced when deuterium is substituted for protium, resulting in improved safety, tolerability, or efficacy. Examples of deuterated drugs that have been evaluated in clinical studies include paroxetine, tetrabenazine, and dextromethorphan. PMID:26325169

  19. Drug testing example for conditional probability Suppose that a drug test for an illegal drug is such that it is 98% accurate in the case of a

    E-print Network

    Gross, Louis J.

    Drug testing example for conditional probability Suppose that a drug test for an illegal drug is such that it is 98% accurate in the case of a user of that drug (e.g. it produces a positive result with probability .98 in the case that the tested individual uses the drug) and 90% accurate in the case of a non

  20. Drugged Driving

    MedlinePLUS

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  1. Drugged Driving

    MedlinePLUS

    ... Abused Drugs Charts Emerging Trends Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... and decrease motor coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  2. Prescription Drugs

    MedlinePLUS

    ... Search Home + Drug Facts Anabolic Steroids Bath Salts Cocaine Cough and Cold Medicine (DXM and Codeine Syrup) ... Map Home Drug Facts Anabolic Steroids Bath Salts Cocaine Cough and Cold Medicine (DXM and Codeine Syrup) ...

  3. Drug Safety

    MedlinePLUS

    ... How it's manufactured Results of animal testing and clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying online from only legitimate pharmacies and taking your medicines correctly.

  4. Drug allergy

    PubMed Central

    2011-01-01

    Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR) not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs. PMID:22165859

  5. Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran.

    PubMed

    Kardan Yamchi, Jalil; Haeili, Mehri; Gizaw Feyisa, Seifu; Kazemian, Hossein; Hashemi Shahraki, Abdolrazagh; Zahednamazi, Fatemeh; Imani Fooladi, Abbas Ali; Feizabadi, Mohammad Mehdi

    2015-12-01

    Absence of mutations within the genes encoding drug targets in some phenotypically drug resistant strains of Mycobacterium tuberculosis suggests possible involvement of alternative mechanisms such as over-expression of efflux pumps. We investigated the expression level of Rv1410c, Rv2459, Rv1218c and Rv1273c efflux pumps gene by real-time quantitative reverse transcription PCR (qRT-PCR) in 31 clinical isolates of M. tuberculosis. Susceptibility to first-line drugs was performed using the proportion method. Twenty one isolates were characterized with drug resistance (DR), and among them 12 showed a significantly elevated level of expression (>4 fold) for at least one of the studied genes encoding for efflux pumps. Point mutations in the katG (codons 315 or 335) and rpoB (codons 456 and 441) genes were found in 42.85% and 66.6% of drug resistant isolates, respectively. Only one isolate showed mutation at position -15 of the inhA promoter region. Among the 7 isolates (33.33%) which had no mutation in the studied regions of drug target genes, 5 isolates showed over-expression for efflux pumps. Our results demonstrated that over-expression of efflux pumps can contribute to drug resistance in M. tuberculosis. PMID:26325681

  6. Sex, drugs and moral goals: reproductive strategies and views about recreational drugs

    PubMed Central

    Kurzban, Robert; Dukes, Amber; Weeden, Jason

    2010-01-01

    Humans, unlike most other species, show intense interest in the activities of conspecifics, even when the activities in question pose no obvious fitness threat or opportunity. Here, we investigate one content domain in which people show substantial interest, the use of drugs for non-medical purposes. Drawing from two subject populations—one undergraduate and one Internet-based—we look at the relationships among (i) abstract political commitments; (ii) attitudes about sexuality; and (iii) views surrounding recreational drugs. Whereas some theories suggest that drug views are best understood as the result of abstract political ideology, we suggest that these views can be better understood in the context of reproductive strategy. We show that, as predicted by a strategic construal, drug attitudes are best predicted by sexual items rather than abstract political commitments and, further, that the relationship between factors such as political ideology and drugs, while positive, are reduced to zero or nearly zero when items assessing sexuality are controlled for. We conclude that considering morality from the standpoint of strategic interests is a potentially useful way to understand why humans care about third party behaviour. PMID:20554547

  7. GWAS and drug targets

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may be leveraged by network information to discover known and new drug targets. Results We find that only a very small fraction of drug targets are directly detected in the relevant GWAS studies. We investigate two possible explanations for this observation. First, we find evidence of negative selection acting on drug target genes as a consequence of strong coupling with the disease phenotype, so reducing the incidence of SNPs linked to the disease. Second, we find that GWAS genes are substantially longer on average than drug targets and than all genes, suggesting there is a length related bias in GWAS results. In spite of the low direct relationship between drug targets and GWAS reported genes, we found these two sets of genes are closely coupled in the human protein network. As a consequence, machine-learning methods are able to recover known drug targets based on network context and the set of GWAS reported genes for the same disease. We show the approach is potentially useful for identifying drug repurposing opportunities. Conclusions Although GWA studies do not directly identify most existing drug targets, there are several reasons to expect that new targets will nevertheless be discovered using these data. Initial results on drug repurposing studies using network analysis are encouraging and suggest directions for future development. PMID:25057111

  8. Drug resistance and Giardia.

    PubMed

    Upcroft, J A; Upcroft, P

    1993-05-01

    Giardiasis is a worldwide disease that can cause serious morbidity. Metronidozole is the current recommended drug for treatment, and is mostly still effective. However, Giardia duodenalis, the causative agent, is capable of developing resistance to high levels of metronidozole and other drugs, in vitro, via a number of mechanisms. Resistance, in vivo, has been reported and many cases of treatment failure have been variously attributed to a number of causes, including resistance. Here, Jacqueline and Peter Upcroft ask: is this the beginning of another chapter of drug resistance? or is the situation likely to remain as a 'few refractory cases'? Should we wait to find out or can we act positively to avert the possibility of yet another valuable drug in our limited pharmacopoeia becoming obsolete? PMID:15463750

  9. Fixed drug eruption to tartrazine.

    PubMed

    Orchard, D C; Varigos, G A

    1997-11-01

    An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions. PMID:9431719

  10. Scaring Kids' Shows Off TV.

    ERIC Educational Resources Information Center

    Raspberry, William

    1980-01-01

    Presents the view that activist groups whose attitude is that television advertising is bad for children are scaring off the advertisers and making it difficult for positive children's programs to obtain funding. (SS)

  11. Positive Psychotherapy

    ERIC Educational Resources Information Center

    Seligman, Martin E. P.; Rashid, Tayyab; Parks, Acacia C.

    2006-01-01

    Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported…

  12. Show Them You Really Want the Job

    ERIC Educational Resources Information Center

    Perlmutter, David D.

    2012-01-01

    Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

  13. Projecting future drug expenditures--1998.

    PubMed

    Mehl, B; Santell, J P

    1998-01-15

    Drug cost projections for 1998, factors that directly influence drug costs, and tools for projecting drug expenditures are discussed. The producer price index indicates that prices for drugs and pharmaceuticals increased 2.1% between January and June 1997; the increase for prescription preparations was 2.7%. Medi-Span data show an average increase for all drug products of 1.02% during the first six months of 1997; First Data-Bank reports a 1.7% increase for the same period. IMS America data, which take account of weighting for individual drugs or drug classes, show the prices of all drugs increasing 2.3% between the second quarters of 1996 and 1997. Drug industry analysts project the overall price increase in the next 12 months at 2-4%. Group purchasing organizations predict an average increase over the next 12 months of 0.56% for contracted drugs and 3.6% for noncontracted drugs. Various health care provider indexes suggest that increases in drug costs could be smaller over the next few years. The current trend of takeovers and mergers of pharmaceutical companies and health systems is likely to continue into 1998. As a result of generic competition and the loss of patent protection for many pharmaceutical products, the number of drugs to be introduced onto the market and the number of drugs in development are expected to escalate until the year 2000. These and other major changes in the health care environment, including changes in drug distribution and controversies over the use of formularies, will make future forecasting difficult. Compared with previous years, smaller increases in drug costs have been projected for 1998 and beyond, but changes in the health care environment mean that greater knowledge will be required to forecast future drug expenditures. PMID:9465976

  14. POSIT: Flexible Shape-Guided Docking For Pose Prediction.

    PubMed

    Kelley, Brian P; Brown, Scott P; Warren, Gregory L; Muchmore, Steven W

    2015-08-24

    We present a new approach to structure-based drug design (POSIT) rigorously built on the simple concept that pose prediction is intimately coupled to the quality and availability of experimental structural data. We demonstrate the feasibility of the approach by performing retrospective analyses on three data sets designed to explore the strengths and weaknesses of POSIT relative to existing methods. We then present results documenting 2.5 years of prospective use of POSIT across a variety of structure-based industrial drug-discovery research projects. We find that POSIT is well-suited to guiding research decision making for structure-based design and, in particular, excels at enabling lead-optimization campaigns. We show that the POSIT framework can drive superior pose-prediction performance and generate results that naturally lend themselves to prospective decision making during lead optimization. We believe the results presented here are (1) the largest prospective validation of a pose prediction method reported to date (71 crystal structures); (2) provide an unprecedented look at the scope of impact of a computational tool; and (3) represent a first-of-its-kind analysis. We hope that this work inspires additional studies that look at the real impact and performance of computational research tools on prospective drug design. PMID:26151876

  15. Glutamatergic transmission in drug reward: implications for drug addiction

    PubMed Central

    D'Souza, Manoranjan S.

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse. PMID:26594139

  16. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  17. Nursing Positions

    MedlinePLUS

    ... Kids Deal With Bullies Pregnant? What to Expect Nursing Positions KidsHealth > Parents > Pregnancy & Baby > All About Breastfeeding > ... and actually needs to feed. Getting Comfortable With Breastfeeding Nursing can be one of the most challenging ...

  18. A Randomized Pilot Study of the Engaging Moms Program for Family Drug Court

    PubMed Central

    Dakof, Gayle A.; Cohen, Jeri B.; Henderson, Craig E.; Duarte, Eliette; Boustani, Maya; Blackburn, Audra; Venzer, Ellen; Hawes, Sam

    2010-01-01

    In response to the need for effective drug court interventions, the effectiveness of the Engaging Moms Program (EMP) versus intensive case management services (ICMS) on multiple outcomes for mothers enrolled in family drug court was investigated. In this intent-to-treat study, mothers (N = 62) were randomly assigned to either usual drug court care or the Engaging Moms drug court program. Mothers were assessed at intake, and 3, 6, 12, and 18 months following intake. Results indicated that at 18 months post drug court enrollment, 77% of mothers assigned to EMP versus 55% of mothers assigned to ICMS had positive child welfare dispositions. There were statistically significant time effects for both intervention groups on multiple outcomes including substance use, mental health, parenting practices, and family functioning. EMP showed equal or better improvement than ICMS on all outcomes. The results suggest that EMP in family drug court is a viable and promising intervention approach to reduce maternal addiction and child maltreatment. PMID:20116961

  19. Tunable drug loading and release from polypeptide multilayer nanofilms

    PubMed Central

    Jiang, Bingbing; Li, Bingyun

    2009-01-01

    Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue) were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibioticloaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients. PMID:19421369

  20. Wedge reflection positivity

    E-print Network

    H. Casini

    2010-09-20

    We show there is a positivity property for Wightman functions which is analogous to the reflection positivity for the euclidean ones. The role of euclidean time reflections is played here by the wedge reflections, which change the sign of the time and one of the spatial coordinates.

  1. Correlation between Drug Market Withdrawals and Socioeconomic, Health, and Welfare Indicators Worldwide

    PubMed Central

    Lee, Kye Hwa; Kim, Grace Juyun

    2015-01-01

    The relationship between the number of withdrawn/restricted drugs and socioeconomic, health, and welfare indicators were investigated in a comprehensive review of drug regulation information in the United Nations (UN) countries. A total of of 362 drugs were withdrawn and 248 were restricted during 1950-2010, corresponding to rates of 12.02±13.07 and 5.77±8.69 (mean±SD), respectively, among 94 UN countries. A socioeconomic, health, and welfare analysis was performed for 33 OECD countries for which data were available regarding withdrawn/restricted drugs. The gross domestic product (GDP) per capita, GDP per hour worked, health expenditure per GDP, and elderly population rate were positively correlated with the numbers of withdrawn and restricted drugs (P<0.05), while the out-of-pocket health expenditure payment rate was negatively correlated. The number of restricted drugs was also correlated with the rate of drug-related deaths (P<0.05). The World Bank data cross-validated the findings of 33 OECD countries. The lists of withdrawn/restricted drugs showed markedly poor international agreement between them (Fleiss's kappa=-0.114). Twenty-seven drugs that had been withdrawn internationally by manufacturers are still available in some countries. The wide variation in the numbers of drug withdrawals and restrictions among countries indicates the need to improve drug surveillance systems and regulatory communication networks. PMID:26538999

  2. Correlation between Drug Market Withdrawals and Socioeconomic, Health, and Welfare Indicators Worldwide.

    PubMed

    Lee, Kye Hwa; Kim, Grace Juyun; Kim, Ju Han

    2015-11-01

    The relationship between the number of withdrawn/restricted drugs and socioeconomic, health, and welfare indicators were investigated in a comprehensive review of drug regulation information in the United Nations (UN) countries. A total of of 362 drugs were withdrawn and 248 were restricted during 1950-2010, corresponding to rates of 12.02±13.07 and 5.77±8.69 (mean±SD), respectively, among 94 UN countries. A socioeconomic, health, and welfare analysis was performed for 33 OECD countries for which data were available regarding withdrawn/restricted drugs. The gross domestic product (GDP) per capita, GDP per hour worked, health expenditure per GDP, and elderly population rate were positively correlated with the numbers of withdrawn and restricted drugs (P<0.05), while the out-of-pocket health expenditure payment rate was negatively correlated. The number of restricted drugs was also correlated with the rate of drug-related deaths (P<0.05). The World Bank data cross-validated the findings of 33 OECD countries. The lists of withdrawn/restricted drugs showed markedly poor international agreement between them (Fleiss's kappa=-0.114). Twenty-seven drugs that had been withdrawn internationally by manufacturers are still available in some countries. The wide variation in the numbers of drug withdrawals and restrictions among countries indicates the need to improve drug surveillance systems and regulatory communication networks. PMID:26538999

  3. Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles.

    PubMed

    Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

    2013-11-01

    In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcome drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance. PMID:24055719

  4. Biophysics of Cell Membrane Lipids in Cancer Drug Resistance: Implications for Drug Transport and Drug Delivery with Nanoparticles

    PubMed Central

    Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

    2013-01-01

    In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcoming drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance. PMID:24055719

  5. Nanotopography applications in drug delivery.

    PubMed

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2015-12-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  6. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  7. Ethyl Glucuronide Positivity Rate in a Pain Management Population.

    PubMed

    Johnson-Davis, Kamisha L; Slawson, Matthew H

    2015-11-01

    Ethanol may be consumed by some patients as a means to manage their pain or psychiatric disorder. Consequently, there is the potential to consider ethanol a co-therapeutic in pain management. The purpose of this study was to perform a retrospective analysis to evaluate the rate of ethanol use in a population of patients in pain management programs that were evaluated by our in-house pain management drug panel test. Results from this retrospective study showed that 12.6% of patients in a pain management population were positive for the direct ethanol metabolite, ethyl glucuronide (EtG), by immunoassay. Furthermore, 86% of the individuals positive for EtG were also positive for prescription pain medication and illicit drugs. Results presented here suggest that ethanol use should be routinely monitored in pain management populations in an effort to determine any potential adverse effects of ethanol-drug interactions and as a way to further evaluate the effect of ethanol on pain management outcomes. Testing this population of patients suggests that ethanol use is prevalent and the risk of drug-ethanol adverse effects should be monitored in a pain management population. PMID:26324207

  8. 28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS LINCOLN BOULEVARD, BIG LOST RIVER, AND NAVAL REACTORS FACILITY. F.C. TORKELSON DRAWING NUMBER 842-ARVFS-101-2. DATED OCTOBER 12, 1965. INEL INDEX CODE NUMBER: 075 0101 851 151969. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  9. Micro-Fluidic Device for Drug Delivery

    NASA Technical Reports Server (NTRS)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  10. Drug Testing.

    ERIC Educational Resources Information Center

    Legal Memorandum, 1987

    1987-01-01

    A number of legal issues are involved in conducting a drug testing program to determine whether students--and occasionally teachers--are using illegal drugs. Two legal issues have been raised concerning the accuracy of the urinalysis test: whether it is chemically accurate and whether appropriate procedures have been followed to make certain that…

  11. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  12. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

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

  13. Position indicator

    DOEpatents

    Tanner, David E. (Poway, CA)

    1981-01-01

    A nuclear reactor system is described in which a position indicator is provided for detecting and indicating the position of a movable element inside a pressure vessel. The movable element may be a valve element or similar device which moves about an axis. Light from a light source is transmitted from a source outside the pressure vessel to a first region inside the pressure vessel in alignment with the axis of the movable element. The light is redirected by a reflector prism to a second region displaced radially from the first region. The reflector prism moves in response to movement of the movable element about its axis such that the second region moves arcuately with respect to the first region. Sensors are arrayed in an arc corresponding to the arc of movement of the second region and signals are transmitted from the sensors to the exterior of the reactor vessel to provide indication of the position of the movable element.

  14. Teens and Prescription Drugs: An Analysis of Recent Trends on the Emerging Drug Threat

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, 2007

    2007-01-01

    This report synthesizes a number of national studies that show the intentional abuse of prescription drugs to get high is a growing concern, particularly among teens. The analysis shows that teens are turning away from street drugs and using prescription drugs to get high. New users of prescription drugs have caught up with new users of marijuana.…

  15. Towards better patient care: drugs to avoid.

    PubMed

    2013-04-01

    Common sense dictates that one should choose tried and tested drugs with proven, concrete benefits that outweigh their adverse effects. Many new drugs are approved each year, often despite a lack of solid evidence that they are any better than existing treatments. Worse, some are approved despite being less effective or more harmful than current options. Massive promotion is used to ensure that such drugs achieve a positive image in the eyes of healthcare professionals and patients. Renowned "opinion leaders" intervene in their favour at conferences and in specialist media, and their opinions are further propagated by specialists in the field. Finally, campaigns in the lay media are used to highlight the target illness, encouraging patients to request a prescription. New data sometimes show that older, initially promising drugs are less effective or more harmful than first thought. For all these reasons, many drugs that are now present on the market are more harmful than beneficial and should be avoided. Unfortunately, negative assessment data and warnings are often drowned in the flood of promotion and advertising. Front-line healthcare professionals who are determined to act in their patients' best interests can find themselves swimming against a tide of specialist opinion, marketing authorisation, and reimbursement decisions. By leaving drugs that are more harmful than beneficial on the market and contenting themselves with simple half-measures, healthcare authorities are failing in their duty to protect patients. Prescrire, a journal funded solely by its subscribers, does not seek to do the work of health authorities, and does not have the means to do so. Prescrire's goal is simply to help healthcare professionals provide better care. The following text lists the principal drugs that we consider more harmful than beneficial, based on our reviews published between 2010 and 2012 in our French edition. These drugs should not be used. Patients and healthcare professionals should reassess ongoing treatments and, if necessary, replace these drugs with proven treatments. Without waiting for the authorities to remove them from the market in a timely manner, as the accumulation of data showing that they are more harmful than beneficial would require. PMID:23662325

  16. Discontinued drugs in 2012: cardiovascular drugs.

    PubMed

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products. PMID:23992034

  17. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug release property to achieve increased therapeutic efficacy and reduced side effects. Nanoparticles and nanoliposomes are emerging areas of nanotechnologies that have already begun to make an impact over new modalities for cancer chemotherapy, diagnosis as well as gene delivery. Presently it is possible to reduce the particle size in such a way that the particles can be easily injected or inhaled and many types of human cells are capable to internalize them. A number of fabrications such as PEGylation, specific antibody conjugation, aptamer ligation, specific ligand binding etc. on the nanosize delivery devices makes them in the streamline of research to particularly target the diseased cells thus avoiding the healthy one. Potential of nanosize carriers to cross the blood brain barrier encourages us to build up a new strategy for delivery of therapeutically active agents to the brain. Nanotechnology is showing an emerging effect in chronic diseases such as diabetes, cancer, neurodegenerative diseases etc. Nanosize vaccines are having greater effect in production of better immunity against pathogens through direct administration of medication to the specialized dendritic cells in the immune systems. Lots of hopes and speculations are reigning around the scientists with nanosize drug delivery systems that may revolutionize the drug delivery with the better understanding of drug action mechanism and identification of biomarker associated with specific diseases. Nanosize drug delivery systems are emerging with the promising strategies for efficient targeted drug delivery. The proper designing of these systems can make them capable for being independent in the normal tissue environments and selective at the diseased pharmacological site. Nanomaterials as formulations are already in the market or in clinical trials. Investigation on nanostructural drug delivery is a highly growing field today as an extensive amount of research is on with an expectation to open up new avenues to drug delivery. No doubt the next era of drug therapy will be greater influenced by nanoscale dr

  18. Positively Adolescent!

    ERIC Educational Resources Information Center

    Williamson, Sue

    2000-01-01

    Believes that music teachers should reassess their views toward adolescent behavior in the music classroom by learning to see their behavior in a positive light. Describes teaching strategies that build on four adolescent behaviors: (1) desire for peer acceptance; (2) abundant energy; (3) love of fun; and (4) limited time-managing skills. (CMK)

  19. Bioequivalence of generic drugs.

    PubMed

    Andrade, Chittaranjan

    2015-09-01

    Generic drugs are bioequivalent to the original brand; this is a prerequisite for marketing approval. It is theoretically possible that one generic drug may overestimate the pharmacokinetic (PK) parameters of the original and another generic may underestimate these PK parameters; in consequence, these 2 generics may not be bioequivalent between themselves. The result could be loss of efficacy or development of drug-related adverse effects if these generics are interchanged in stable patients. In a recent study involving 292 indirect comparisons of generic formulations of 9 different drugs, mathematical modeling showed that in most cases (87.0% for maximum concentration, 90.1% for area under the curve, and 80.5% for both) generic drugs are bioequivalent to each other. These reassuring findings notwithstanding, prudence dictates that, in stable patients, generic drugs should be interchanged only if there is a good reason for it. This is because bioequivalent brands of drugs may differ in their excipient content, and this can result in variations in safety profiles. PMID:26455677

  20. Malignant melanoma showing smooth muscle differentiation.

    PubMed Central

    Banerjee, S S; Bishop, P W; Nicholson, C M; Eyden, B P

    1996-01-01

    A unique case of a metastatic non-desmoplastic sarcomatoid malignant melanoma in an axillary lymph node showing smooth muscle differentiation in a 54 year old woman is described. The tumour cells exhibited alpha-smooth muscle actin, HHF-35 and desmin positivity but were negative for S100 protein and HMB-45. Ultrastructural examination revealed smooth muscle phenotype and there was no evidence of myofibroblastic differentiation, a feature described previously in desmoplastic melanomas. Images PMID:8944620

  1. Marijuana and Children. Position Statement

    ERIC Educational Resources Information Center

    Endsley, Patricia; Embrey, Mary Louise

    2014-01-01

    Registered professional school nurses (hereinafter referred to as school nurses) promote wellness and disease prevention to improve health outcomes for our nation's children. It is the position of the National Association of School Nurses (NASN) that the marijuana plant remain under the United States Drug Enforcement Agency's (DEA) Schedule I…

  2. Diarrheal Disease in Show Swine 

    E-print Network

    Lawhorn, D. Bruce

    2007-02-27

    water is the main source of Giardia spp. Bacterial Causes Swine dysentery or ?bloody dysentery? from infec- tion with Brachyspira (Serpulina) hyodysenteriae is a major cause of diarrheal disease in show pigs. Pigs can be exposed to the organism.... Swine dysentery bac- teria are not known to cause disease in humans. Salmonella typhimurium infection is another impor- tant cause of diarrheal disease in show pigs. They become infected by exposure to contaminated swine manure on premises, trailers...

  3. Intradermal Tests for Diagnosis of Drug Allergy are not Affected by a Topical Anesthetic Patch

    PubMed Central

    Silva, Diana; Ferreira, Ana; Cernadas, Josefina R.

    2014-01-01

    The use of topical anesthesia to perform intradermal tests (IDTs) for drug allergy diagnosis was never investigated. We aimed to determine the effects of a topical anesthetic patch containing prilocaine-lidocaine on wheal size of IDT with drugs. Patients who had positive IDT as part of their investigation process of suspected drug hypersensitivity were selected. IDT were performed according to guidelines. Anesthetic patch (AP) was placed and the same prior positive IDT, as well as positive histamine skin prick test (SPT) and negative (saline IDT) controls, were performed in the anesthetized area. Patients with negative IDT were also included to check for false positives with AP. Increase in wheals after 20 minutes both with and without AP was recorded and compared. 45 IDT were performed (36 patients), of which 37 have been previously positive (14 antibiotics, 10 general anesthetics, 6 non-steroidal anti-inflammatory drugs, 3 iodinated contrasts, 3 anti-Hi-histamines and 1 ranitidine). Mean histamine SPT size without the AP was 4.7 mm [95%CI (4.4-5.1]), and 4.6 mm [95%CI(4.2-5.0)] with anesthesia. Mean wheal increase in IDT for drugs without the anesthesia was 4.5 mm [95%CI(3.3-5.7)] and with anesthesia was 4.3 mm [95%CI(2.8-5.8)]. No statistical significant differences were observed between skin tests with or without AP for histamine SPT (P=0.089), IDT with saline (P=0.750), and IDT with drugs (P=0.995). None of the patients with negative IDT showed positivity with the AP, or vice-versa. The use of an AP containing prilocaine-lidocaine does not interfere with IDT to diagnose drug allergy, and no false positive tests were found. PMID:25229004

  4. Drug Interactions

    MedlinePLUS

    ... taking. Also, be sure that your care providers review ALL medications, drugs, and supplements or herbs you are ... of New Mexico Health Sciences Center, and the International Association of Providers of ...

  5. Positive Psychologists on Positive Constructs

    ERIC Educational Resources Information Center

    Lyubomirsky, Sonja

    2012-01-01

    Comments on the original article by McNulty and Fincham (see record 2011-15476-001). In their article, the authors offered compelling evidence that constructs such as forgiveness and optimism can have both beneficial and adverse consequences, depending on the context. Their caution about labeling particular psychological processes as "positive" is…

  6. Drugs@FDA: FDA Approved Drug Products

    MedlinePLUS

    ... Cosmetics Tobacco Products Drugs@FDA: FDA Approved Drug Products FDA Home Drug Databases Drugs@FDA - FAQ | Instructions | ... 6332) Contact FDA For Government For Press Combination Products Advisory Committees Science & Research Regulatory Information Safety Emergency ...

  7. Drug hypersensitivity.

    PubMed

    Bircher, Andreas J

    2014-01-01

    Before the arrival of modern pharmacotherapy, drug hypersensitivity reactions were virtually unknown. Toxicity from the many plant-, animal- and inorganic material-derived remedies must have been much more common. One famous example is the intoxications from mercury, which has been used in many ailments, but particularly for the treatment of syphilis. It was only in the 19th century when more and more active principles from e.g. plants were identified, and when the observations of skin reactions became more prevalent. In 1877, Heinrich Köbner used for the first time the term 'drug exanthema' (Arznei-Exanthem). Since then, many different types of exanthemas from the mild macular-papular forms to the severe life-threatening bullous exanthemas such as toxic epidermal necrolysis have been observed from numerous drugs. The systematic investigation of severe drug reactions has only started in the second half of the 20th century, parallel to the increasing knowledge in immunology. Drug hypersensitivity reactions still remain one of the most challenging problems in allergology due to their manifold clinical manifestations and their very diverse pathophysiology. The introduction of new drugs and in turn the emergence of new hypersensitivity reactions will remain a challenge in the future. PMID:24925392

  8. National Orange Show Photovoltaic Demonstration

    SciTech Connect

    Dan Jimenez Sheri Raborn, CPA; Tom Baker

    2008-03-31

    National Orange Show Photovoltaic Demonstration created a 400KW Photovoltaic self-generation plant at the National Orange Show Events Center (NOS). The NOS owns a 120-acre state fairground where it operates an events center and produces an annual citrus fair known as the Orange Show. The NOS governing board wanted to employ cost-saving programs for annual energy expenses. It is hoped the Photovoltaic program will result in overall savings for the NOS, help reduce the State's energy demands as relating to electrical power consumption, improve quality of life within the affected grid area as well as increase the energy efficiency of buildings at our venue. In addition, the potential to reduce operational expenses would have a tremendous effect on the ability of the NOS to service its community.

  9. Assessment of the consistency among three drug compendia in listing and ranking of drug-drug interactions

    PubMed Central

    Nikoli?, Božana S.; Ili?, Maja S.

    2013-01-01

    Inconsistent information about drug-drug interactions can cause variations in prescribing, and possibly increase the incidence of morbidity and mortality. The aim of this study was to assess whether there is an inconsistency in drug-drug interaction listing and ranking in three authoritative, freely accessible online drug information sources: The British National Formulary; The Compendium about Drugs Licensed for Use in the United Kingdom (the Electronic Medicines Compendium) and the Compendium about Drugs Licensed for Use in the United States (the DailyMed). Information on drug-drug interactions for thirty drugs which have a high or medium potential for interactions have been selected for analysis. In total, 1971 drug-drug interactions were listed in all three drug information sources, of these 992 were ranked as the interactions with the potential of clinical significance. Comparative analysis identified that 63.98% of interactions were listed in only one drug information source, and 66.63% of interactions were ranked in only one drug information source. Only 15.12% listed and 11.19% ranked interactions were identified in all three information sources. Intraclass correlation coefficient indicated a weak correlation among the three drug information sources in listing (0.366), as well as in ranking drug interactions (0.467). This study showed inconsistency of information on drug-drug interaction for the selected drugs in three authoritative, freely accessible online drug information sources. The application of a uniform methodology in assessment of information, and then the presentation of information in a standardized format is required to prevent and adequately manage drug-drug interactions. PMID:24289762

  10. Arches showing UV flaring activity

    NASA Technical Reports Server (NTRS)

    Fontenla, J. M.

    1988-01-01

    The UVSP data obtained in the previous maximum activity cycle show the frequent appearance of flaring events in the UV. In many cases these flaring events are characterized by at least two footpoints which show compact impulsive non-simultaneous brightenings and a fainter but clearly observed arch developes between the footpoints. These arches and footpoints are observed in line corresponding to different temperatures, as Lyman alpha, N V, and C IV, and when observed above the limb display large Doppler shifts at some stages. The size of the arches can be larger than 20 arcsec.

  11. Position Number: 0000XXXX Current Position Information

    E-print Network

    Stuart, Steven J.

    Page 1 Position Number: 0000XXXX Current Position Information Budget Center Name: Department Number: Supervisor's Name: Supervisor's Position Number: Supervisor's State Position Number: Supervisor's State Title: Supervisor's Job Code: Supervisor's Slot: Employee Name: Employee ID: Business Title: State Position Number

  12. Positioning apparatus

    DOEpatents

    Vogel, M.A.; Alter, P.

    1983-07-07

    An apparatus is provided for precisely adjusting the position of an article relative to a beam emerging from a neutron source disposed in a housing. The apparatus includes a support pivotably mounted on a movable base plate and freely suspended therefrom. The support is gravity biased toward the housing and carries an article holder movable in a first direction longitudinally of the axis of said beam and normally urged into engagement against said housing. Means are provided for moving the base plate in two directions to effect movement of the suspended holder in two mutually perpendicular directions, respectively, normal to the axis of the beam.

  13. Positioning apparatus

    DOEpatents

    Vogel, Max A. (Kennewick, WA); Alter, Paul (Richland, WA)

    1986-01-01

    An apparatus for precisely positioning materials test specimens within the optimum neutron flux path emerging from a neutron source located in a housing. The test specimens are retained in a holder mounted on the free end of a support pivotably mounted and suspended from a movable base plate. The support is gravity biased to urge the holder in a direction longitudinally of the flux path against the housing. Means are provided for moving the base plate in two directions to effect movement of the holder in two mutually perpendicular directions normal to the axis of the flux path.

  14. DRUG NAME (INSERT DRUG NAME)

    Cancer.gov

    Supplies-(tools such as oral syringes, disposable spoon, cup, gloves, pad or paper towels, etc. needed to measure or prepare the drug.)List preparation instructionsInsert administration instruction (e.g., with or without food).

  15. 10 CFR 707.8 - Applicant drug testing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy... testing. An applicant for a testing designated position will be tested for the use of illegal drugs before... contractors from conducting drug testing on applicants for employment in any position....

  16. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric positioning chair. (a) Identification. An...

  17. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric positioning chair. (a) Identification. An...

  18. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric positioning chair. (a) Identification. An...

  19. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric positioning chair. (a) Identification. An...

  20. Street Drugs and Pregnancy

    MedlinePLUS

    ... Is it safe? > Street drugs and pregnancy Street drugs and pregnancy Now playing: E-mail to a ... Prescription drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause ...

  1. Postmarket Drug Safety Information

    MedlinePLUS

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Drug Safety and Availability Postmarket Drug ...

  2. 2 Experimental Drugs Offer Hope Against Psoriasis

    MedlinePLUS

    ... 154898.html 2 Experimental Drugs Offer Hope Against Psoriasis: Studies Targeted therapies produce significant results, researchers say ... News) -- Two experimental drugs show promise in treating psoriasis and a related condition, psoriatic arthritis, new studies ...

  3. A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery

    E-print Network

    Konofagou, Elisa E.

    A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery Hong Chen1 the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within

  4. Food and Drug Administration

    MedlinePLUS

    ... isn't enough to keep pets safe. Holiday Food Scraps May Prove Too Tempting Genetically Engineered Salmon Safe to Eat Research shows it's as ... nutritious as any non-GE Atlantic salmon. Genetically Engineered Salmon Safe to Eat National Healthy ... Product Approvals Drugs @ FDA Device Approvals & Clearances Biologics ...

  5. Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

    NASA Astrophysics Data System (ADS)

    Geng, Shengyong; Yang, Bin; Wang, Guowu; Qin, Geng; Wada, Satoshi; Wang, Jin-Ye

    2014-07-01

    In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4?-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4?-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes’ stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats’ retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

  6. Drug testing Example for Conditional Probability and Bayes Theorem Suppose that a drug test for an illegal drug is such that it is 98% accurate in the case of a

    E-print Network

    Gross, Louis J.

    Drug testing Example for Conditional Probability and Bayes Theorem Suppose that a drug test for an illegal drug is such that it is 98% accurate in the case of a user of that drug (e.g. it produces a positive result with probability .98 in the case that the tested individual uses the drug) and 90% accurate

  7. ShowMe3D

    Energy Science and Technology Software Center (ESTSC)

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from themore »displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.« less

  8. Phoenix Scoop Inverted Showing Rasp

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This image taken by the Surface Stereo Imager on Sol 49, or the 49th Martian day of the mission (July 14, 2008), shows the silver colored rasp protruding from NASA's Phoenix Mars Lander's Robotic Arm scoop. The scoop is inverted and the rasp is pointing up.

    Shown with its forks pointing toward the ground is the thermal and electrical conductivity probe, at the lower right. The Robotic Arm Camera is pointed toward the ground.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is led by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  9. [A case of tuberculous meningitis complicated with multiple drug hypersensitivity to antituberculosis agents].

    PubMed

    Arai, Motomi

    2015-01-01

    Multiple drug hypersensitivity (MDH) is an allergy to two or more chemically unrelated drugs. We present a case of MDH caused by antituberculosis agents during the treatment of tuberculous meningitis (TBM). A 64-year-old man without a history of drug allergy developed fever and severe headache. Examination of cerebrospinal fluid showed lymphocytosis, a low glucose level, and a high ADA activity, suggestive of TBM. The patient was treated with isoniazid, rifampicin, pyrazinamide, and ethambutol, and his symptoms resolved quickly. However, 20 days after the initiation of therapy, he developed remittent fever without mucocutaneous lesions. A drug-induced lymphocyte stimulation test was positive for isoniazid, rifampicin, and pyrazinamide, which was consistent with a diagnosis of MDH. All the antituberculosis drugs were replaced with levofloxacin and ethionamide, both of which have excellent cerebrospinal fluid penetration, and the fever subsided. The patient made a full recovery from TBM. Because standard antituberculosis regimens include three or four antituberculosis drugs, it is difficult to determine the culprit drug when hypersensitivity occurs. Moreover, there can be multiple causative drugs as illustrated by the present case. During a time-consuming desensitization therapy, TBM could flare up, leading to permanent neurological damage. Thus, treatment with suitable alternative drugs should be started immediately. PMID:25746078

  10. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  11. Club Drugs

    MedlinePLUS

    ... Bath Salts) Tobacco/Nicotine Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged ... ecstasy or Molly, including how it affects the brain, other health effects, and its potential for addiction. En ... NIDA Notes Articles Narrative of Discovery: In Search of a Medication ...

  12. Can aging be 'drugged'?

    PubMed

    Riera, Celine E; Dillin, Andrew

    2015-12-01

    The engines that drive the complex process of aging are being identified by model-organism research, thereby providing potential targets and rationale for drug studies. Several studies of small molecules have already been completed in animal models with the hope of finding an elixir for aging, with a few compounds showing early promise. What lessons can we learn from drugs currently being tested, and which pitfalls can we avoid in our search for a therapeutic for aging? Finally, we must also ask whether an elixir for aging would be applicable to everyone, or whether we age differently, thus potentially shortening lifespan in some individuals. PMID:26646496

  13. Drug delivery and nanoparticles: Applications and hazards

    PubMed Central

    De Jong, Wim H; Borm, Paul JA

    2008-01-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. PMID:18686775

  14. Casimir experiments showing saturation effects

    SciTech Connect

    Sernelius, Bo E.

    2009-10-15

    We address several different Casimir experiments where theory and experiment disagree. First out is the classical Casimir force measurement between two metal half spaces; here both in the form of the torsion pendulum experiment by Lamoreaux and in the form of the Casimir pressure measurement between a gold sphere and a gold plate as performed by Decca et al.; theory predicts a large negative thermal correction, absent in the high precision experiments. The third experiment is the measurement of the Casimir force between a metal plate and a laser irradiated semiconductor membrane as performed by Chen et al.; the change in force with laser intensity is larger than predicted by theory. The fourth experiment is the measurement of the Casimir force between an atom and a wall in the form of the measurement by Obrecht et al. of the change in oscillation frequency of a {sup 87}Rb Bose-Einstein condensate trapped to a fused silica wall; the change is smaller than predicted by theory. We show that saturation effects can explain the discrepancies between theory and experiment observed in all these cases.

  15. Missionary Positions

    E-print Network

    Cudd, Ann E.

    2005-01-01

    ?to?impose?a?universal?standard?that?merely?serves?the?interests?of?the?imperial?power;?(2)? Amisionism@,?which?atempts?to?change?the?depest?spiritual?comitments?of?the?subjects?of?the? work;?(3)?Eurocentrism?(Americentrism?),?which?atempts?to?impose...?acceptable.?The? final?response?I?make?in?the?paper?is?from?empirical?evidence.?I?argue?that?there?have?ben?succesful? cases?of?humanistic?(non?imperialistic,?non?misionistic,?non?Eurocentric)?intervention?in?opresive? practices.?Al?of?these?responses?show...

  16. 28 CFR 0.157 - Federal Bureau of Investigation-Drug Enforcement Administration Senior Executive Service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...false Federal Bureau of Investigation-Drug Enforcement Administration...157 Federal Bureau of Investigation—Drug Enforcement Administration...within the Federal Bureau of Investigation (FBI) and the Drug Enforcement...competitive service, a career-type permanent position in...

  17. 77 FR 75896 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ...Drug Testing: Determination of Minimum Random Testing Rates for 2013 AGENCY: Federal...Information System, the rail industry's random drug testing positive rate has remained...therefore determined that the minimum annual random drug testing rate for the period...

  18. 78 FR 78275 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ...Drug Testing: Determination of Minimum Random Testing Rates for 2014 AGENCY: Federal...Information System, the rail industry's random drug testing positive rate has remained...therefore determined that the minimum annual random drug testing rate for the period...

  19. Top 100 bestselling drugs represent an arena struggling for new FDA approvals: drug age as an efficiency indicator.

    PubMed

    Polanski, Jaroslaw; Bogocz, Jacek; Tkocz, Aleksandra

    2015-11-01

    We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent years. PMID:26160060

  20. Superhydrophobic coating to delay drug release from drug-loaded electrospun fibrous materials

    NASA Astrophysics Data System (ADS)

    Song, Botao; Xu, Shichen; Shi, Suqing; Jia, Pengxiang; Xu, Qing; Hu, Gaoli; Zhang, Hongxin; Wang, Cuiyu

    2015-12-01

    The drug-loaded electrospun fibrous materials showed attractive applications in biomedical fields; however, the serve burst release of drug from this kind of drug carrier limited its further applications. In this study, inspired by water strong repellency of superhydrophobic surface, the drug-loaded electrospun fibrous mat coated with superhydrophobic layer was constructed to retard and control drug release. The results indicated that the superhydrophobic coating could be simply fabricated on the drug-loaded electrospun mat by the electrospray approach, and the thickness of the superhydrophobic coating could be finely controlled by varying the deposition time. It was further found that, as compared with drug-loaded electrospun mats, drug released sustainably from the samples coated with superhydrophobic layer, and the drug release rate could be controlled by the thickness of superhydrophobic layer. In summary, the current approach of coating a superhydrophobic layer on the drug-loaded electrospun fibrous materials offered a fundament for drug sustained release.

  1. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110...

  2. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110...

  3. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110...

  4. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110...

  5. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110...

  6. Drug models of schizophrenia

    PubMed Central

    Steeds, Hannah; Carhart-Harris, Robin L.

    2015-01-01

    Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia. PMID:25653831

  7. Ultrasonic drug delivery in Oncology.

    PubMed

    Udroiu, Ion

    2015-01-01

    Ultrasound-assisted drug delivery is an emerging technique that has the advantage of being non-invasive, efficiently and specifically targeted and controllable. While systemic drugs often show detrimental side effects, their ultrasound-triggered local release at the selected tissue may improve safety and specifity of therapy. An increasing amount of animal and preclinical studies demonstrates how ultrasound can also be used for increasing the efficacy of chemotherapeutic drug release to solid tumors. In particular, this technique may be functional to reach uniform delivery of chemotherapeutic agents throughout tumors, which is naturally restricted by their abnormal vascularization and interstitial pressure. This review deals with the physical mechanisms of ultrasound, the different kinds of drug carriers (microbubbles, liposomes and micelles) and the biological phenomena useful for cancer treatment (hyperthermia, sonoporation, enhanced extravasation, sonophoresis and blood-brain barrier disruption), showing how much ultrasonic drug delivery is a promising method in the oncological field. PMID:26011326

  8. Orbitrap technology for comprehensive metabolite-based liquid chromatographic-high resolution-tandem mass spectrometric urine drug screening - Exemplified for cardiovascular drugs.

    PubMed

    Helfer, Andreas G; Michely, Julian A; Weber, Armin A; Meyer, Markus R; Maurer, Hans H

    2015-09-01

    LC-high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC-HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC-HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. PMID:26388381

  9. DRUG NAME (INSERT DRUG NAME)

    Cancer.gov

    First, choose a quiet working space away from food, windows, fans or heat ducts. Clean the working space with damp paper towels, and place a pad or paper towel on the clean working space. Next, place all needed items and drug on the pad or paper towel. Then, wash your hands with soap and water, and put on gloves.

  10. 1. Historic American Buildings Survey, August, 1971 STREETSCAPE SHOWING SOUTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey, August, 1971 STREETSCAPE SHOWING SOUTH (FRONT) ELEVATIONS OF LOVE AND BILGER TIN SHOP (FAR LEFT), SACHS BROTHERS STORE, NEUBER'S JEWELRY STORE, KAHLER'S DRUG STORE, BEEKMAN BANK, UNITED STATES HOTEL. - Neuber's Jewelry Store, 130 West California Street, Jacksonville, Jackson County, OR

  11. Drugs of abuse detection in saliva based on actuated optical method

    NASA Astrophysics Data System (ADS)

    Shao, Jie; Li, Zhenyu; Jiang, Hong; Wang, Wenlong; Wu, Yixuan

    2014-12-01

    There has been a considerable increase in the abuse of drugs during the past decade. Combing drug use with driving is very dangerous. More than 11% of drivers in a roadside survey tested positive for drugs, while 18% of drivers killed in accidents tested positive for drugs as reported in USA, 2007. Toward developing a rapid drug screening device, we use saliva as the sample, and combining the traditional immunoassays method with optical magnetic technology. There were several methods for magnetic nanoparticles detection, such as magnetic coils, SQUID, microscopic imaging, and Hall sensors. All of these methods were not suitable for our demands. By developing a novel optical scheme, we demonstrate high-sensitivity detection in saliva. Drugs of abuse are detected at sub-nano gram per milliliter levels in less than 120 seconds. Evanescent wave principle has been applied to sensitively monitor the presence of magnetic nanoparticles on the binding surface. Like the total internal reflection fluorescence microscope (TIRFM), evanescent optical field is generated at the plastic/fluid interface, which decays exponentially and penetrates into the fluid by only a sub-wavelength distance. By disturbance total internal reflection with magnetic nanoparticles, the optical intensity would be influenced. We then detected optical output by imaging the sensor surface onto a CCD camera. We tested four drugs tetrahydrocannabinol (THC), methamphetamine (MAMP), ketamine (KET), morphine (OPI), using this technology. 100 ng mL-1 sensitivity was achieved, and obvious evidence showed that this results could be improved in further researches.

  12. ABT-199 shows effectiveness in CLL.

    PubMed

    2014-09-01

    A phase I trial found that drug ABT-199 controls chronic lymphocytic leukemia in patients whose previous treatments failed. In about a quarter of patients, the drug, which blocks Bcl-2 and triggers cancer cell apoptosis, restored indicators of illness to normal. PMID:25185206

  13. Nucleosome Positioning with Set of Key Positions and Nucleosome Affinity

    PubMed Central

    Wang, Jia; Liu, Shuai; Fu, Weina

    2014-01-01

    The formation and precise positioning of nucleosome in chromatin occupies a very important role of study in life process. Today, many researchers discover that the positioning where the location of a DNA sequence fragment wraps around a histone in genome is not random but regular. However, the positioning is closely relevant to the concrete sequence of core DNA. So in this paper, we analyzed the relation between the affinity and sequence structure of core DNA sequence, and extracted the set of key positions. In these positions, the nucleotide sequences probably occupied mainly action in the binding. First, we simplified and formatted the experimental data by the affinity. Then, to find the key positions in the wrapping, we used neural network to analyze the positive and negative effect of nucleosome generation for every position in core DNA sequences. However, we reached a class of weights with every position to describe this effect. Finally, based on the positions with high weights, we analyzed the reason why the chosen positions are key positions, and used these positions to construct a model of nucleosome positioning predict. Experimental results show the effectiveness of our method. PMID:26322141

  14. Antigiardial drugs.

    PubMed

    Harris, J C; Plummer, S; Lloyd, D

    2001-12-01

    Giardia intestinalis is a world-wide cause of intestinal infection. Treatment of this debilitating disease is usually accomplished using one of several drugs. Metronidazole is the treatment of choice, but benzimidazoles are now being used more frequently. Other treatments include quinacrine, paromomycin and furazolidone. Even though these drugs are all used to treat the same disease, their modes of action differ in all cases. However, resistance is increasing and new alternatives are being sought. New wave antigiardials all appear to have their roots in natural herbal remedies. This mini-review looks at the current treatments available, their efficacy, side effects and different modes of action and addresses a possible way forward using natural products. PMID:11778868

  15. Transmucosal macromolecular drug delivery.

    PubMed

    Prego, C; García, M; Torres, D; Alonso, M J

    2005-01-01

    Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats. PMID:15588901

  16. 75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ...Drug Testing: Determination of Minimum Random Testing Rates for 2011 AGENCY: Federal...determined that the 2009 rail industry random testing positive rates were .037 percent...alcohol. Because the industry-wide random drug testing positive rate has...

  17. Transpapillary Drug Delivery to the Breast

    PubMed Central

    Dave, Kaushalkumar; Averineni, Ranjith; Sahdev, Preety; Perumal, Omathanu

    2014-01-01

    The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple. PMID:25545150

  18. Drug Usage Trends Among College Students

    ERIC Educational Resources Information Center

    Girdano, Daniel A.; Girdano, Dorothy Dusek

    1974-01-01

    The health Education Department of the University of Maryland continuously monitors the drug usage trends on campus. The latest survey (fall, 1973) of 1,385 undergraduates at this school shows that student use of illicit drugs has increased. Alcohol is the most popular drug followed by marijuana, hashish, methaqualone and speed. (Author)

  19. Nanoencapsulation of a crystalline drug.

    PubMed

    Layre, Anne-Magali; Gref, Ruxandra; Richard, Joël; Requier, Denis; Chacun, Hélène; Appel, Martine; Domb, Abraham J; Couvreur, Patrick

    2005-07-25

    The aim of this work was to assess the influence of various formulation parameters on the incorporation of a poorly water-soluble crystalline drug into nanoparticles. For this purpose, the influence of the polymer (polylactic acid, polysebacic acid terminated with lithocholic acid, and polysebacic acid-co-lithocholic acid) as well as the effect of the dispersion medium (aqueous phases at different temperatures, saline medium and ethanol) on the encapsulation was investigated. 3H-labelled drug was used in order to determine the loading efficiency by liquid scintillation counting. The solubility of the drug in the various polymer materials was assessed by differential scanning calorimetry (DSC). The solubility of the drug in the different dispersion media was then determined by gas chromatographic-mass spectrometric measurements. The highest loading ratios were obtained using poly (lactic acid) (PLA). However, the drug solubility in the polymers, determined by DSC analysis, cannot be considered as predictive for encapsulation efficiency. The study of the influence of the liquid outer phase showed that the encapsulation efficiency increased when the drug solubility in the dispersion medium (before acetone evaporation) decreased. These experiments made it possible to propose a mechanism to account for the leakage of the crystalline drug during the nanoprecipitation process. So, when acetone is eliminated by evaporation, the drug solubility in the dispersion medium decreases, leading to the formation of crystals. During nanoparticles storage, the crystals continue to grow, the nanoparticles serving as drug reservoirs. These findings highlight the importance of using a polymer with a specific affinity for the drug, and a dispersion medium with the lowest drug solubility to achieve an efficient encapsulation of a crystalline drug. PMID:15899561

  20. Educational Outreach: The Space Science Road Show

    NASA Astrophysics Data System (ADS)

    Cox, N. L. J.

    2002-01-01

    The poster presented will give an overview of a study towards a "Space Road Show". The topic of this show is space science. The target group is adolescents, aged 12 to 15, at Dutch high schools. The show and its accompanying experiments would be supported with suitable educational material. Science teachers at schools can decide for themselves if they want to use this material in advance, afterwards or not at all. The aims of this outreach effort are: to motivate students for space science and engineering, to help them understand the importance of (space) research, to give them a positive feeling about the possibilities offered by space and in the process give them useful knowledge on space basics. The show revolves around three main themes: applications, science and society. First the students will get some historical background on the importance of space/astronomy to civilization. Secondly they will learn more about novel uses of space. On the one hand they will learn of "Views on Earth" involving technologies like Remote Sensing (or Spying), Communication, Broadcasting, GPS and Telemedicine. On the other hand they will experience "Views on Space" illustrated by past, present and future space research missions, like the space exploration missions (Cassini/Huygens, Mars Express and Rosetta) and the astronomy missions (Soho and XMM). Meanwhile, the students will learn more about the technology of launchers and satellites needed to accomplish these space missions. Throughout the show and especially towards the end attention will be paid to the third theme "Why go to space"? Other reasons for people to get into space will be explored. An important question in this is the commercial (manned) exploration of space. Thus, the questions of benefit of space to society are integrated in the entire show. It raises some fundamental questions about the effects of space travel on our environment, poverty and other moral issues. The show attempts to connect scientific with community thought. The difficulty with a show this elaborate and intricate is communicating on a level understandable for teenagers, whilst not treating them like children. Professional space scientists know how easy it is to lose oneself in technical specifics. This would, of course, only confuse young people. The author would like to discuss the ideas for this show with a knowledgeable audience and hopefully get some (constructive) feedback.

  1. Correlation chart of Pennsylvanian rocks in Alabama, Tennessee, Kentucky, Virginia, West Virginia, Ohio, Maryland, and Pennsylvania showing approximate position of coal beds, coal zones, and key stratigraphic units: Chapter D.2 in Coal and petroleum resources in the Appalachian basin: distribution, geologic framework, and geochemical character

    USGS Publications Warehouse

    Ruppert, Leslie F.; Trippi, Michael H.; Slucher, Ernie R.

    2014-01-01

    In other regions of the basin, group and formation boundaries are more difficult to identify over extensive areas. One example is the placement of the contact between the New River Formation and the overlying Kanawha Formation—a boundary that is not easily defined beyond the area where these units were first defined in West Virginia. At the type section of the Kanawha Formation, the base of the Lower Douglas coal zone (fig. 1) defines the contact between the Kanawha Formation and the underlying New River Formation (Rice and others, 1994b). However, subsequent mapping has demonstrated that the Lower Douglas coal zone is regionally discontinuous and in many parts of West Virginia is absent (Blake and others, 2002). Where absent, the Nuttall Sandstone Member of the underlying New River Formation sometimes occurs in the stratigraphic position of the Lower Douglas coal zone. Yet, even the Nuttall Sandstone Member has been found to be regionally discontinuous and of varying thickness throughout its extent, features that hinder its u

  2. 21 CFR 880.5680 - Pediatric position holder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pediatric position holder. 880.5680 Section 880... Devices § 880.5680 Pediatric position holder. (a) Identification. A pediatric position holder is a device used to hold an infant or a child in a desired position for therapeutic or diagnostic purposes,...

  3. 21 CFR 868.6820 - Patient position support.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Patient position support. 868.6820 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position support is a device intended to maintain the position of an...

  4. 21 CFR 868.6820 - Patient position support.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Patient position support. 868.6820 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position support is a device intended to maintain the position of an...

  5. 21 CFR 868.6820 - Patient position support.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Patient position support. 868.6820 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position support is a device intended to maintain the position of an...

  6. 21 CFR 880.5680 - Pediatric position holder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pediatric position holder. 880.5680 Section 880... Devices § 880.5680 Pediatric position holder. (a) Identification. A pediatric position holder is a device used to hold an infant or a child in a desired position for therapeutic or diagnostic purposes,...

  7. 21 CFR 868.6820 - Patient position support.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Patient position support. 868.6820 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position support is a device intended to maintain the position of an...

  8. 21 CFR 880.5680 - Pediatric position holder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pediatric position holder. 880.5680 Section 880... Devices § 880.5680 Pediatric position holder. (a) Identification. A pediatric position holder is a device used to hold an infant or a child in a desired position for therapeutic or diagnostic purposes,...

  9. 21 CFR 880.5680 - Pediatric position holder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pediatric position holder. 880.5680 Section 880... Devices § 880.5680 Pediatric position holder. (a) Identification. A pediatric position holder is a device used to hold an infant or a child in a desired position for therapeutic or diagnostic purposes,...

  10. 21 CFR 868.6820 - Patient position support.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Patient position support. 868.6820 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position support is a device intended to maintain the position of an...

  11. 21 CFR 880.5680 - Pediatric position holder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pediatric position holder. 880.5680 Section 880... Devices § 880.5680 Pediatric position holder. (a) Identification. A pediatric position holder is a device used to hold an infant or a child in a desired position for therapeutic or diagnostic purposes,...

  12. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  13. Animal Drug Safety FAQs

    MedlinePLUS

    ... determine if a veterinary drug is safe to market? As mandated by the Federal Food, Drug, and ... does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal Drug Applications Process ...

  14. Therapeutic Drug Monitoring

    MedlinePLUS

    ... limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page helpful? ... Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement of ...

  15. Medication/Drug Allergy

    MedlinePLUS

    ... Information > Condition Information > Allergens > Medication/Drug Allergy Medication/Drug Allergy Allergies to medications/drugs are complicated because ... allergy symptoms. Learn more. Doctors Who Treat Medication/Drug Allergy Rohit K. Katial Harold S. Nelson Richard W. ...

  16. Urine drug screen

    MedlinePLUS

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

  17. Drugs Approved for Retinoblastoma

    Cancer.gov

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

  18. Drugs Approved for Neuroblastoma

    Cancer.gov

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

  19. [Drug Exposed Infants and Their Families.

    ERIC Educational Resources Information Center

    Fenichel, Emily, Ed.

    1992-01-01

    This bulletin issue addresses the theme of drug-exposed infants and the services required by these infants and their families. "Cocaine-Exposed Infants: Myths and Misunderstandings" (Barbara J. Myers and others) comments on the negative accounts of drug-exposed babies presented by mass media and reviews the mix of positive and negative findings…

  20. Intelligence and Past Use of Recreational Drugs

    ERIC Educational Resources Information Center

    Wilmoth, Daniel R.

    2012-01-01

    One motivation for trying recreational drugs is the desire for novel experiences. More intelligent people tend to value novelty more highly and may therefore be more likely to have tried recreational drugs. Using data from a national survey, it is shown that intelligence tends to be positively related to the probabilities of having tried alcohol,…

  1. Novel antibiotics targeting respiratory ATP synthesis in Gram-positive pathogenic bacteria.

    PubMed

    Balemans, Wendy; Vranckx, Luc; Lounis, Nacer; Pop, Ovidiu; Guillemont, Jérôme; Vergauwen, Karen; Mol, Selena; Gilissen, Ron; Motte, Magali; Lançois, David; De Bolle, Miguel; Bonroy, Kristien; Lill, Holger; Andries, Koen; Bald, Dirk; Koul, Anil

    2012-08-01

    Emergence of drug-resistant bacteria represents a high, unmet medical need, and discovery of new antibacterials acting on new bacterial targets is strongly needed. ATP synthase has been validated as an antibacterial target in Mycobacterium tuberculosis, where its activity can be specifically blocked by the diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria with little or no effect on the growth of other Gram-positive or Gram-negative bacteria. Here, we identify diarylquinolines with activity against key Gram-positive pathogens, significantly extending the antibacterial spectrum of the diarylquinoline class of drugs. These compounds inhibited growth of Staphylococcus aureus in planktonic state as well as in metabolically resting bacteria grown in a biofilm culture. Furthermore, time-kill experiments showed that the selected hits are rapidly bactericidal. Drug-resistant mutations were mapped to the ATP synthase enzyme, and biochemical analysis as well as drug-target interaction studies reveal ATP synthase as a target for these compounds. Moreover, knockdown of the ATP synthase expression strongly suppressed growth of S. aureus, revealing a crucial role of this target in bacterial growth and metabolism. Our data represent a proof of principle for using the diarylquinoline class of antibacterials in key Gram-positive pathogens. Our results suggest that broadening the antibacterial spectrum for this chemical class is possible without drifting off from the target. Development of the diarylquinolines class may represent a promising strategy for combating Gram-positive pathogens. PMID:22615276

  2. 8. April 1963 MULTIPLE EXPOSURE OF WINDOW DETAIL, SHOWING RECESSED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. April 1963 MULTIPLE EXPOSURE OF WINDOW DETAIL, SHOWING RECESSED VERTICAL SLIDING SHUTTER IN VARIOUS POSITIONS FROM OPEN TO CLOSED - Shaker Ministry's Shop, Shaker Road, Harvard, Worcester County, MA

  3. 37. HANGAR FROM RAILROAD DECK TELESCOPED IN COLUMN & SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    37. HANGAR FROM RAILROAD DECK TELESCOPED IN COLUMN & SHOWING PIN WHICH TRANSFERS LOAD FROM RAILROAD DECK TO TRUSS WHEN IN DOWN POSITION - Armour, Swift, Burlington Bridge, Kansas City, Jackson County, MO

  4. 36. INTERIOR VIEW, BERK SWITCH TOWER, SOUTH NORWALK, SHOWING SWITCHING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. INTERIOR VIEW, BERK SWITCH TOWER, SOUTH NORWALK, SHOWING SWITCHING LEVERS FROM OPERATOR'S POSITION - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT

  5. Characteristics of Indian youth and drug use.

    PubMed

    Beauvais, F

    1992-01-01

    The overall high rates of drug use found among Indian youth may be accounted for in part by lack of educational and employment opportunity and other endemic problems of Indian reservations. Individual drug involvement is most highly related to membership in drug-using peer clusters; but because of physical isolation, links between drug use and close friends are weaker for Indian youth, and family influence is felt more strongly. Anxiety, depression, and low self-esteem are not related to drug involvement, but angry youth are more likely to have drug-involved peers. Risk factors for Indian youth are low family caring, age first drunk, poor school adjustment, weak family sanctions against drugs, positive attitudes toward alcohol use, risk of school dropout, father not at home, and poor religious identification. PMID:1420541

  6. [Emergent drugs (I): smart drugs].

    PubMed

    Burillo-Putze, G; Díaz, B Climent; Pazos, J L Echarte; Mas, P Munné; Miró, O; Puiguriguer, J; Dargan, P

    2011-01-01

    In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects. PMID:21904408

  7. Atomic Level Rendering of DNA-Drug Encounter

    PubMed Central

    Lucas, Maria F.; Cabeza de Vaca, Israel; Takahashi, Ryoji; Rubio-Martínez, Jaime; Guallar, Víctor

    2014-01-01

    Computer simulations have been demonstrated to be important for unraveling atomic mechanisms in biological systems. In this study, we show how combining unbiased molecular dynamic simulations with appropriate analysis tools can successfully describe metal-based drug interactions with DNA. To elucidate the noncovalent affinity of cisplatin’s family to DNA, we performed extensive all-atom molecular dynamics simulations (3.7 ?s total simulation length). The results show that the parent drug, cisplatin, has less affinity to form noncovalent adducts in the major groove than its aquo complexes. Furthermore, the relative position in which the drugs enter the major groove is dependent on the compound’s net charge. Based on the simulations, we estimated noncovalent binding free energies through the use of Markov state models. In addition, and to overcome the lack of experimental information, we employed two additional methods: Molecular Mechanics Poisson-Boltzmann Surface Area (MMPB-SA) and steered molecular dynamics with the Jarzynski estimator, with an overall good agreement between the three methods. All complexes show interaction energies below 3 kcal/mol with DNA but the charged hydrolysis products have slightly more favorable binding free energies than the parent drug. Moreover, this study sets the precedent for future unbiased DNA-ligand simulations of more complex binders. PMID:24461017

  8. Drugs and the Brain.

    ERIC Educational Resources Information Center

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

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

  9. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  10. Interaction network among functional drug groups

    PubMed Central

    2013-01-01

    Background More attention has been being paid to combinatorial effects of drugs to treat complex diseases or to avoid adverse combinations of drug cocktail. Although drug interaction information has been increasingly accumulated, a novel approach like network-based method is needed to analyse that information systematically and intuitively Results Beyond focussing on drug-drug interactions, we examined interactions between functional drug groups. In this work, functional drug groups were defined based on the Anatomical Therapeutic Chemical (ATC) Classification System. We defined criteria whether two functional drug groups are related. Then we constructed the interaction network of drug groups. The resulting network provides intuitive interpretations. We further constructed another network based on interaction sharing ratio of the first network. Subsequent analysis of the networks showed that some features of drugs can be well described by this kind of interaction even for the case of structurally dissimilar drugs. Conclusion Our networks in this work provide intuitive insights into interactions among drug groups rather than those among single drugs. In addition, information on these interactions can be used as a useful source to describe mechanisms and features of drugs. PMID:24555875

  11. Large-Scale Prediction of Beneficial Drug Combinations Using Drug Efficacy and Target Profiles.

    PubMed

    Iwata, Hiroaki; Sawada, Ryusuke; Mizutani, Sayaka; Kotera, Masaaki; Yamanishi, Yoshihiro

    2015-12-28

    The identification of beneficial drug combinations is a challenging issue in pharmaceutical and clinical research toward combinatorial drug therapy. In the present study, we developed a novel computational method for large-scale prediction of beneficial drug combinations using drug efficacy and target profiles. We designed an informative descriptor for each drug-drug pair based on multiple drug profiles representing drug-targeted proteins and Anatomical Therapeutic Chemical Classification System codes. Then, we constructed a predictive model by learning a sparsity-induced classifier based on known drug combinations from the Orange Book and KEGG DRUG databases. Our results show that the proposed method outperforms the previous methods in terms of the accuracy of high-confidence predictions, and the extracted features are biologically meaningful. Finally, we performed a comprehensive prediction of novel drug combinations for 2,639 approved drugs, which predicted 142,988 new potentially beneficial drug-drug pairs. We showed several examples of successfully predicted drug combinations for a variety of diseases. PMID:26624799

  12. Patterns of Drug Use in Fatal Crashes

    PubMed Central

    Romano, Eduardo; Pollini, Robin A.

    2013-01-01

    Aims To characterize drug prevalence among fatally injured drivers, identify significant associations (i.e., day of week, time of day, age, gender), and compare findings with those for alcohol. Design Descriptive and logistic mixed-model regression analyses of Fatality Analysis Reporting System data. Setting U.S. states with drug test results for >80% of fatally injured drivers, 1998-2010. Participants Drivers killed in single-vehicle crashes on public roads who died at the scene of the crash (N=16,942). Measurements Drug test results, blood alcohol concentration (BAC), gender, age, and day and time of crash. Findings Overall, 45.1% of fatally injured drivers tested positive for alcohol (39.9% BAC>0.08) and 25.9% for drugs. The most common drugs present were stimulants (7.2%) and cannabinols (7.1%), followed by “other” drugs (4.1%), multiple drugs (4.1%), narcotics (2.1%), and depressants (1.5%). Drug-involved crashes occurred with relative uniformity throughout the day while alcohol-involved crashes were more common at night (p<.01). The odds of testing positive for drugs varied depending upon drug class, driver characteristics, time of day, and the presence of alcohol. Conclusions Fatal single vehicle crashes involving drugs are less common than those involving alcohol and the characteristics of drug-involved crashes differ depending upon drug class and whether alcohol is present. Concerns about drug-impaired driving should not detract from the current law enforcement focus on alcohol-impaired driving. PMID:23600629

  13. Benign positional vertigo

    MedlinePLUS

    Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal positional vertigo (BPPV). It is caused by a problem in the inner ear. ...

  14. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

  15. Drug distribution in enteric microparticles.

    PubMed

    Nilkumhang, Suchada; Alhnan, Mohamed A; McConnell, Emma L; Basit, Abdul W

    2009-09-01

    The aim of this study was to assess the distribution of three fluorescent drug or drug-like molecules in enteric microparticles. Microparticles were prepared using the pH-responsive methylmethacrylate polymer Eudragit L by an emulsion solvent evaporation process. In the process drug and polymer are dissolved in ethanol, and dispersed in a liquid paraffin external phase using sorbitan sesquioleate as stabiliser. The incorporation and distribution of riboflavin, dipyridamole and acridine orange into these microparticles were investigated using confocal laser scanning microscopy (CLSM). The influence of the physicochemical properties of the molecules (solubility in the inner phase, partition coefficient [ethanol/paraffin]) on the distribution, encapsulation efficiency and pH-responsive dissolution behaviour of the microparticles were examined. The drug that tended to partition in ethanol rather than liquid paraffin (riboflavin) was efficiently encapsulated and evenly distributed. In contrast, compounds which partitioned in favour of the liquid paraffin localised towards the surface of the microparticles and exhibited lower encapsulation efficiency (dipyridamole and acridine orange). All three sets of drug-loaded microparticles showed a limited release in acid (<10% release); drug distribution appeared to have a minimum effect on drug release. This microparticle technology has the potential to provide effective enteric drug release with a wide variety of molecules. PMID:19505543

  16. Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery system.

    PubMed

    Yanagihara, Katsunori

    2002-01-01

    Liposome-encapsulated drugs often exhibit reduced toxicity and have also been shown to enhance retention of drugs in the tissues. Thus, encapsulation of drugs in liposomes has often resulted in an improved overall therapeutic efficacy. The results of efficacy of liposome-encapsulated ciplofloxacin or azithromycin for therapy of intracellular M. avium infection show enhanced cellular delivery of liposome-encapsulated antibiotics and suggest that efficiency of intracellular targeting is sufficient to mediate enhanced antimycobacterial effects. The antitubercular drugs encapsulated in lung specific stealth liposomes have enhanced efficacies against tuberculosis infection in mice. These results from stealth liposome study indicate that antitubercular drugs encapsulated in liposome may provide therapeutic advantages over the existing chemotherapeutic regimen for tuberculosis. Liposomes with encapsulated amikacin are able to protect collagen almost completely from adherence of bacterial cells of all strains examined and prevent from invading of bacteria. PMID:12069384

  17. A Social Norms Approach to Drug Prevention in Schools in Ireland: Results from a Pre Development Study

    ERIC Educational Resources Information Center

    Culleton, Leigheann Ryan; Van Hout, Marie Claire; Foley, Michelle

    2013-01-01

    Research shows that social norms interventions, which aim to educate individuals and groups on their actual attitudinal and behavioural norms relating to alcohol, cigarette and drug use,incur some success in reducing positive attitudes to substance use and rates of substance use. The research aimed to investigate the extent of misperceptions…

  18. Careers in Drug and Alcohol Research: AN Innovative Program for Young Appalachian Women

    NASA Astrophysics Data System (ADS)

    Noland, Melody Powers; Leukefeld, Carl; Reid, Caroline

    Supported by a grant from the National Institute on Drug Abuse, the University of Kentucky's Center on Drug and Alcohol Research developed the Young Women in Science Program to encourage young women from Appalachia to pursue scientific careers ?? drug and alcohol research. This 3-year program, which involved 26 young women entering the ninth grade in 13 counties in southeastern Kentucky, included a summer residential program, community educational sessions, and matching students with mentors. When participants' scores prior to and after the 3-week residential program were compared, it was found that participants increased their science knowledge and improved their scores on confidence in science. Other significant changes occurred as well. These preliminary data indicated that some positive changes resulted from the program, even though contact time with the young women has been modest to date. The program shows considerable promise for providing the encouragement and skills needed for these young women to pursue careers in drug and alcohol research.

  19. Request to Fill a Position Budget position #

    E-print Network

    Arnold, Jonathan

    Request to Fill a Position Department Budget position # Name of requestor Revised January 16, 2015 that the position is mission critical and all funds associated with the request are available and are not required to fill multiple positions (information attached) Once approved (or not), this form should be returned to

  20. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    NASA Astrophysics Data System (ADS)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected

  1. Drug Use among Iranian Drivers Involved in Fatal Car Accidents

    PubMed Central

    Assari, Shervin; Moghani Lankarani, Maryam; Dejman, Masoumeh; Farnia, Marzieh; Alasvand, Ramin; Sehat, Mahmood; Roshanpazooh, Mohsen; Tavakoli, Mahmood; Jafari, Firoozeh; Ahmadi, Khodabakhsh

    2014-01-01

    Background: Although the problem of substance use among drivers is not limited to certain parts of the world, most epidemiological reports on this topic have been published from industrial world. Aim: To investigate pattern of drug use among Iranian drivers who were involved in fatal road accidents. Methods: This study enrolled 51 Iranian adults who were involved in fatal vehicle accidents and were imprisoned thereafter. Data came from a national survey of drug abuse that was done among Iranian prisoners. The survey collected data at the entry to seven prisons in different regions of the country during a 4-month period in 2008. Self-reported lifetime, last year, and last month drug use was measured. Commercial substance screening tests were applied to detect recent substance use (opioids, cannabinoids, methamphetamines, and benzodiazepines). Results: The commercial substance screening test showed three distinct patterns of recent illicit drug use: opioids (37.3%), cannabinoids (2.0%), opioids and cannabinoids (13.7%). 29.4% were also positive for benzodiazepines. The substance use screening test detected 23.5% of participants who had used drugs but did not disclose any substance use. Conclusion: Opioids are the most common illicit drugs being used by Iranian drivers who are involved in fatal car accidents. The high rate of substance use prior to fatal car accidents in Iran advocates for the need for drug use control policies and programs as major strategies for injury prevention in Iran. There is also a need for substance screening among all drivers involved in fatal car accidents in Iran, as more than 20% of users may not disclose substance use. PMID:25221521

  2. Walking on thin ice! Identifying methamphetamine “drug mules” on digital plain radiography

    PubMed Central

    Abdul Rashid, S N; Mohamad Saini, S B; Abdul Hamid, S; Muhammad, S J; Mahmud, R; Thali, M J

    2014-01-01

    Objective: The purpose of this study was to retrospectively evaluate the sensitivity, specificity and accuracy of identifying methamphetamine (MA) internal payloads in “drug mules” by plain abdominal digital radiography (DR). Methods: The study consisted of 35 individuals suspected of internal MA drug containers. A total of 59 supine digital radiographs were collected. An overall calculation regarding the diagnostic accuracy for all “drug mules” and a specific evaluation concerning the radiological appearance of drug packs as well as the rate of clearance and complications in correlation with the reader's experience were performed. The gold standard was the presence of secured drug packs in the faeces. Results: There were 16 true-positivedrug mules” identified. DR of all drug carriers for Group 1 (forensic imaging experienced readers, n?=?2) exhibited a sensitivity of 100%, a mean specificity of 76.3%, positive predictive value (PPV) of 78.5%, negative predictive value (NPV) of 100% and a mean accuracy 87.2%. Group 2 (inexperienced readers, n?=?3) showed a lower sensitivity (93.7%), a mean specificity of 86%, a PPV of 86.5%, an NPV of 94.1% and a mean accuracy of 89.5%. The interrater agreement within Group 1 was 0.72 and within Group 2 averaged to 0.79, indicating a fair to very good agreement. Conclusion: DR is a valuable screening tool in cases of MA body packers with huge internal payloads being associated with a high diagnostic insecurity. Diagnostic insecurity on plain films may be overcome by low-dose CT as a cross-sectional imaging modality and addressed by improved radiological education in reporting drug carriers on imaging. Advances in knowledge: Diagnostic signs (double-condom and halo signs) on digital plain radiography are specific in MA “drug mules”, although DR is associated with high diagnostic insecurity and underreports the total internal payload. PMID:24472728

  3. Frequency and structure of stimulant designer drug consumption among suspected drug users in Budapest and South-East Hungary in 2012-2013.

    PubMed

    Institóris, László; Árok, Zsófia; Seprenyi, Katalin; Varga, Tibor; Sára-Klausz, Gabriella; Keller, Éva; Tóth, Réka A; Sala, Leonardo; Kereszty, Éva; Róna, Kálmán

    2015-03-01

    Identification of abuse and frequency patterns of stimulant designer drugs (SDDs) provides important information for their risk assessment and legislative control. In the present study urine and/or blood samples of suspected drug users in criminal cases were analysed by GC-MS for 38 SDDs, and for the most frequent illicit and psychoactive licit drugs in Hungary. Between July 2012 and June 2013, 2744 suspected drug users were sampled in Budapest and during 2012 and 2013, 774 persons were sampled in South-East Hungary (Csongrád County - neighbour the Romanian and Serbian borders). In Budapest 71.4% of cases, and in South-East Hungary 61% of cases were positive for at least one substance. Pentedrone was the most frequent SDD in both regions; however, the frequency distribution of the remaining drugs was highly diverse. SDDs were frequently present in combination with other drugs - generally with amphetamine or other stimulants, cannabis and/or benzodiazepines. The quarterly distribution of positive samples indicated remarkable seasonal changes in the frequency and pattern of consumption. Substances placed on the list of illicit drugs (mephedrone, 4-fluoro-amphetamine, MDPV, methylone, 4-MEC) showed a subsequent drop in frequency and were replaced by other SDDs (pentedrone, 3-MMC, methiopropamine, etc.). Newly identified compounds from seized materials were added to the list of new psychoactive substances ("Schedule C"). While the risk assessment of substances listed in Schedule C has to be performed within 2 years after scheduling, continuous monitoring of their presence and frequency among drug users is essential. In summary, our results suggest which substances should be dropped from the list of SDDs measured in biological samples; while the appearance of new substances from seized materials indicate the need for developing adequate standard analytical methods. PMID:25671307

  4. 10 CFR 707.8 - Applicant drug testing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug testing. An applicant for a testing designated position will be tested for the use of illegal drugs before final selection for employment or assignment...

  5. 10 CFR 707.8 - Applicant drug testing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug testing. An applicant for a testing designated position will be tested for the use of illegal drugs...

  6. 10 CFR 707.8 - Applicant drug testing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug testing. An applicant for a testing designated position will be tested for the use of illegal drugs...

  7. Applications of a Theory of Drug Use to Prevention Programs.

    ERIC Educational Resources Information Center

    Huba, George J.; And Others

    1980-01-01

    This interactive theory of drug use posits that drug-taking behavior is caused by several constellations of intra- and extra-individual forces. Influences interact to modify each other while determining the presence of a variety of lifestyle behaviors including drug and alcohol use. The model grows as new data are collected. (Author/BEF)

  8. Personality, Drug Preference, Drug Use, and Drug Availability

    ERIC Educational Resources Information Center

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  9. Indices of drug misuse for prescription drugs.

    PubMed

    Davis, H; Baum, C; Graham, D J

    1991-07-01

    Few studies of prescription-drug misuse have taken into account the numbers of prescriptions dispensed for specific drugs. Using data from the Drug Abuse Warning Network (DAWN) and the National Prescription Audit, we calculated indices of drug misuse for specific prescription drugs that are used mainly in outpatient settings and are either benzodiazepines, barbiturates, other sedative-hypnotics, analgesics, or CNS stimulants. In 1983-1985 the drugs associated with the highest numbers of DAWN medical examiner-reported drug-misuse deaths were codeine, diazepam, propoxyphene, phenobarbital, and secobarbital. However, the drugs with the highest indices of DAWN medical examiner-reported drug-misuse deaths/100,000 dispensed prescriptions were methamphetamine, methaqualone, amobarbital, secobarbital, and glutethimide. An index of fatality risk, calculated as 100 x DAWN medical examiner-reported drug-misuse deaths/DAWN emergency room-reported drug-misuse episodes, suggested that the risk of death from a glutethimide-associated drug-misuse episode had increased 92% from 1975-1979 to 1983-1983 and in 1983-1985 was the highest for the drugs studied. These indices might assist public health authorities attempting to design effective strategies to efficiently address the problem of prescription-drug misuse. PMID:1960000

  10. Test implementation of a school-oriented drug prevention program “Study without Drugs”: pre- and post-testing for effectiveness

    PubMed Central

    2014-01-01

    Background In this article, the test implementation of a school-oriented drug prevention program “Study without Drugs” is discussed. The aims of this study were to determine the results of the process evaluation and to determine whether the proposed school-oriented drug prevention program during a pilot project was effective for the participating pupils. Methods Sixty second-grade pupils at a junior high school in Paramaribo, Suriname participated in the test implementation. They were divided into two classes. For the process evaluation the students completed a structured questionnaire focusing on content and teaching method after every lesson. Lessons were qualified with a score from 0–10. The process was also evaluated by the teachers through structured interviews. Attention was paid to reach, dose delivered, dose received, fidelity, connection, achieved effects/observed behaviors, areas for improvement, and lesson strengths. The effect evaluation was conducted by using the General Liniair Model (repeated measure). The research (-design) was a pre-experimental design with pre-and post-test. Results No class or sex differences were detected among the pupils with regard to the assessment of content, methodology, and qualification of the lessons. Post-testing showed that participating pupils obtained an increased knowledge of drugs, their drug-resisting skills were enhanced, and behavior determinants (attitude, subjective norm, self-efficacy, and intention) became more negative towards drugs. Conclusions From the results of the test implementation can be cautiously concluded that the program “Study without Drugs” may yield positive results when applied in schools). Thus, this pilot program can be considered a step towards the development and implementation of an evidence-based school-oriented program for pupils in Suriname. PMID:24920468

  11. Position Measurements Obeying Momentum Conservation

    E-print Network

    Paul Busch; Leon Loveridge

    2011-02-24

    We present a hitherto unknown fundamental limitation to a basic measurement: that of the position of a quantum object when the total momentum of the object and apparatus is conserved. This result extends the famous Wigner-Araki-Yanase (WAY) theorem, and shows that accurate position measurements are only practically feasible if there is a large momentum uncertainty in the apparatus.

  12. 21 CFR 868.5965 - Positive end expiratory pressure breathing attachment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Positive end expiratory pressure breathing attachment. 868.5965 Section 868.5965 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5965 Positive end expiratory pressure...

  13. Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

    PubMed Central

    Sutherland, Jeffrey J.; Daly, Thomas M.; Liu, Xiong; Goldstein, Keith; Johnston, Joseph A.; Ryan, Timothy P.

    2015-01-01

    Pharmaceutical prescribing and drug-drug interaction data underlie recommendations on drug combinations that should be avoided or closely monitored by prescribers. Because the number of patients taking multiple medications is increasing, a comprehensive view of prescribing patterns in patients is important to better assess real world pharmaceutical response and evaluate the potential for multi-drug interactions. We obtained self-reported prescription data from NHANES surveys between 1999 and 2010, and confirm the previously reported finding of increasing drug use in the elderly. We studied co-prescription drug trends by focusing on the 2009-2010 survey, which contains prescription data on 690 drugs used by 10,537 subjects. We found that medication profiles were unique for individuals aged 65 years or more, with ?98 unique drug regimens encountered per 100 subjects taking 3 or more medications. When drugs were viewed by therapeutic class, it was found that the most commonly prescribed drugs were not the most commonly co-prescribed drugs for any of the 16 drug classes investigated. We cross-referenced these medication lists with drug interaction data from Drugs.com to evaluate the potential for drug interactions. The number of drug alerts rose proportionally with the number of co-prescribed medications, rising from 3.3 alerts for individuals prescribed 5 medications to 11.7 alerts for individuals prescribed 10 medications. We found 22% of elderly subjects taking both a substrate and inhibitor of a given cytochrome P450 enzyme, and 4% taking multiple inhibitors of the same enzyme simultaneously. By examining drug pairs prescribed in 0.1% of the population or more, we found low agreement between co-prescription rate and co-discussion in the literature. These data show that prescribing trends in treatment could drive a large extent of individual variability in drug response, and that current pairwise approaches to assessing drug-drug interactions may be inadequate for predicting real world outcomes. PMID:25739022

  14. Detection of Illicit Drugs by Trained Honeybees (Apis mellifera)

    PubMed Central

    Schott, Matthias; Klein, Birgit; Vilcinskas, Andreas

    2015-01-01

    Illegal drugs exacerbate global social challenges such as substance addiction, mental health issues and violent crime. Police and customs officials often rely on specially-trained sniffer dogs, which act as sensitive biological detectors to find concealed illegal drugs. However, the dog “alert” is no longer sufficient evidence to allow a search without a warrant or additional probable cause because cannabis has been legalized in two US states and is decriminalized in many others. Retraining dogs to recognize a narrower spectrum of drugs is difficult and training new dogs is time consuming, yet there are no analytical devices with the portability and sensitivity necessary to detect substance-specific chemical signatures. This means there is currently no substitute for sniffer dogs. Here we describe an insect screening procedure showing that the western honeybee (Apis mellifera) can sense volatiles associated with pure samples of heroin and cocaine. We developed a portable electroantennographic device for the on-site measurement of volatile perception by these insects, and found a positive correlation between honeybee antennal responses and the concentration of specific drugs in test samples. Furthermore, we tested the ability of honeybees to learn the scent of heroin and trained them to show a reliable behavioral response in the presence of a highly-diluted scent of pure heroin. Trained honeybees could therefore be used to complement or replace the role of sniffer dogs as part of an automated drug detection system. Insects are highly sensitive to volatile compounds and provide an untapped resource for the development of biosensors. Automated conditioning as presented in this study could be developed as a platform for the practical detection of illicit drugs using insect-based sensors. PMID:26083377

  15. Effects of drugs on mucus clearance.

    PubMed

    Houtmeyers, E; Gosselink, R; Gayan-Ramirez, G; Decramer, M

    1999-08-01

    Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which is a quaternary ammonium compound, has been suggested to decrease CC significantly. Bromhexine, ambroxol and neutral saline seemed not to alter CC, either positively or negatively. Finally, treatment with either amiloride, recombinant human deoxyribonuclease, bromhexine, ambroxol, N-acetylcysteine, S-carboxymethylcysteine or hypertonic saline has been suggested as a possible cause of clinical improvement in patients, such as the experience of dyspnoea, the case of expectoration or the frequency of infective exacerbations. Other agents did not show a clinical benefit. PMID:10515429

  16. [The development from drug to designer drug.

    PubMed

    Askaa, Bjarke; Horwitz, Henrik; Wøien, Vidar André; Høgberg, Lotte C G; Jürgens, Gesche

    2014-10-13

    Synthetic "designer drugs" with hallucinogenic properties have become increasingly popular among recreational drug users in recent years. Some of the designer drugs are chemically modified drugs previously used in treatment of depression and chronic fatigue. The drugs are available from a large number of internet distributers. There is very little knowledge of the clinical symptoms and how intoxicated people should be treated. We present a review of published literature (including 284 intoxicated patients) and experiences from the Danish poison centre concerning two chemical derivatives of earlier registered drugs. PMID:25316367

  17. Diagnosing Dementia—Positive Signs

    MedlinePLUS

    ... Navigation Bar Home Current Issue Past Issues Diagnosing Dementia—Positive Signs Past Issues / Fall 2007 Table of ... easy, affordable blood test that could accurately diagnose Alzheimer's disease (AD)—even before symptoms began to show? Researchers ...

  18. Other Drugs of Abuse

    MedlinePLUS

    ... Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems ... Abuse ... is sometimes called the "love drug" because it makes people feel very friendly and touchy. It also raises body temperature, heart rate, and blood pressure, and can ...

  19. Drugs Approved for Rhabdomyosarcoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  20. Drug induced rhabdomyolysis

    PubMed Central

    Hohenegger, Martin

    2012-01-01

    Rhabdomyolysis is a clinical condition of potential life threatening destruction of skeletal muscle caused by diverse mechanisms including drugs and toxins. Given the fact that structurally not related compounds cause an identical phenotype pinpoints to common targets or pathways, responsible for executing rhabdomyolysis. A drop in myoplasmic ATP paralleled with sustained elevations in cytosolic Ca2+ concentration represents a common signature of rhabdomyolysis. Interestingly, cardiac tissue is hardly affected or only secondary, as a consequence of imbalance in electrolytes or acid–base equilibrium. This dogma is now impaired by compounds, which show up with combined toxicity in heart and skeletal muscle. In this review, cases of rhabdomyolysis with novel recently approved drugs will be explored for new target mechanisms in the light of previously described pathomechanisms. PMID:22560920

  1. Revisiting "the origins of compulsory drug prescriptions".

    PubMed Central

    Marks, H M

    1995-01-01

    It has been argued that today's prescription drug market originated in the arbitrary acts of the US Food and Drug Administration (FDA), which in 1938 issued regulations creating a class of drugs that could be sold by prescription only. On the basis of the FDA's administrative records, I argue that the 1938 regulations on prescription drug labeling were initiated by industry and then agreed to by the FDA; that contemporaries understood and accepted the reasons for restricting the use of certain drugs; and that the subsequent evolution of these regulations is best understood as an FDA effort to limit industry abuses of the prescription labeling system. This decade-long war of position ended when drug manufacturers persuaded the US Congress to enshrine their version of prescription labeling in law in a highly politicized struggle over government's role in the economy. Images FIGURE 1 PMID:7832245

  2. Drugs: What You Should Know

    MedlinePLUS

    ... Your Best Self Smart Snacking Losing Weight Safely Drugs: What to Know KidsHealth > Teens > Drugs & Alcohol > Drugs > ... are downsides (and dangers) to taking drugs. How Drugs Work Drugs are chemicals or substances that change ...

  3. JOB DESCRIPTION POSITION DATA

    E-print Network

    Stephens, Jacqueline

    JOB DESCRIPTION POSITION DATA Position Number: Title Description: Title Code: Title Level: Employee Type: Approved Working Title: Position Type: College/Unit: Standard Hrs/Wk: Department Name: Percent: Supervisory: (if applicable) Duties ORGANIZATIONAL STRUCTURE Reports to Position

  4. Temperature Data Shows Warming in 2001

    NASA Technical Reports Server (NTRS)

    2002-01-01

    TThe figure above depicts how much air temperatures near the Earth's surface changed relative to the global mean temperature from 1951 to 1980. NASA researchers used maps of urban areas derived from city lights data to account for the 'heat island' effect of cities. The red and orange colors show that temperatures are warmer in most regions of the world when compared to the 1951 to 1980 'normal' temperatures. Warming around the world has been widespread, but it is not present everywhere. The largest warming is in Northern Canada, Alaska and Siberia, as indicated by the deeper red colors. The lower 48 United States have become warmer recently, but only enough to make the temperatures comparable to what they were in the 1930s. The scale on the bottom of these temperature anomaly images represent degrees in Celsius. The negative numbers represent cooling and the positive numbers depict warming. Overall, the air temperature near the Earth's surface has warmed by 1oF (0.6oC) globally, on average, over the last century. For more information and additional images, read Satellites Shed Light on a Warmer World. Image courtesy Goddard Institute for Space Studies (GISS).

  5. A Study of Counseling Students' Attitudes Toward Drug Abuse.

    ERIC Educational Resources Information Center

    Miederhoff, Patrick; And Others

    1981-01-01

    Measured counseling students' attitudes toward drug abuse with the Measurement of Attitudes Toward Drugs Scale. Used a self-report confidential questionnaire. Results showed that these students held more punitive attitudes toward drug abuse than other populations. Attitude variation was related to using drugs for recreation. Discusses implications…

  6. 76 FR 59495 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ...assistance, to promote and protect the stability and positive growth of countries in Africa. The stealth with which both marijuana and synthetic drugs such as MDMA (ecstasy) and methamphetamine are produced in Canada and trafficked to the United...

  7. Experimental and Mathematical Studies on the Drug Release Properties of Aspirin Loaded Chitosan Nanoparticles

    PubMed Central

    Wan, Ajun; Shi, Yifei; Zhang, Yueyue; Chen, Yupeng

    2014-01-01

    The study of drug release dynamic is aiming at understanding the process that drugs release in human body and its dynamic characteristics. It is of great significance since these characteristics are closely related to the dose, dosage form, and effect of the drugs. The Noyes-Whitney function is used to represent how the solid material is dissolved into solution, and it is well used in study of drug dynamic. In this research, aspirin (acetylsalicylic acid (ASA)) has been encapsulated with different grades of chitosan (CS) varying in molecular weight (Mw) for the purpose of controlled release. The encapsulation was accomplished by ionic gelation technology based on assembly of positively charged chitosan and negatively charged sodium tripolyphosphate (TPP). The encapsulation efficiency, loading capacity, and drug release behavior of aspirin loaded chitosan nanoparticles (CS-NPs) were studied. It was found that the concentration of TPP and Aspirin, molecular weights of chitosan have important effect on the drug release patterns from chitosan nanoparticles. The results for simulation studies show that the Noyes-Whitney equation can be successfully used to interpret the drug release characteristics reflected by our experimental data. PMID:24987696

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

    ERIC Educational Resources Information Center

    Harmon, Michele Alicia

    1993-01-01

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

  9. Scheme of the longline used in this study. Numbers show hook position. Ramon Munoz-Chapuli

    E-print Network

    per basket) were 15m long. This stan- dard gear design is modified by ences by each species. Suzuki et Methods The longline gear employed in this study consisted of "baskets" be- tween floats (Fig. 1). Float al. (1977) state that the same fishing methods and longline gear are fre- quently used regardless

  10. Drug-induced hepatitis

    MedlinePLUS

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  11. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  12. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  13. Treating Prescription Drug Addiction

    MedlinePLUS

    ... Abused Drugs Charts Emerging Trends Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... Publication Español PDF (2MB) ePub (820KB) Kindle (1MB) Online Only Featured Publications Drugs, Brains, and Behavior: The ...

  14. Cationic vesicles based on biocompatible diacyl glycerol-arginine surfactants: physicochemical properties, antimicrobial activity, encapsulation efficiency and drug release.

    PubMed

    Tavano, L; Pinazo, A; Abo-Riya, M; Infante, M R; Manresa, M A; Muzzalupo, R; Pérez, L

    2014-08-01

    Physicochemical characteristics of cationic vesicular systems prepared from biocompatible diacyl glycerol-arginine surfactants are investigated. These systems form stable cationic vesicles by themselves and the average diameter of the vesicles decreases as the alkyl chain length of the surfactant increases. The addition of DPPC also modifies the physicochemical properties of these vesicles. Among the drugs these cationic formulations can encapsulate, we have considered Ciprofloxacin and 5-Fluorouracil (5-FU). We show that the percentage of encapsulated drug depends on both the physicochemical properties of the carrier and the type of drug. The capacity of these systems to carry different molecules was evaluated performing in vitro drug release studies. Finally, the antimicrobial activity of empty and Ciprofloxacin-loaded vesicles against Gram-positive and Gram-negative bacteria has been determined. Three bacteria were tested: Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The in vitro drug release from all formulations was effectively delayed. Empty cationic vesicles showed antimicrobial activity and Ciprofloxacin-loaded vesicles showed similar or higher antimicrobial activity than the free drug solution. These results suggest that our formulations represent a great innovation in the pharmaceutical field, due to their dual pharmacological function: one related to the nature of the vehiculated drug and the other related to the innate antibacterial properties of the surfactant-based carriers. PMID:24907585

  15. Pharmacokinetics of Drug Entry into Cochlear Fluids

    PubMed Central

    Salt, Alec N.

    2007-01-01

    The inner ear is exposed to aminoglycosides or other drugs either intentionally or as a side effect of clinical treatments directed at other regions of the body. An understanding of the effects of drugs on the inner ear requires knowledge of the pharmacokinetics of the drug once it reaches the cochlear fluids, specifically how much of it reaches different parts of the ear and how long it stays there before disappearing. Accumulating data show that drug distribution in the inner ear is complex, especially for drugs applied locally to the ear's round window membrane. Locally applied drugs do not disperse rapidly, but instead spread very slowly through the fluid spaces by diffusion so that substantial differences in drug concentration occur in different regions of the ear. In some cases, the drug may leak from the inner ear to the blood as fast as it diffuses, meaning it may never become uniformly distributed even when applied for a long period. In recent years, experimental pharmacokinetic studies have become increasingly quantitative, permitting the results to be interpreted with computer models. Simulations of the drug distribution in animals have been used as a basis to predict the likely drug distribution in the larger, human inner ear. Such studies allow clinical drug delivery protocols to be optimized to minimize inadvertent hearing loss and to deliver therapeutic levels of the drug more effectively. PMID:17330152

  16. 21 CFR 872.1850 - Lead-lined position indicator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to...

  17. 21 CFR 872.1850 - Lead-lined position indicator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to...

  18. 21 CFR 872.1850 - Lead-lined position indicator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to...

  19. 21 CFR 872.1850 - Lead-lined position indicator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to...

  20. 21 CFR 872.1850 - Lead-lined position indicator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to...

  1. 21 CFR 892.5780 - Light beam patient position indicator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Light beam patient position indicator. 892.5780... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5780 Light beam patient position indicator. (a) Identification. A light beam patient position indicator is a device that projects a beam...

  2. 21 CFR 892.5780 - Light beam patient position indicator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Light beam patient position indicator. 892.5780... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5780 Light beam patient position indicator. (a) Identification. A light beam patient position indicator is a device that projects a beam...

  3. 21 CFR 892.5780 - Light beam patient position indicator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Light beam patient position indicator. 892.5780... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5780 Light beam patient position indicator. (a) Identification. A light beam patient position indicator is a device that projects a beam...

  4. 21 CFR 892.5780 - Light beam patient position indicator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Light beam patient position indicator. 892.5780... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5780 Light beam patient position indicator. (a) Identification. A light beam patient position indicator is a device that projects a beam...

  5. Missed Opportunities: Drugs and Drugs Education.

    ERIC Educational Resources Information Center

    O'Connor, Louise; Best, David; Best, Rachel; Rowley, Jenny

    1998-01-01

    Explores drug-based knowledge of British primary and secondary school children and the personal experience, attitudes and knowledge of secondary-school children; discusses implications for policymakers and practitioners. Reviews the literature on drug-free lifestyle programs for children, presents a "First Principles" model to underpin drug

  6. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  7. Position Justification Form Position Title PCN #

    E-print Network

    Azad, Abdul-Majeed

    to perform these duties? Please provide or attach an organizational chart, job description, and any data Consultant Position Information New Position Replacement when vacated / / Employee Being Replaced Reason, UnbudgetedYes, BudgetedIs funding budgeted for this position? This questionnaire can be completed in advance

  8. Controllable drug uptake and nongenomic response through estrogen-anchored cyclodextrin drug complex

    PubMed Central

    Yin, Juan-Juan; Shumyak, Stepan P; Burgess, Christopher; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xue-Ji; Pan, Shu-Ting; Yang, Tian-Xin; Duan, Wei; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2015-01-01

    Breast cancer is a leading killer of women worldwide. Cyclodextrin-based estrogen receptor-targeting drug-delivery systems represent a promising direction in cancer therapy but have rarely been investigated. To seek new targeting therapies for membrane estrogen receptor-positive breast cancer, an estrogen-anchored cyclodextrin encapsulating a doxorubicin derivative Ada-DOX (CDE1-Ada-DOX) has been synthesized and evaluated in human breast cancer MCF-7 cells. First, we synthesized estrone-conjugated cyclodextrin (CDE1), which formed the complex CDE1-Ada-DOX via molecular recognition with the derivative adamantane-doxorubicin (Ada-DOX) (Kd =1,617 M?1). The structure of the targeting vector CDE1 was fully characterized using 1H- and 13C-nuclear magnetic resonance, mass spectrometry, and electron microscopy. CDE1-Ada-DOX showed two-phase drug-release kinetics with much slower release than Ada-DOX. The fluorescence polarization analysis reveals that CDE1-Ada-DOX binds to recombinant human estrogen receptor ? fragments with a Kd of 0.027 µM. Competition assay of the drug complex with estrogen ligands demonstrated that estrone and tamoxifen competed with CDE1-Ada-DOX for membrane estrogen receptor binding in MCF-7 cells. Intermolecular self-assembly of CDE1 molecules were observed, showing tail-in-bucket and wire-like structures confirmed by transmission electronic microscopy. CDE1-Ada-DOX had an unexpected lower drug uptake (when the host–guest ratio was >1) than non-targeting drugs in MCF-7 cells due to ensconced ligands in cyclodextrins cavities resulting from the intermolecular self-assembly. The uptake of CDE1-Ada-DOX was significantly increased when the host–guest ratio was adjusted to be less than half at the concentration of CDE1 over 5 µM due to the release of the estrone residues. CDE1 elicited rapid activation of mitogen-activated protein kinases (p44/42 MAPK, Erk1/2) in minutes through phosphorylation of Thr202/Tyr204 in MCF-7 cells. These results demonstrate a targeted therapeutics delivery of CDE1-Ada-DOX to breast cancer cells in a controlled manner and that the drug vector CDE1 can potentially be employed as a molecular tool to differentiate nongenomic from genomic mechanism. PMID:26251594

  9. Effective policy initiatives to constrain lipid-lowering drug expenditure growth in South Korea

    PubMed Central

    2014-01-01

    Background The rapid growth of prescription drug expenditures is a major problem in South Korea. Accordingly, the South Korean government introduced a positive listing system in 2006. They also adopted various price reduction policies. Nevertheless, the total expenditure for lipid-lowering drugs have steadily increased throughout South Korea. The present study explores the factors that have influenced the increased expenditures of lipid-lowering drugs with a particular focus on the effects of statins in this process. Methods This paper investigates the National Health Insurance claims data for prescribed lipid-lowering drugs collected between January 1, 2005 and December 31, 2009. We specifically focused on statins and assessed the yearly variation of statin expenditure by calculating the increased rate of paired pharmaceutical expenditures over a 2 year period. Our study classified statins into three categories: new entrants, core medicines and exiting medicines. For core medicines, we further examined influencing factors such as price, amount of drugs consumed by volume, and prescription changes (substitutes for other drug). Results Statin expenditure showed an average annual increase of 25.7% between 2005 and 2009. Among the different statins, the expenditure of atorvastatin showed a 36.6% annual increase rate, which was the most dramatic among all statins. Also we divided expenditure for core medicines by the price factor, volume factor, and prescription change. The result showed that annual weighted average prices of individual drug decreased each year, which clearly showed that price influenced statin expenditure in a negative direction. The use of generic drugs containing the same active ingredient as name-brand drugs increased and negatively affected statin expenditure (Generic Mix effect). However, the use of relatively expensive ingredients within statin increase, Ingredient Mix effect contributed to increased statin expenditure (Ingredient Mix effect). In particular, the volume effect was found to be critical for increasing statin expenditure as the amount of statin consumed increased steadily throughout the study period. Conclusions The recent rapid increase in statin expenditure can largely be attributed to an increase in consumption volume. In order to check drug expenditures effectively in our current situation, in which chronic diseases remain steadily on the rise, it is necessary to not only have supply-side initiatives such as price reduction, but also demand-side initiatives that could control drug consumption volume, for example: educational programs for rational prescription, generic drug promotional policies, and policies providing prescription targets. PMID:24589172

  10. Drug and alcohol testing in the workplace: moral, ethical and legal issues.

    PubMed

    Raskin, C

    1993-01-01

    The proponents of drug and alcohol testing advance several safety and productivity arguments in support of their position. It is asserted that persons who test positively for drug and alcohol at the workplace experience higher levels of absenteeism and use sick leave to a much greater extent than non-users. Moreover, it is claimed that they have levels of productivity from 10 to 60 per cent lower than persons who do not test positively for drugs or alcohol. Perhaps the greatest argument advanced by those in favour of testing, however, is the safety element. Persons who abuse drugs or who consume alcohol to excess are involved in significantly more accidents than those who test negatively. In other words, proponents take the position that persons who test positively for the presence of drugs or alcohol form a category of individuals and that being in this category is grounds for labelling them as problematic employees. Moreover, so the reasoning goes, the only way to find out if an employee is a member of the category of drug or alcohol users is to test. Opponents of alcohol testing feel that the goal of ensuring a drug- and alcohol-free workplace is reached at too high a social cost and that the testing process constitutes an unwarranted invasion of the privacy of the individual. The provision of urine for analysis is a search, which, if conducted without consent or reason, would constitute an assault. Some opponents to testing feel that the real motivation for testing is controlling employee behaviour. Enterprises impose behavioural constraints on employees that may extend to off-duty times. Moreover, it is advanced that the testing process itself is humiliating to many people. In order to obtain a sample for testing, the person being tested must urinate in the presence of an attendant or supervisor. Often, medical standards are not used. Another moral issue is the implication of discrimination as a result of drug or alcohol testing. Perhaps the greatest concern is the systemic discrimination against disabled persons, persons with acquired immunodeficiency syndrome (AIDS), visible minorities and pregnant women that testing may engender. Again, different countries have addressed the discrimination issue in varying ways. Finally, opponents to drug and alcohol testing question the need to test. It is asserted that all testing shows is that, at some point in time, the person being tested ingested the screened substance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7920542

  11. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  12. A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance

    PubMed Central

    Losasso, Carmen; Cretaio, Erica; Fiorani, Paola; D’Annessa, Ilda; Chillemi, Giovanni; Benedetti, Piero

    2008-01-01

    Human DNA topoisomerase I (hTop1p) catalyzes the relaxation of supercoiled DNA and constitutes the cellular target of the antitumor drug camptothecin (CPT). The X-ray crystal structure of the enzyme covalently joined to DNA and bound to the CPT analog Topotecan suggests that there are two classes of mutations that can produce a CPT-resistant enzyme. The first class includes changes in residues that directly interact with the drug, whereas a second class alters interactions with the DNA and thereby destabilizes the drug binding site. The Thr729Ala, that is part of a hydrophobic pocket in the enzyme C-terminal domain, belongs to a third group of mutations that confer CPT resistance, but do not interact directly with the drug or the DNA. To understand the contribution of this residue in drug resistance, we have studied the effect on hTop1p catalysis and CPT sensitivity of four different substitutions in the Thr729 position (Thr729Ala, Thr729Glu, Thr729Lys and Thr729Pro). Tht729Glu and Thr729Lys mutants show severe CPT resistance and furthermore, Thr729Glu shows a remarkable defect in DNA binding. We postulate that the maintenance of the hydrophobic pocket integrity, where Thr729 is positioned, is crucial for drug sensitivity and DNA binding. PMID:18772225

  13. Drug susceptibility profile of Mycobacterium tuberculosis isolated from HIV infected and uninfected pulmonary tuberculosis patients in eastern India.

    PubMed

    Chakraborty, Nilanjan; De, Chandrav; Bhattacharyya, Sohinee; Mukherjee, Anirban; Santra, Santanu; Banerjee, Dipanjan; Sarkar, Rathindra Nath; Guha, Shubhashish Kamal

    2010-03-01

    HIV is driving the tuberculosis (TB) epidemic in many developing countries including India. This study was initiated to determine the drug resistance pattern of pulmonary TB among 200 HIV seropositive and 50 HIV negative hospitalized patients from different states of Eastern India. The TB positive isolates (120) were screened and characterized by conventional laboratory methods followed by first- and second-line drug susceptibility testing on Lowenstein-Jensen medium by the proportion method. The drug susceptibility testing showed 17.7% (16/90) and 6.6% (2/30) multidrug-resistant (MDR) TB for the HIV positive and HIV negative patients, respectively. 22.2% (4/18) of the isolated MDR-TB cases could be classified as extensively drug-resistant (XDR) TB isolates. 88.8% (16/18) of all the MDR-TB isolates and all XDR-TB isolates were screened from HIV patients. Five (27.7%) of the 18 MDR-TB isolates showed resistance to all the first-line drugs. Mortality rate among the XDR-TB isolates was as high as 75% (3/4). Patients with interrupted anti-TB drug treatment were the ones most affected. These findings are critical and the risk to public health is high, particularly with HIV infected patients. PMID:19828165

  14. The development of multiple drug use among anabolic-androgenic steroid users: six subjective case reports

    PubMed Central

    Skårberg, Kurt; Nyberg, Fred; Engström, Ingemar

    2008-01-01

    Background The inappropriate use of anabolic androgenic steroids (AAS) was originally a problem among athletes but AAS are now often used in nonsport situations and by patients attending regular addiction clinics. The aim of this study was to improve understanding of the development of multiple drug use in patients seeking treatment at an addiction clinic for AAS-related problems. Methods We interviewed six patients (four men and two women) with experience of AAS use who were attending an addiction clinic for what they believed were AAS-related problems. The patients were interviewed in-depth about their life stories, with special emphasis on social background, substance use, the development of total drug use and subjective experienced psychological and physical side effects. Results There was significant variation in the development of drug use in relation to social background, onset of drug use, relationship to AAS use and experience of AAS effects. All patients had initially experienced positive effects from AAS but, over time, the negative experiences had outweighed the positive effects. All patients were dedicated to excess training and took AAS in combination with gym training, indicating that the use of these drugs is closely related to this form of training. Use of multiple drugs was common either in parallel with AAS use or serially. Conclusion The study shows the importance of understanding how AAS use can develop either with or without the concomitant use of other drugs of abuse. The use of AAS can, however, progress to the use of other drugs. The study also indicates the importance of obtaining accurate, comprehensive information about the development of AAS use in designing treatment programmes and prevention strategies in this area. PMID:19040748

  15. Antiarrhythmic drugs and epilepsy.

    PubMed

    Borowicz, Kinga K; Banach, Monika

    2014-08-01

    For a long time it has been suspected that epilepsy and cardiac arrhythmia may have common molecular background. Furthermore, seizures can affect function of the central autonomic control centers leading to short- and long-term alterations of cardiac rhythm. Sudden unexpected death in epilepsy (SUDEP) has most likely a cardiac mechanism. Common elements of pathogenesis create a basis for the assumption that antiarrhythmic drugs (AADs) may affect seizure phenomena and interact with antiepileptic drugs (AEDs). Numerous studies have demonstrated anticonvulsant effects of AADs. Among class I AADs (sodium channel blockers), phenytoin is an established antiepileptic drug. Propafenone exerted low anti-electroshock activity in rats. Lidocaine and mexiletine showed the anticonvulsant activity not only in animal models, but also in patients with partial seizures. Among beta-blockers (class II AADs), propranolol was anticonvulsant in models for generalized tonic-clonic and complex partial seizures, but not for myoclonic convulsions. Metoprolol and pindolol antagonized tonic-clonic seizures in DBA/2 mice. Timolol reversed the epileptiform activity of pentylenetetrazol (PTZ) in the brain. Furthermore, amiodarone, the representative of class III AADs, inhibited PTZ- and caffeine-induced convulsions in mice. In the group of class IV AADs, verapamil protected mice against PTZ-induced seizures and inhibited epileptogenesis in amygdala-kindled rats. Verapamil and diltiazem showed moderate anticonvulsant activity in genetically epilepsy prone rats. Additionally, numerous AADs potentiated the anticonvulsant action of AEDs in both experimental and clinical conditions. It should be mentioned, however, that many AADs showed proconvulsant effects in overdose. Moreover, intravenous esmolol and intra-arterial verapamil induced seizures even at therapeutic dose ranges. PMID:24948053

  16. Positional information, in bits

    PubMed Central

    Dubuis, Julien O.; Tka?ik, Gašper; Wieschaus, Eric F.; Gregor, Thomas; Bialek, William

    2013-01-01

    Cells in a developing embryo have no direct way of “measuring” their physical position. Through a variety of processes, however, the expression levels of multiple genes come to be correlated with position, and these expression levels thus form a code for “positional information.” We show how to measure this information, in bits, using the gap genes in the Drosophila embryo as an example. Individual genes carry nearly two bits of information, twice as much as would be expected if the expression patterns consisted only of on/off domains separated by sharp boundaries. Taken together, four gap genes carry enough information to define a cell’s location with an error bar of along the anterior/posterior axis of the embryo. This precision is nearly enough for each cell to have a unique identity, which is the maximum information the system can use, and is nearly constant along the length of the embryo. We argue that this constancy is a signature of optimality in the transmission of information from primary morphogen inputs to the output of the gap gene network. PMID:24089448

  17. Text Mining for Drug–Drug Interaction

    PubMed Central

    Wu, Heng-Yi; Chiang, Chien-Wei; Li, Lang

    2015-01-01

    In order to understand the mechanisms of drug–drug interaction (DDI), the study of pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PG) data are significant. In recent years, drug PK parameters, drug interaction parameters, and PG data have been unevenly collected in different databases and published extensively in literature. Also the lack of an appropriate PK ontology and a well-annotated PK corpus, which provide the background knowledge and the criteria of determining DDI, respectively, lead to the difficulty of developing DDI text mining tools for PK data collection from the literature and data integration from multiple databases. To conquer the issues, we constructed a comprehensive pharmacokinetics ontology. It includes all aspects of in vitro pharmacokinetics experiments, in vivo pharmacokinetics studies, as well as drug metabolism and transportation enzymes. Using our pharmacokinetics ontology, a PK corpus was constructed to present four classes of pharmacokinetics abstracts: in vivo pharmacokinetics studies, in vivo pharmacogenetic studies, in vivo drug interaction studies, and in vitro drug interaction studies. A novel hierarchical three-level annotation scheme was proposed and implemented to tag key terms, drug interaction sentences, and drug interaction pairs. The utility of the pharmacokinetics ontology was demonstrated by annotating three pharmacokinetics studies; and the utility of the PK corpus was demonstrated by a drug interaction extraction text mining analysis. The pharmacokinetics ontology annotates both in vitro pharmacokinetics experiments and in vivo pharmacokinetics studies. The PK corpus is a highly valuable resource for the text mining of pharmacokinetics parameters and drug interactions. PMID:24788261

  18. Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use

    PubMed Central

    Barson, Jessica R.; Morganstern, Irene; Leibowitz, Sarah F.

    2013-01-01

    Consummatory behavior is driven not just by caloric need but also by emotional need. In the last several decades, a wide variety of models have been used to study the systems that drive food and drug intake. These include selective breeding for a specific trait, manipulation of gene expression, forced or voluntary exposure to a substance, and identification of biomarkers that predict which animals are prone to overconsuming specific substances. From this research, numerous brain areas and neurochemicals have been identified that drive consummatory behavior. While energy homeostasis is primarily mediated by the hypothalamus, reinforcement is more strongly mediated by nuclei outside of the hypothalamus, in mesocorticolimbic regions. Orexigenic neurochemicals that control food intake can provide a general signal for promoting caloric intake or a more specific signal for stimulating consumption of a particular macronutrient, fat, carbohydrate or protein. Those involved in controlling fat ingestion, including galanin, enkephalin, orexin, melanin-concentrating hormone and the endocannabinoids, show positive feedback with this macronutrient, with these peptides both increasing fat intake and being further stimulated by its intake. This positive relationship offers some explanation for why foods high in fat are so often overconsumed. Consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by these neurochemical systems involved in fat intake, consistent with evidence closely relating fat and ethanol consumption. Further understanding of these systems involved in consummatory behavior will allow researchers to develop effective therapies for the treatment of overeating as well as drug abuse. PMID:23520598

  19. Nonnatural deaths among users of illicit drugs: pathological findings and illicit drug abuse stigmata.

    PubMed

    Delaveris, Gerd Jorunn Møller; Hoff-Olsen, Per; Rogde, Sidsel

    2015-03-01

    The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (?-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions. Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative. PMID:25590496

  20. POSITION MANAGEMENT ACTION FORM

    E-print Network

    Su, Xiao

    POSITION MANAGEMENT ACTION FORM HUMAN RESOURCES | 408-924-2250 classcomp@sjsu.edu HR Revised 12/15/2014 Page 1 of 2 Instructions: 1. To be used for all position management actions. Actions may include updating an existing position, establishing a new position, or changing the funding of a position. (For

  1. Additional Notes Position Title

    E-print Network

    Snider, Barry B.

    Additional Notes Position Title New Position Replacement Position Previous Incumbent Hours Request (JOR) For Temporary Staff Positions Only Acct - 4 digits Fund - 2 digits DeptID - 5 digits Program Position Funding Information Signatures/Approvals University, Gift, and/or Endowed Funding (Required

  2. Human egocentric position estimation.

    PubMed

    Yazdanbakhsh, Arash; Gagliardi, Celia

    2015-09-01

    The study of egocentric position estimation may shed light on visuospatial memory processes, such as physical space representation in our visual system. However, little has been done to test egocentric position estimation in humans and the few studies to date have investigated egocentric position estimation with context to ground or other stable visual cues. In this study, human participants are introduced to a three-dimensional virtual reality (VR) generated by a 120 Hz projector with a polarization filter and polarizing glasses that separated left and right eye images in a frame sequential stereoscopic configuration. Participants were placed in the center of a VR cylinder where 5,000 sesame dots were distributed at random distances (112cm to 168cm) from the participant, azimuth (+/- 29.12°), and height (120cm to 188cm from the floor). Nine possible targets were located on a horizontal plane 50cm from the participant's eye level on a three by three matrix at right, left, center azimuths (+/- 18.64°, 0°), and near, middle, and far distances (126cm, 137cm, 147cm from the participant). Participants were presented with one randomly selected target for 3 to 5 seconds before the target was relocated to a random location within the sesame dot field. The task was to reposition the target back to the original position. Depth was induced using disparity and size cues, except for sesame dots that had only disparity cues. Errors in distance repositioning occurred along the line of sight and repositioning showed an attraction bias toward the relocated target. Elevation repositioning was higher for farther targets (P < 0.05, F = 3.19). Azimuth repositioning for left targets were significantly shifted to the right (P< 0.01, F= 18.42). Standard deviations for distance repositioning were invariant against target distance, suggesting that egocentric visuospatial representation is based on Cartesian metrics rather than polar coordinates. Meeting abstract presented at VSS 2015. PMID:26326643

  3. Positive basis for surface skein algebras

    PubMed Central

    Thurston, Dylan Paul

    2014-01-01

    We show that the twisted SL2 skein algebra of a surface has a natural basis (the bracelets basis) that is positive, in the sense that the structure constants for multiplication are positive integers. PMID:24982193

  4. Influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions.

    PubMed

    Shen, Cheng-Ying; Li, Rui-Sheng; Shen, Bao-de; Shen, Gang; Wang, Li-Qiang; Zheng, Juan; Li, Xiao-Rong; Min, Hong-Yan; Han, Jin; Yuan, Hai-Long

    2015-12-01

    The purpose of this paper was to study the influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions. Four drug nanosuspensions were produced by high-pressure homogenization technique, which were the same in stabilizer and similar in particle size. Differential scanning calorimetry and powder X-ray diffraction analysis showed that the crystalline state of the nanocrystals did not change. In vitro permeation study demonstrated that the drug nanosuspensions have a higher rate of permeation that ranged from 1.69- to 3.74-fold compared to drug microsuspensions. Correlation analysis between drug physicochemical properties and Jss revealed that log P and pKa were factors that influenced the in vitro transdermal absorption of hydrophobic drug nanosuspensions, and drugs with a log P value around 3 and a higher pKa value (when pKa?

  5. Antiprotozoal Activity Profiling of Approved Drugs: A Starting Point toward Drug Repositioning

    PubMed Central

    Kaiser, Marcel; Mäser, Pascal; Tadoori, Leela Pavan; Ioset, Jean-Robert; Brun, Reto

    2015-01-01

    Neglected tropical diseases cause significant morbidity and mortality and are a source of poverty in endemic countries. Only a few drugs are available to treat diseases such as leishmaniasis, Chagas’ disease, human African trypanosomiasis and malaria. Since drug development is lengthy and expensive, a drug repurposing strategy offers an attractive fast-track approach to speed up the process. A set of 100 registered drugs with drug repositioning potential for neglected diseases was assembled and tested in vitro against four protozoan parasites associated with the aforementioned diseases. Several drugs and drug classes showed in vitro activity in those screening assays. The results are critically reviewed and discussed in the perspective of a follow-up drug repositioning strategy where R&D has to be addressed with limited resources. PMID:26270335

  6. Optimization of Drug Delivery by Drug-Eluting Stents.

    PubMed

    Bozsak, Franz; Gonzalez-Rodriguez, David; Sternberger, Zachary; Belitz, Paul; Bewley, Thomas; Chomaz, Jean-Marc; Barakat, Abdul I

    2015-01-01

    Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices. PMID:26083626

  7. Optimization of Drug Delivery by Drug-Eluting Stents

    PubMed Central

    Bozsak, Franz; Gonzalez-Rodriguez, David; Sternberger, Zachary; Belitz, Paul; Bewley, Thomas; Chomaz, Jean-Marc; Barakat, Abdul I.

    2015-01-01

    Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices. PMID:26083626

  8. Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs.

    PubMed

    Neuman, Manuela G; Cohen, Lawrence; Nanau, Radu M; Hwang, Paul A

    2012-05-01

    Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR). We aimed (1) to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically; (2) to correlate LTA results with the clinical syndrome; (3) to correlate LTA results with the human leukocyte antigen (HLA) allele B?1502 (HLA-B?1502) positivity in a Han Chinese-Canadian population; and (4) to determine the cytokine network in this population. Patients that developed fever and cutaneous eruptions in the presence or absence of organ involvement within 8 weeks of exposure to carbamazepine (CBZ), phenytoin (PHY), or lamotrigine (LTG) were enrolled. Control patients received AEDs without presenting HSR. We investigated 10 CBZ-HSR patients (4 with Stevens-Johnson syndrome [SJS]), 24 CBZ-controls, 10 PHY-HSR patients (4 with drug-induced liver injury [DILI]), 24 PHY-controls,6 LTG-HSR patients (1 with SJS and 1 with DILI), and 24 LTG-controls. There were 30 Han Chinese individuals (14 HSR patients and 16 controls) in our cohort. LTA toxicity greater than 12.5%±2.5% was considered positive. Differences among groups were determined by analysis of variance. In addition, we measured cytokine secretion in the patient sera between 1 month and 3 years after the event. All Han Chinese individuals and 30% of Caucasians were genotyped for HLA-B?1502. A perfect correlation (r=0.92) was observed between positive LTA and clinical diagnosis of DILI and SJS/toxic epidermal necrolysis (TEN). HLA-B?1502 positivity in Han Chinese is a predictor of CBZ-HSR and PHY-HSR. HLA-B?1502-negative Han Chinese receiving only CBZ or a combination of CBZ and PHY tolerated the drug(s) clinically, presenting negative CBZ-LTA and PHY-LTA. However, 3 patients presenting negative CBZ-LTA and PHY-LTA, as well as negative HLA-B?1502, showed positive LTG-LTA (38%, 28%, and 25%, respectively), implying that they should not be prescribed LTG. Three patients had LTA positive to both PHY and CBZ, and 3 others had LTA positive to both PHY and LTG. Clinically, all 6 patients presented HSR to both drugs that they tested positive to (cross-reactivity). Patients were grouped based on the clinical presentation of their symptoms as only rash and fever or as a triad of rash, fever and DILI or SJS/TEN that characterizes "true" HSR. Levels of proinflammatory cytokines were significantly higher in patient sera compared with control sera. More specifically, the highest levels of tumor necrosis factor-? have been measured in patients presenting "true" HSR, as were the apoptotic markers Fas, caspase 8 activity, and M30. The LTA is sensitive for DILI and SJS/TEN regardless of drug or patient ethnicity. HSR prediction will prevent AED-induced morbidity. In Han Chinese, HLA-B?1502 positivity is a predictor for CBZ-HSR and PHY-HSR. Its negativity does not predict a negative LTG-HSR. There is cross-reactivity between AEDs. Additionally, T-cell cytokines and chemokines control the pathogenesis of SJS/TEN and DILI, contributing to apoptotic processes in the liver and in the skin. PMID:22500513

  9. Positive Selection on Loci Associated with Drug and Alcohol Dependence

    PubMed Central

    Sadler, Brooke; Haller, Gabe; Edenberg, Howard; Tischfield, Jay; Brooks, Andy; Kramer, John; Schuckit, Marc; Nurnberger, John; Goate, Alison

    2015-01-01

    Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima’s D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies. PMID:26270548

  10. Positive clinical neuroscience: explorations in positive neurology.

    PubMed

    Kapur, Narinder; Cole, Jonathan; Manly, Tom; Viskontas, Indre; Ninteman, Aafke; Hasher, Lynn; Pascual-Leone, Alvaro

    2013-08-01

    Disorders of the brain and its sensory organs have traditionally been associated with deficits in movement, perception, cognition, emotion, and behavior. It is increasingly evident, however, that positive phenomena may also occur in such conditions, with implications for the individual, science, medicine, and for society. This article provides a selective review of such positive phenomena--enhanced function after brain lesions, better-than-normal performance in people with sensory loss, creativity associated with neurological disease, and enhanced performance associated with aging. We propose that, akin to the well-established field of positive psychology and the emerging field of positive clinical psychology, the nascent fields of positive neurology and positive neuropsychology offer new avenues to understand brain-behavior relationships, with both theoretical and therapeutic implications. PMID:23286954

  11. Antibiotic-loaded chitosan-Laponite films for local drug delivery by titanium implants: cell proliferation and drug release studies.

    PubMed

    Ordikhani, Farideh; Dehghani, Mehdi; Simchi, Arash

    2015-12-01

    In this study, chitosan-Laponite nanocomposite coatings with bone regenerative potential and controlled drug-release capacity are prepared by electrophoretic deposition technique. The controlled release of a glycopeptide drug, i.e. vancomycin, is attained by the intercalation of the polymer and drug macromolecules into silicate galleries. Fourier-transform infrared spectrometry reveals electrostatic interactions between the charged structure of clay and the amine and hydroxyl groups of chitosan and vancomycin, leading to a complex positively-charged system with high electrophoretic mobility. By applying electric field the charged particles are deposited on the surface of titanium foils and uniform chitosan films containing 25-55 wt% Laponite and 937-1655 µg/cm(2) vancomycin are obtained. Nanocomposite films exhibit improved cell attachment with higher cell viability. Alkaline phosphatase assay reveals enhanced cell proliferation due the gradual dissolution of Laponite particles into the culture medium. In-vitro drug-release studies show lower release rate through a longer period for the nanocomposite compared to pristine chitosan. PMID:26507202

  12. Utah Drug Use Questionnaire.

    ERIC Educational Resources Information Center

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in junior and senior high school students. The 21 multiple choice items pertain to drug use practices, use history, available of drugs, main reason for drug use, and demographic data. The questionnaire is untimed, group administered, and may be given by the classroom teacher in about 10 minutes. Item…

  13. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan Lundine); "Patience and…

  14. Drugs and Young People

    MedlinePLUS

    Drug abuse is a serious public health problem.It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  15. Drug Formulation & Research Profile

    E-print Network

    Giger, Christine

    Drug Formulation & Delivery Research Profile The development of suitable drug formulations and delivery systems remains a major challenge in the full drug pro- duct development and industrialization process. In fact, the effective and safe use of poorly-water soluble drugs such as therapeutic peptides

  16. Incident Type Drug Violation

    E-print Network

    Stowell, Michael

    Traffic Offense Traffic Offense Assist - Medical Assault Drug Violation Drug Violation Drug Violation Drug DR Boulder CO 80302 ILLEGAL POSSESSION OF MARIJUANA Cleared - Summons Date/Time Occured 11/03/2015 23-00002402 11/03/2015 00:04 3300 BASELINE RD Boulder CO 80303 POSSESS NO MORE THAN 2 OZ OF MARIJUANA No Further

  17. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  18. Recovery position - series (image)

    MedlinePLUS

    ... the victim should be placed in the recovery position. The recovery position helps keep the victim's airway open. To put the victim in the recovery position grab the victim's leg and shoulder and roll ...

  19. Black Youths and Illegal Drugs.

    ERIC Educational Resources Information Center

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug

  20. [Drug addiction and cardiovascular pathologies].

    PubMed

    Vandhuick, O; Pistorius, M A; Jousse, S; Ferreira-Maldent, N; Guilmot, J-L; Guias, B; Bressollette, L

    2004-12-01

    Drug addiction which entails cardiovascular risks unknown or misknown to physicians, currently involves an increasing number of miscellaneous drugs, existing in manifold forms. There appears to be no bounds on the way of intake. All territories of the body may be affected with more or less severity. In young people, the cardiac, coronary, cerebral and peripheral vascular systems are generally involved. Two illicit drugs, cannabis and cocaine, showing a permanent increase in misuse, prevail. This drug addiction comes along with intercurrent pathologies which have their own vascular toxicity, especially HIV infection. Moreover, the advent of new illicit substances emphasizes the complexity of the clinical presentations. These complex situations have a real social and medical impact. We are currently in a phase of permanently increasing risk of cardiovascular complications. The pathophysiological mechanisms involved are intertwined and complicated by the frequent association of polytoxicomania or by the effects excipients added to these drugs: direct vascular toxicity, angeitis, arterial and venous thrombosis. Arsenic, a common component of these drugs, is also found in cigarettes; arsenic toxicity mainly affects the lower limbs. Treatment of these complications is non-specific; the ideal solution being weaning which, unfortunately in this peculiar population of patients, may entail serious complications due to the misuse of substitution products. PMID:15738835

  1. Repurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogens

    PubMed Central

    Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N.

    2015-01-01

    Without a doubt, our current antimicrobials are losing the battle in the fight against newly-emerged multidrug-resistant pathogens. There is a pressing, unmet need for novel antimicrobials and novel approaches to develop them; however, it is becoming increasingly difficult and costly to develop new antimicrobials. One strategy to reduce the time and cost associated with antimicrobial innovation is drug repurposing, which is to find new applications outside the scope of the original medical indication of the drug. Ebselen, an organoselenium clinical molecule, possesses potent antimicrobial activity against clinical multidrug-resistant Gram-positive pathogens, including Staphylococcus, Streptococcus, and Enterococcus, but not against Gram-negative pathogens. Moreover, the activity of ebselen against Gram-positive pathogens exceeded those activities determined for vancomycin and linezolid, drugs of choice for treatment of Enterococcus and Staphylococcus infections. The minimum inhibitory concentrations of ebselen at which 90% of clinical isolates of Enterococcus and Staphylococcus were inhibited (MIC90) were found to be 0.5 and 0.25 mg/L, respectively. Ebselen showed significant clearance of intracellular methicillin-resistant S. aureus (MRSA) in comparison to vancomycin and linezolid. We demonstrated that ebselen inhibits the bacterial translation process without affecting mitochondrial biogenesis. Additionally, ebselen was found to exhibit excellent activity in vivo in a Caenorhabditis elegans MRSA-infected whole animal model. Finally, ebselen showed synergistic activities with conventional antimicrobials against MRSA. Taken together, our results demonstrate that ebselen, with its potent antimicrobial activity and safety profiles, can be potentially used to treat multidrug resistant Gram-positive bacterial infections alone or in combination with other antibiotics and should be further clinically evaluated. PMID:26222252

  2. Drug interaction management.

    PubMed

    Hansten, Philip D

    2003-06-01

    Although thousands of articles on drug interactions have been published and numerous computerized screening systems have been developed, patients continue to suffer from adverse drug interactions. Possible methods for reducing the risk of drug interactions include improving the knowledge of health care providers, improving computerized screening systems, providing information on patient risk factors, increased use of pharmacogenetic information, more attention to drug administration risk factors, and improving patient education on drug interactions. PMID:12840961

  3. Public Policy Foundations for Positive Behavioral Interventions, Strategies, and Supports

    E-print Network

    Turnbull, H. Rutherford; Wilcox, Brennan L.; Stowe, Matthew J.; Carolyn, Raper; Hedges, Laura Penny

    2000-01-01

    greater leeway in choosing an intervention/treatment than when it deals with a minor in its school system. Consistent with good professional practice, it may offer positive interventions, electro-convulsive shock treatment, or psychotropic drug regimens... greater leeway in choosing an intervention/treatment than when it deals with a minor in its school system. Consistent with good professional practice, it may offer positive interventions, electro-convulsive shock treatment, or psychotropic drug regimens...

  4. 11. CALIFORNIATYPE DEPRESSION BEAM: Photocopy of photograph showing a Californiatype ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. CALIFORNIA-TYPE DEPRESSION BEAM: Photocopy of photograph showing a California-type depression beam positioned in its yokes. A car would approach the beam moving towards the camera. Note the open access cover, pulleys, counterweight hatchcover, and the wooden construction of the beam. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  5. 41. VIEW LOOKING IN TANK, SHOWING TRAINING DURING ASCENT (WEARING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. VIEW LOOKING IN TANK, SHOWING TRAINING DURING ASCENT (WEARING STEINKE HOOD) AT RIGHT, DIVING INSTRUCTOR AT LEFT MAINTAINING HIS POSITION ON THE WIRE No date - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  6. 72. View of test system showing Klystron tube installed in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    72. View of test system showing Klystron tube installed in test position on first floor of transmitter building no. 102. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

  7. 5. FLOOR 3; SHOWS BRAKE LEVER, BLOCK FORMERLY USED TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. FLOOR 3; SHOWS BRAKE LEVER, BLOCK FORMERLY USED TO RAISE IT AND HOOK WHICH KEPT IT IN THE 'OFF' POSITION; ALSO SEEN ARE THE LARGE BLOCKS SUSPENDED FROM THE CAP FRAME WHICH HOLD THE TRUCK WHEELS TO CENTER THE CAP - Hayground Windmill, Windmill Lane, East Hampton, Suffolk County, NY

  8. Psychedelic Drug Flashbacks: Psychotic Manifestation or Imaginative Role Playing?

    ERIC Educational Resources Information Center

    Matefy, Robert E.; Krall, Roger

    1975-01-01

    Examines possible differences in psychopathological characteristics among flashbackers, nonflashback drug users, and nondrug user controls. Results indicate that flashbackers show no more general maladjustment than the nonflashback drug users. (Author)

  9. Mining drug-disease relationships as a complement to medical genetics-based drug repositioning: Where a recommendation system meets genome-wide association studies.

    PubMed

    Wang, H; Gu, Q; Wei, J; Cao, Z; Liu, Q

    2015-05-01

    A novel recommendation-based drug repositioning strategy is presented to simultaneously determine novel drug indications and side effects in one integrated framework. This strategy provides a complementary method to medical genetics-based drug repositioning, which reduces the occurrence of false positives in medical genetics-based drug repositioning, resulting in a ranked list of new candidate indications and/or side effects with different confidence levels. Several new drug indications and side effects are reported with high prediction confidences. PMID:25670647

  10. Want Positive Behavior? Use Positive Language

    ERIC Educational Resources Information Center

    Wood, Chip; Freeman-Loftis, Babs

    2012-01-01

    Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

  11. Positive Classroom Environments = Positive Academic Results

    ERIC Educational Resources Information Center

    Wilson-Fleming, LaTerra; Wilson-Younger, Dylinda

    2012-01-01

    This article discusses the effects of a positive classroom environment and its impact on student behavior and achievement. It also provides strategies for developing expectations for student achievement and the importance of parental involvement. A positive classroom environment is essential in keeping behavior problems to a minimum. There are a…

  12. Positive Education: Positive Psychology and Classroom Interventions

    ERIC Educational Resources Information Center

    Seligman, Martin E. P.; Ernst, Randal M.; Gillham, Jane; Reivich, Karen; Linkins, Mark

    2009-01-01

    Positive education is defined as education for both traditional skills and for happiness. The high prevalence worldwide of depression among young people, the small rise in life satisfaction, and the synergy between learning and positive emotion all argue that the skills for happiness should be taught in school. There is substantial evidence from…

  13. The relationship of drug use to denture function and saliva flow rate in a geriatric population.

    PubMed

    Kreher, J M; Graser, G N; Handelman, S L

    1987-05-01

    This study investigated an "old elderly" population and the relationships between the use of hyposalivatory drugs and denture function, including saliva flow rates and denture-supporting structures and health. There was a high prevalence of drug use and medical problems. Hyposalivatory drugs were prescribed for more than half of the subjects. There was a significant relationship between increased hyposalivatory drug use and reduced saliva flow rates. Reduced values for denture-supporting structures were found to be related to increased medical problems and hyposalivatory drug use. Reduced values for denture-supporting tissue health were found to be related to masticatory performance and retention and stability. Bite force showed a strong positive relationship with masticatory performance. Some of the subjective evaluations by the subjects showed statistically significant relationship with their respective objective measures: perceptions of dry mouth were related to saliva flow rates, perceptions of denture rocking or looseness were related to retention and stability ratings, and reports of pain on chewing were related to masticatory performance. It may be concluded that the use of drugs with hyposalivatory side effects may have a deleterious influence on the denture-bearing tissue. Direct influence on denture function, however, was not found. These findings provide valuable insights into the effects of drug usage in old age and their impact on oral health and denture function. Diagnostic and treatment capabilities are thus enhanced in that physicians, pharmacists, and other health-related professionals can be alerted to the problems accompanying hyposalivatory drug use. This may permit alternatives in medication when possible, and dentists may more effectively plan and conduct prosthodontic care for these individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3298631

  14. New England 4-H Horse Show

    E-print Network

    New Hampshire, University of

    New England 4-H Horse Show Rules and Guidelines Basic guide to local, county, and state/regional 4-H Horse shows as well as for those classes in open shows limited to 4-H membership entry. This rules-H Rule Book Page 2 Revised April 2014 All revisions of the New England 4-H Horse Show Rules

  15. Ovarian Cancer Drug Shows Promise with Tough-To-Treat Prostate Tumors

    MedlinePLUS

    ... rights reserved. More Health News on: Genes and Gene Therapy Prostate Cancer Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Prostate Cancer About MedlinePlus Site Map FAQs Contact ...

  16. Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistance.

    PubMed

    Bhardwaj, Ashima K; Vinothkumar, Kittappa; Rajpara, Neha

    2013-04-01

    Quorum sensing (QS) is a bacterial communication process that depends on the bacterial population density. It involves small diffusible signaling molecules which activate the expression of myriad genes that control diverse array of functions like bioluminescence, virulence, biofilm formation, sporulation, to name a few. Since QS is responsible for virulence in the clinically relevant bacteria, inhibition of QS appears to be a promising strategy to control these pathogenic bacteria. With indiscriminate use of antibiotics, there has been an alarming increase in the number of antibiotic resistant pathogens. Antibiotics are no longer the magic bullets they were once thought to be and therefore there is a need for development of new antibiotics and/or other novel strategies to combat the infections caused by multidrug resistant organisms. Quorum sensing inhibition or quorum quenching has been pursued as one of such novel strategies. While antibiotics kill or slow down the growth of bacteria, quorum sensing inhibitors (QSIs) or quorum quenchers (QQs) attenuate bacterial virulence. A large body of work on QS has been carried out in deadly pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio fischeri, V. harveyi, Escherichia coli and V. cholerae etc to unravel the mechanisms of QS as well as identify and study QSIs. This review describes various aspects of QS, QSI, different model systems to study these phenomena and recent patents on various QSIs. It suggests QSIs as attractive alternatives for controlling human, animal and plant pathogens and their utility in agriculture and other industries. PMID:23394143

  17. Drug-induced esophageal strictures.

    PubMed Central

    Bonavina, L; DeMeester, T R; McChesney, L; Schwizer, W; Albertucci, M; Bailey, R T

    1987-01-01

    A retrospective study of 55 patients with a benign esophageal stricture showed that in 11 patients (20%) the cause was a drug-induced lesion due to potassium chloride (3), tetracyclines (3), aspirin (2), vitamin C (1), phenytoin (1), and quinidine (1). Five of the 11 patients would have been diagnosed as having a reflux etiology of their stricture if 24-hour esophageal pH monitoring was not performed. Six patients responded to dilatation and five patients required resection or bypass. A prospective study of 18 asymptomatic volunteers showed a high incidence of esophageal lodgment of a radiolabeled medicinal capsule, with subsequent dissolution and release of the isotope. This occurred most frequently in elderly subjects and was reduced by increasing the volume of water chaser. The sites of lodgment correspond to the location of the observed strictures in the patient population. An in vitro study showed that, when the causative drugs were mixed with saliva, dissolution occurred within 60 minutes and was associated with significant changes in pH. These investigations show that drug-induced esophageal strictures are more common than previously appreciated, and can be confused with a reflux etiology. Diagnosis is suggested by a history of drug ingestion, location of the stricture, and a normal esophageal acid exposure on 24-hour pH monitoring. The severity of the esophageal injury is variable and requires dilatation to resection for therapy. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:3606243

  18. Case management in a DUI lab: effect on drugs reported.

    PubMed

    Tiscione, Nicholas B; Shan, Xiaoqin; Yeatman, Dustin Tate

    2014-10-01

    An evaluation of an internal laboratory decision to implement a protocol for limiting drug testing based on ethanol concentration in laboratory analysis for driving under the influence (DUI) cases is presented. The described case management strategy is supported by known impairment of ethanol at relatively high concentrations, difficulty assigning a level of contributing impairment from drugs in the presence of high ethanol levels and the likelihood that the drug results may be suppressed at trial. Although the results of this study reinforce the assertion that such protocols lead to the under reporting of drugs in DUI cases, for the majority of cases, 95% in this study, the drug analysis results were not significant and did not warrant the time and resources needed for the additional blood drug testing. Furthermore, the study demonstrated that a high drug positivity rate does not necessarily mean that those drug results are legally or pharmacologically meaningful. Additional research should be conducted with quantitative drug results and casework impact of blood drug screen protocols as previous studies only report drug positivity rates and not whether the drug results would be meaningful to the case. PMID:25217546

  19. 21 CFR 250.102 - Drug preparations intended for human use containing certain “coronary vasodilators”.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... substantial evidence of effectiveness nor a general recognition by qualified experts that such drugs are... a new-drug application based on a showing of safety and effectiveness. (d) Any such drug in...

  20. Toward a Rational View of Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    McGlothlin, William H.

    The enactment of California's "LSD Bill" is presented as an example of poor judgment in drug legislation on the state level. An appraisal of the nonmedical use of hallucinogens centering around the types of users, and the results of drug use, shows that the principal social impact of hallucinogens is on the personalities and values of the users.…

  1. Drugs and Personality: Extraversion-Introversion.

    ERIC Educational Resources Information Center

    Spotts, James V.; Shontz, Franklin C.

    1984-01-01

    Administered the Eysenck Personality Inventory as part of a larger battery of tests to chronic users of drugs (N=43) to determine how drug use influences personality. Results showed that cocaine and opiates users were more introverted; and amphetamine users, barbiturates users and nonusers were more extraverted. (LLL)

  2. Position: Date UMCES Location

    E-print Network

    Boynton, Walter R.

    Position: Date UMCES Location: Lab Director or PI: 1. Advertising Media: A. Publication Date Date B: Position must be listed with MD State Employment Security Administration Location Date Date 2. Male Female for position 4. Applicant selected for position: Race/Ethnic Category _______; Gender-Male______, Female

  3. Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to antituberculosis drugs.

    PubMed

    Sun, Qin; Sha, Wei; Gui, Xu-Wei; Xiao, Yang-Jiong; Zeng, Wei-Hong; Sun, Wen-Wen; Xiao, He-Ping; Ye, Wei-Yi

    2015-06-01

    Antituberculosis (TB) chemotherapeutic drugs may cause a variety of adverse drug reactions (ADRs). To assess the potential of drug-induced lymphocyte stimulation test (DLST) in screening ADRs in patients treated with anti-TB drugs, we performed DLST in 272 TB patients (176 cases with ADRs and 96 controls without ADRs) treated with anti-TB drugs isoniazid (INH), rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA). The ADRs were diagnosed by drug provocation test based on clinical and laboratory examinations. The sensitivities of DLST in the diagnosis of INH-, RFP-, EMB-, or PZA-induced ADRs were 57.8%, 37.1%, 42.4%, and 23.1%, respectively, with the corresponding specificities being 93.4%, 94.0%, 97.5%, and 98.8%. DLST has high specificity and limited sensitivity in the diagnosis of anti-TB drug-induced ADRs. In combination with clinical observation and drug use history, DLST could have a predictive validity of ADRs, especially when a positive result is obtained. PMID:25863530

  4. A cutaneous positioning system.

    PubMed

    Martin, Bernard J; Lee, Beom-Chan; Sienko, Kathleen H

    2015-04-01

    Our previous work revealed that torso cutaneous information contributes to the internal representation of the torso and plays a role in postural control. Hence, the aims of this study were to assess whether posture could be manipulated by patterns of vibrotactile stimulation and to determine whether resulting modified postures were associated with specific and consistent spatial attitudes. Ten healthy young adults stood in normal and Romberg stances with six vibrating actuators positioned on the torso in contact with the skin over the anatomical locations corresponding to left and right external oblique, internal oblique and erector spinae muscles at the L4/L5 vertebrae level. A 250-Hz tactile vibration was applied for 5 s either at a single location or consecutively at each location in clockwise or counterclockwise sequences. Kinematic analysis of the body segments indicated that postural responses observed in response to single and sequential stimulation patterns were similar, while the center of pressure remained unaltered in any situations. Moreover, torso inclinations followed rectilinear-like path segments chartered by stimuli loci during sequential stimulations. Comparison of torso attitudes with previous results obtained with co-vibration patterns of the same duration showed that torso inclination amplitudes are equivalent for single (one location) and co-vibration (pairs of locations) patterns inducing the same directional effect. Hence, torso cutaneous information exhibits kinesthetic properties, appears to provide a map of upper body spatial configuration, and could assume the role of an internal positioning system for the upper body. PMID:25600816

  5. 76 FR 47594 - National Institutes of Health; Proposed Collection; Comment Request; Simulations for Drug Related...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ...evaluation seeks to determine whether the multimedia module Archie MD: The Science of Drugs (1) Increases students' knowledge in brain and heart biology and the effects drugs have on the body (2) Increases positive attitudes towards science education for...

  6. Scientific issues in drug testing: council on scientific affairs

    SciTech Connect

    Not Available

    1987-06-12

    Testing for drugs in biologic fluids, especially urine, is a practice that has become widespread. The technology of testing for drugs in urine has greatly improved in recent years. Inexpensive screening techniques are not sufficiently accurate for forensic testing standards, which must be met wihen a person's employment or reputation may be affected by results. This is particularly a concern during screening of a population in which the prevalence of drug use is very low, in which the predictive value of a positive result would be quite low. Physicians should be aware that results from drug testing can yield accurate evidence of prior exposure to drugs, but they do not provide information about patterns of drug use, about abuse of or dependence on drugs, or about mental or physical impairments that may result from drug use.

  7. Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery

    PubMed Central

    Chaiyasan, Wanachat; Srinivas, Sangly P.

    2015-01-01

    Purpose To examine the benefits of chitosan-dextran sulfate nanoparticles (CDNs) as a topical ocular delivery system with lutein as a model drug. Methods CDNs were developed by polyelectrolyte complexation of positively charged chitosan (CS) and negatively charged dextran sulfate (DS). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and polyethylene glycol 400 (PEG400) were used as co-crosslinking and stabilizing agents, respectively. The influence of these on the properties of CDNs, including drug release and mucoadhesiveness, was examined. The chemical stability of lutein in CDNs (LCDNs) was also examined. Results Typically, LCDNs showed a spherical shape, possessing a mean size of ~400 nm with a narrow size distribution. The entrapment efficiency of lutein was in the range of 60%–76%. LCDNs possessing a positive surface charge (+46 mV) were found to be mucoadhesive. The release profile of LCDNs followed Higuchi’s square root model, suggesting drug release by diffusion from the polymer matrix. Lutein in LCDNs showed increased chemical stability during storage compared to its solution form. Conclusions These characteristics of CDNs make them suitable for drug delivery to the ocular surface. PMID:26604662

  8. Sample positioning in microgravity

    NASA Technical Reports Server (NTRS)

    Sridharan, Govind (inventor)

    1993-01-01

    Repulsion forces arising from laser beams are provided to produce mild positioning forces on a sample in microgravity vacuum environments. The system of the preferred embodiment positions samples using a plurality of pulsed lasers providing opposing repulsion forces. The lasers are positioned around the periphery of a confinement area and expanded to create a confinement zone. The grouped laser configuration, in coordination with position sensing devices, creates a feedback servo whereby stable position control of a sample within microgravity environment can be achieved.

  9. Sample positioning in microgravity

    NASA Technical Reports Server (NTRS)

    Sridharan, Govind (inventor)

    1991-01-01

    Repulsion forces arising from laser beams are provided to produce mild positioning forces on a sample in microgravity vacuum environments. The system of the preferred embodiment positions samples using a plurality of pulsed lasers providing opposing repulsion forces. The lasers are positioned around the periphery of a confinement area and expanded to create a confinement zone. The grouped laser configuration, in coordination with position sensing devices, creates a feedback servo whereby stable position control of a sample within microgravity environment can be achieved.

  10. Doctors, drugs, and the FDA.

    PubMed

    Shanklin, D R

    1972-11-01

    This communication is directed to obstetricians, to the Food and Drug Administration (FDA), and to those individuals who might want to impose possibly unnecessary external structures on the practice of medicine. It is considered a positive that the patients of today are well informed and are more actively participating in therapeutic design. There is more veto power on the part of the patient and more concern over the trained ability of the physician. In the past physicians frequently made judgements individually, applying isolated and at times random standards for their decisions. Such actions were inevitable in an era when neither pathogenesis nor treatment was well understood. Now there is no excuse for such actions. Communication is easy, journals are widely circulated, and there are numerous refresher seminars. Increased specialization of knowledge has meant more corporate or group decisions for therapy. Current trends will continue to offer both opportunities and responsibilities. The opportunities are for better diffusion of knowledge, and the responsibility is to be informed. There can be a high level national standard for medical practice. As a beginning, the medical practice laws could use some uniform decisions. The FDA needs to show more responsiveness to changing knowledge and increased willingness to reconsider indications and contraindications in the light of newer experience. There is sufficient information available now to support the revocation of the approval of the use of diuretics in the management of human pregnancy. Another role of the FDA is the approval of new substances or new uses of old substances. The prostaglandins appear in this category, and the December 1972 issue will include the recent Brook Lodge Symposium on prostaglandins. The individual physician requires journal articles, individual experience, and designed trials in order to make judgements on patients who may have some factors not accounted for by groupthink or regulations. PMID:4634511

  11. The malleable effect of name fluency on pharmaceutical drug perception.

    PubMed

    Cho, Hyejeung

    2015-10-01

    Based on the fluency theory, a recent study by Dohle and Siegrist revealed that complex pharmaceutical drug names are perceived as more hazardous than simple drug names and thus negatively influence patients' willingness to buy. This study explored the malleability of the name fluency effect on pharmaceutical drug perception by examining the fluency effect in the domain of risk versus advancedness judgment. The findings indicated that depending on how the fluency feeling is interpreted in the context of initial judgment task (e.g. advancedness vs risk), disfluent drug names can positively influence a patient's perception of the drug, reversing the typical fluency effect. PMID:24677431

  12. Rhythmomimetic drug delivery

    E-print Network

    M. Carme Calderer; Yoichiro Mori; Ronald A. Siegel; Lingxing Yao

    2015-01-06

    We present modeling, analysis and numerical simulation of a prototype glucose driven drug delivery device based on chemomechanical interactions and volume phase transitions in polyelectrolyte gels. The device consists of two fluid compartments, an external cell (I) mimicking the physiological environment, and a closed chamber (II), separated by a hydrogel membrane. Cell I, which is held at constant pH and ionic strength, provides a constant supply of glucose to cell II, and also serves as clearance station for reaction products. Cell II contains the drug to be delivered to the body, an enzyme that catalyzes conversion of glucose into hydrogen ions, and a piece of marble to remove excess hydrogen ions that would otherwise overwhelm the system. When the membrane is swollen, glucose flux into Cell II is high, leading to rapid production of hydrogen ions. However, the hydrogen ions are not immediately released to Cell I but react, instead, with the negatively charged carboxyl groups of the membrane, which collapses when a critical pH is reached in Cell II, substantially attenuating glucose transport and $\\textrm {H}^+$ production. Subsequent diffusion of attached $\\textrm {H}^+$ ions increases again the concentration of negative carboxyl groups in the membrane, causing the gel to re-swell, and the process is poised to repeat itself. Since drug release can only occur when the membrane is swollen, release occurs in rhythmic pulses that are coherent with the pH oscillations in Cell II and swelling oscillations of the membrane. The work to analyze them combines multiscale methods with tools from dynamical systems to show existence of sustained oscillations for a robust set of material parameters. The predictions of the model are in good agreement with earlier experimental results obtained with a laboratory device.

  13. Assessment of drug delivery devices.

    PubMed

    Batista, Elsa; Almeida, Nelson; Furtado, Andreia; Filipe, Eduarda; Sousa, Luis; Martins, Rui; Lucas, Peter; Petter, Harm Tido; Snijder, Roland; Timmerman, Annemoon

    2015-08-01

    For critical drug delivery, it is important to have a constant and well-known infusion rate delivered by the complete infusion set-up (pump, tubing, and accessories). Therefore, various drug delivery devices and accessories were tested in this article in terms of their infusion accuracy, start-up delay, response time, and dependency on the viscosity. These measurements were performed as part of the European funded research project MeDD. The obtained results show that the infusion accuracy of the devices is flow rate and accessory depended, especially for low flow rates. Viscosity does not have a significant impact on the flow rate accuracy. PMID:25945719

  14. Adverse drug events in hospital: pilot study with trigger tool

    PubMed Central

    Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia

    2013-01-01

    OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension. PMID:24626548

  15. Capillary electrophoresis for drug analysis

    NASA Astrophysics Data System (ADS)

    Lurie, Ira S.

    1999-02-01

    Capillary electrophoresis (CE) is a high resolution separation technique which is amenable to a wide variety of solutes, including compounds which are thermally degradable, non-volatile and highly polar, and is therefore well suited for drug analysis. Techniques which have been used in our laboratory include electrokinetic chromatography (ECC), free zone electrophoresis (CZE) and capillary electrochromatography (CEC). ECC, which uses a charged run buffer additive which migrates counter to osmotic flow, is excellent for many applications, including, drug screening and analyses of heroin, cocaine and methamphetamine samples. ECC approaches include the use of micelles and charged cyclodextrins, which allow for the separation of complex mixtures. Simultaneous separation of acidic, neutral and basic solutes and the resolution of optical isomers and positional isomers are possible. CZE has been used for the analysis of small ions (cations and anions) in heroin exhibits. For the ECC and CZE experiments performed in our laboratory, uncoated capillaries were used. In contrast, CEC uses capillaries packed with high performance liquid chromatography stationary phases, and offers both high peak capacities and unique selectivities. Applications include the analysis of cannabinoids and drug screening. Although CE suffers from limited concentration sensitivity, it is still applicable to trace analysis of drug samples, especially when using injection techniques such as stacking, or detection schemes such as laser induced fluorescence and extended pathlength UV.

  16. Phenotypic drug profiling in droplet microfluidics for better targeting of drug-resistant tumors

    PubMed Central

    Sarkar, S.; Cohen, N.; Sabhachandani, P.; Konry, T.

    2015-01-01

    Acquired drug resistance is a key factor in the failure of chemotherapy. Due to intratumoral heterogeneity, cancer cells depict variations in intracellular drug uptake and efflux at the single cell level, which may not be detectable in bulk assays. In this study we present a droplet microfluidics-based approach to assess the dynamics of drug uptake, efflux and cytotoxicity in drug-sensitive and drug-resistant breast cancer cells. An integrated droplet generation and docking microarray was utilized to encapsulate single cells as well as homotypic cell aggregates. Drug-sensitive cells showed greater death in the presence or absence of Doxorubicin (Dox) compared to the drug-resistant cells. We observed heterogeneous Dox uptake in individual drug-sensitive cells while the drug-resistant cells showed uniformly low uptake and retention. Dox-resistant cells were classified into distinct subsets based on their efflux properties. Cells that showed longer retention of extracellular reagents also demonstrated maximal death. We further observed homotypic fusion of both cell types in droplets, which resulted in increased cell survival in the presence of high doses of Dox. Our results establish the applicability of this microfluidic platform for quantitative drug screening in single cells and multicellular interactions. PMID:26456240

  17. UV Photography Shows Hidden Sun Damage

    MedlinePLUS

    ... skin UV photography shows hidden sun damage UV photography shows hidden sun damage A UV photograph gives ... developing skin cancer and prematurely aged skin. Normal photography UV photography 18 months of age: This boy's ...

  18. New Hampshire Guide 4H Dog Shows

    E-print Network

    New Hampshire, University of

    New Hampshire Guide to 4H Dog Shows UNH Cooperative Extension 4H Youth ................................................................................................................................. 2 Purpose of the 4H Dog Project ................................................................................................................ 2 4H DOG SHOW GENERAL INFORMATION

  19. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions." PMID:16412107

  20. Antiplatelet and Anticoagulant Drugs in Interventional Radiology

    SciTech Connect

    Altenburg, Alexander; Haage, Patrick

    2012-02-15

    In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

  1. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  2. Position: Residence Hall Director POSITION ANNOUNCEMENT NO.

    E-print Network

    Huang, Jianyu

    -of-the-art facilities and the Schmeeckle Nature Reserve. The university has a strong focus on sustainability initiatives - Ability to develop and nurture a positive community living environment in the residence halls Appointment

  3. Association between auditory P300, psychopathology, and memory function in drug-naïve schizophrenia.

    PubMed

    Chang, Wei-Hung; Chen, Kao-Chin; Yang, Yen-Kuang; Chen, Po-See; Lu, Ru-Band; Yeh, Tzung-Lieh; Wang, Carol Sheei-Meei; Lee, I-Hui

    2014-03-01

    The aim of this study was to explore memory deficits and psychopathology and their relationships with P300 in drug-naïve patients with schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Wechsler Memory Scale-Revised were administered. Auditory event-related potentials elicited by an oddball paradigm were obtained. After controlling for age, sex, the results showed a statistically significant negative correlation between the total PANSS score and P300 amplitude at the parietal position (r = -0.66, p < 0.05). Moreover, visual memory was significantly positively correlated with P300 amplitude at the parietal position (r = 0.67, p < 0.05). After controlling for the duration of illness, the above correlations remained statistically significant. The correlation between P300 and the severity of psychopathology was reconfirmed in drug-naïve patients with schizophrenia. A possible contribution of memory decompensation in P300 among drug-naïve patients with schizophrenia may be considered, and the compensatory or Default Model Network might be a possible explanation of this association. PMID:24581213

  4. The relationship between drug use stigma and HIV injection risk behaviors among injection drug users in Chennai, India

    PubMed Central

    Latkin, Carl; Srikrishnan, Aylur K; Yang, Cui; Johnson, Sethulakshmi; Solomon, Sunil S; Kumar, Suresh; Celentano, David D; Solomon, Suniti

    2011-01-01

    Background The purpose of this study was to examine the relationship between perceived drug use stigma, acquiescence response bias, and HIV injection risk behaviors among current injection drug users in Chennai, India. Methods The sample consists of 851 males in Chennai, India who reported having injected drugs in the last month and were recruited through street outreach. Results Results indicate a strong and consistent positive association between drug use stigma and HIV injection drug use risk behaviors. This association held across the injection behaviors of frequency of sharing needles, cookers, cotton filters, rinse water, prefilled syringes and common drug solutions, even after controlling for acquiescence response bias, frequency of injection, and HIV/HCV serostatus. Conclusions These findings suggest that future HIV prevention and harm reduction programs for injection drug users and service providers should address drug use stigma. PMID:20462707

  5. Hardcore drug users claim to be occasional users: drug use frequency underreporting.

    PubMed

    Morral, A R; McCaffrey, D; Iguchi, M Y

    2000-01-01

    Self-reports of drug use frequency are central to treatment outcome evaluations, estimates of the prevalence of heavy use, estimates of treatment need, and other questions with direct relevance to drug policies. Nevertheless, surprisingly little is known about the validity of these self-reports. This study examines the accuracy of 701 frequency self-reports made by a sample of methadone maintenance clients. Self-report accuracy is evaluated by comparing rates of positive urinalyses found for each case with rates that would be expected had drug use occurred only as often as reported. Expected rates of positive urinalyses are derived from conservative Monte Carlo models of drug use for each case. This procedure reveals extensive heroin and cocaine use frequency underreporting. After adjusting for frequency underreporting, 51% of 279 cases reporting only occasional heroin use (1-10 days in the past 30), and 22% of the 157 cases reporting occasional cocaine use, are found to be using these drugs with frequencies corresponding to what the Office of National Drug Control Policy defines as 'hardcore use' (more than 10 days in the past 30). Drug use frequency underreporting appears substantial, and might constitute an important threat to the validity of some treatment outcome evaluations, needs assessments and other analyses that rely on drug use frequency self-reports. PMID:10661670

  6. POSITION OPENING Position Title: Postdoctoral Position in Complexity Science

    E-print Network

    Suresh, Subra

    , social media, public transport e-ticket records and taxi movements among others. JOB DESCRIPTION for exceptional candidates to fill a postdoctoral position for the modeling and analysis of complex urban systems able to model their dynamics and create innovative solutions for improving urban life. The available

  7. Drug Design and Emotion

    NASA Astrophysics Data System (ADS)

    Folkers, Gerd; Wittwer, Amrei

    2007-11-01

    "Geteiltes Leid ist halbes Leid." The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. Though subjective, mental and physical states can be shared. Visual perception of suffering may be important but also narrative description plays a role, all our senses are mixing in. It is hypothetized that literature, art and humanities allow this overlap. A change of mental states can lead to empirically observable effects as it is the case for the effect of role identity or placebo on pain perception. Antidepressants and other therapeutics are another choice to change the mental and bodily states. Their development follows today's notion of "rationality" in the design of therapeutics and is characterized solely by an atomic resolution approach to understand drug activity. Since emotional states and physiological states are entangled, given the difficulty of a physical description of emotion, the future rational drug design should encompass mental states as well.

  8. Melatonergic drugs in development

    PubMed Central

    Carocci, Alessia; Catalano, Alessia; Sinicropi, Maria Stefania

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is widely known as “the darkness hormone”. It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review. PMID:25258560

  9. Multi-image position detection.

    PubMed

    Haist, Tobias; Dong, Shihao; Arnold, Thomas; Gronle, Mark; Osten, Wolfgang

    2014-06-16

    The exact measurement of positions is of fundamental importance in a multitude of image-sensor based optical measurement systems. We propose a new method for enhancing the accuracy of image-sensor based optical measurement systems by using a computer-generated hologram in front of the imaging system. Thereby, the measurement spot is replicated to a predefined pattern. Given enough light to correctly expose the sensor, the position detection accuracy can be considerably improved compared to the conventional one-spot approach. For the evaluation of the spot position we used center-of-gravity based averaging. We present simulated as well as experimental results showing an improvement by a factor of 3.6 to a positioning accuracy of better than three thousandths of a pixel for a standard industrial CCD sensor. PMID:24977542

  10. Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain

    PubMed Central

    Webster, J Christopher; Francis, Michael M; Porter, Julia K; Robinson, Gillian; Stokes, Clare; Horenstein, Ben; Papke, Roger L

    1999-01-01

    We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function.The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine.Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage.Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field.An analysis of point mutations indicates that the residues at the 6? position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10? position are not sufficient to produce effects, but 6? 10? double mutants show more effect than do the 6? single mutants. PMID:10455283

  11. Teratogenic effects of antiepileptic drugs

    PubMed Central

    Hill, Denise S; Wlodarczyk, Bogdan J; Palacios, Ana M; Finnell, Richard H

    2010-01-01

    Many antiepileptic drugs (AEDs) have therapeutic applications that extend beyond epilepsy to include neuropathic pain, migraine headaches and psychiatric disorders. The risk of some AEDs has been clearly established, but for newer drugs, small sample sizes and polytherapy exposures preclude a conclusive determination of their teratogenic potential. Most women with epilepsy will require AED therapy throughout their entire pregnancy to control seizures; the vast majority of pregnancies in women with epilepsy have positive outcomes. A conservative estimate suggests that AED monotherapy doubles, and polytherapy triples, the risk for major congenital malformations. Furthermore, while evidence is still accruing, recent investigations suggest that exposure to select AEDs results in altered cognitive function later in development. There is no evidence to suggest that additional folic acid supplementation ameliorates the increased risk of congenital malformations conferred by in utero AED exposure. PMID:20518610

  12. National Drug IQ Challenge

    MedlinePLUS

    ... Heads Up: Real News About Drugs and Your Body Mind Over Matter Series Blog Teaching Guide Explorando la ... Heads Up: Real News About Drugs and Your Body Mind Over Matter Series Blog Teaching Guide Explorando la ...

  13. Neuropathy secondary to drugs

    MedlinePLUS

    Neuropathy secondary to drugs is a loss of sensation or movement in a part of the body ... weakness. Many medicines may affect the development of neuropathy, including: Heart or blood pressure drugs: Amiodarone Hydralazine ...

  14. Access to Investigational Drugs

    Cancer.gov

    A fact sheet that defines investigational drugs (drugs under study but not yet FDA approved) and describes the special conditions under which patients and their doctors can apply to receive these treatments.

  15. Understanding the Drug Menace

    ERIC Educational Resources Information Center

    Cooper, Donald L.

    1972-01-01

    Understanding how drugs affect cerebral pleasure centers is important in knowing how to combat the drug problem. The author advocates more effective health education for the purpose of engendering respect for the body. (Editor)

  16. Prescription Drug Abuse

    MedlinePLUS

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include narcotic painkillers, ...

  17. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process. PMID:25912018

  18. Prescription Drug Abuse

    MedlinePLUS

    ... Abused Drugs Charts Emerging Trends Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... and by 2007, outnumbered those involving heroin and cocaine. NIDA hopes to change this situation by increasing ...

  19. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  20. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  1. Adolescent drug abuse - Awareness & prevention

    E-print Network

    Chakravarthy, Bharath; Shah, Shyam; Lotfipour, Shahram

    2013-01-01

    and the treatment of drug addiction creates a tremendouspredisposition towards drug addiction; A retrospective studyaddiction. The study demonstrated that each additional ACE increased the likelihood for drug

  2. Adolescent drug abuse - Awareness & prevention

    E-print Network

    Chakravarthy, Bharath; Shah, Shyam; Lotfipour, Shahram

    2013-01-01

    and the treatment of drug addiction creates a tremendouspredisposition towards drug addiction 4 . A retrospectiveaddiction. The study demonstrated that each additional ACE increased the likelihood for drug

  3. Targeted drug induces responses in aggressive lymphomas

    Cancer.gov

    Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.

  4. Dendrimer-based nanocarriers demonstrating a high efficiency for loading and releasing anticancer drugs against cancer cells in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Quyen Tran, Ngoc; Khoa Nguyen, Cuu; Phuong Nguyen, Thi

    2013-12-01

    Dendrimer, a new class of hyper-branched polymer with predetermined molecular weight and well-controlled size, has received much attention in nanobiomedical applications such as drug carrier, gene therapy, disease diagnosis, etc. In this study, pegylated polyamidoamine (PAMAM) dendrimer at generation 3.0 (G 3.0) and carboxylated PAMAM dendrimer G 2.5 were prepared for loading anticancer drugs. For loading cisplatin, carboxylated dendrimer could carry 26.64 wt/wt% of cisplatin. The nanocomplexes have size ranging from 10 to 30 nm in diameter. The drug nanocarrier showed activity against NCI-H460 lung cancer cell line with half maximal inhibitory (IC50) of 23.11 ± 2.08 ?g ml-1. Pegylated PAMAM dendrimers (G 3.0) were synthesized below 40 nm in diameter for carrying 5-fluorouracil (5-FU). For 5-FU encapsulation, pegylated dendrimer showed a high drug-loading efficiency of the drug and a slow release profile of 5-FU. The drug nanocarrier system exhibited an antiproliferative activity against MCF-7 cells (breast cancer cell) with a half maximal inhibitory (IC50) of 9.92 ± 0.19 ?g ml-1. In vivo tumor xenograft study showed that the 5-FU encapsulated pegylation of dendrimer exhibited a significant decrement in volume of tumor which was generated by MCF-7 cancer cells. These positive results from our studies could pave the ways for further research of drugs dendrimer nanocarriers toward cancer chemotherapy.

  5. Stigma, social reciprocity and exclusion of HIV/AIDS patients with illicit drug histories: A study of Thai nurses' attitudes

    PubMed Central

    Chan, Kit Yee; Stoové, Mark A; Reidpath, Daniel D

    2008-01-01

    Background Stigma is a key barrier for the delivery of care to patients living with HIV/AIDS (PLWHA). In the Asia region, the HIV/AIDS epidemic has disproportionately affected socially marginalised groups, in particular, injecting drug users. The effect of the stigmatising attitudes towards injecting drug users on perceptions of PLWHA within the health care contexts has not been thoroughly explored, and typically neglected in terms of stigma intervention. Methods Semi-structured interviews were conducted with a group of twenty Thai trainee and qualified nurses. Drawing upon the idea of 'social reciprocity', this paper examines the constructions of injecting drug users and PLWHA by a group of Thai nurses. Narratives were explored with a focus on how participants' views concerning the high-risk behaviour of injecting drug use might influence their attitudes towards PLWHA. Results The analysis shows that active efforts were made by participants to separate their views of patients living with HIV/AIDS from injecting drug users. While the former were depicted as patients worthy of social support and inclusion, the latter were excluded on the basis that they were perceived as irresponsible 'social cheaters' who pose severe social and economic harm to the community. Absent in the narratives were references to wider socio-political and epidemiological factors related to drug use and needle sharing that expose injecting drug users to risk; these behaviours were constructed as individual choices, allowing HIV positive drug users to be blamed for their seropositive status. These attitudes could potentially have indirect negative implications on the nurses' opinions of patients living with HIV/AIDS more generally. Conclusion Decreasing the stigma associated with illicit drugs might play crucial role in improving attitudes towards patients living with HIV/AIDS. Providing health workers with a broader understanding of risk behaviours and redirecting government injecting drug policy to harm reduction are discussed as some of the ways for stigma intervention to move forward. PMID:18721474

  6. Drugs of Abuse.

    ERIC Educational Resources Information Center

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  7. Incident Type Drug Violation

    E-print Network

    Stowell, Michael

    Incident Type Theft Drug Violation Drug Violation Alcohol Violation Drug Violation Alcohol/07/2015 01:08 1855 ATHENS ST Boulder CO 80302 UNLAWFUL POSSESSION OR SALE OF MJ BY Referred Date/Time Occured:25 2015-00002429 11/06/2015 23:41 2250 WILLARD LOOP DR Boulder CO 80309 UNLAWFUL POSSESSION OR SALE OF MJ

  8. Incident Type Drug Violation

    E-print Network

    Stowell, Michael

    Incident Type Theft Drug Violation Drug Violation Drug Violation Criminal Trespass Criminal-00002237 10/22/2015 00:38 600 30TH ST Boulder CO 80310 UNLAWFUL POSSESSION OR SALE OF MJ BY Cleared - Summons:38 - 10/22/2015 01:13 2015-00002237 10/22/2015 00:38 600 30TH ST Boulder CO 80310 ILLEGAL POSSESSION

  9. Incident Type Drug Violation

    E-print Network

    Stowell, Michael

    Incident Type Drug Violation Drug Violation Drug Violation Disturbance Fraud/Forgery Criminal 80303 UNLAWFUL POSSESSION OR SALE OF MJ BY Cleared - Summons Date/Time Occured 11/10/2015 00:19 - 11/10/2015 00:19 3300 BASELINE RD Boulder CO 80303 ILLEGAL POSSESSION OF MARIJUANA Cleared - Summons Case Number

  10. Signs of Drug Use

    MedlinePLUS

    ... Facts and Fiction What You Should Know About Marijuana Concentrates/ Honey Butane Oil Consequences How Drugs Alter Brain Development and Affect Teens How Drugs Alter Brain Development and Affect Teens The Negative Health Effects of Marijuana Use State and Federal Drug Laws Treatment and ...

  11. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  12. Investigational Drug Steering Committee

    Cancer.gov

    The Investigational Drug Steering Committee collaborates with the NCI in the design and prioritization of early phase drug development trials conducted by the Experimental Therapeutics Clinical Trials Network (ETCTN) with agents for which NCI’s Cancer Therapy and Evaluation Program (CTEP) holds an Investigational New Drug (IND) application.

  13. [Fluoroquinolones. Drug interactions].

    PubMed

    Rusu, G; D?nil?, G

    2000-01-01

    This review summarizes clinically relevant drug-drug interactions for fluoroquinolones: antiacids containing aluminum and magnesium salts, iron or zinc preparations, sucralfate, cimetidine, ranitidine, warfarina, cyclosporin, rifampin, oral contraceptive steroids, benzodiazepine, probenecid, beta-lactam antibiotics, nonsteroidal anti-inflammatory drugs, metronidazole, theophylline, caffeine. PMID:12089990

  14. Benign positional vertigo - aftercare

    MedlinePLUS

    Vertigo - positional - aftercare; Benign paroxysmal positional vertigo - aftercare; BPPV - aftercare ... Your doctor may have treated your vertigo with the Epley maneuver. ... ear problem that causes BPPV. It usually works quickly. For ...

  15. Positional Plagiocephaly (Flattened Head)

    MedlinePLUS

    ... happens when a baby sleeps in the same position most of the time or because of problems ... surgery. Simple practices like changing a baby's sleep position, holding your baby, and providing lots of "tummy ...

  16. Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions

    MedlinePLUS

    ... Home Current Issue Past Issues Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions Past Issues / ... Drug Abuse during their first Drug Facts Chat Day. Photo courtesy of NIDA The questions poured in… ...

  17. Presumptive Treatment of Malaria from Formal and Informal Drug Vendors in Nigeria

    PubMed Central

    Isiguzo, Chinwoke; Anyanti, Jennifer; Ujuju, Chinazo; Nwokolo, Ernest; De La Cruz, Anna; Schatzkin, Eric; Modrek, Sepideh; Montagu, Dominic; Liu, Jenny

    2014-01-01

    Background Despite policies that recommend parasitological testing before treatment for malaria, presumptive treatment remains widespread in Nigeria. The majority of Nigerians obtain antimalarial drugs from two types of for-profit drug vendors—formal and informal medicine shops—but little is known about the quality of malaria care services provided at these shops. Aims This study seeks to (1) describe the profile of patients who seek treatment at different types of drug outlets, (2) document the types of drugs purchased for treating malaria, (3) assess which patients are purchasing recommended drugs, and (4) estimate the extent of malaria over-treatment. Methods In urban, peri-urban, and rural areas in Oyo State, customers exiting proprietary and patent medicine vendor (PPMV) shops or pharmacies having purchased anti-malarial drugs were surveyed and tested with malaria rapid diagnostic test. A follow-up phone survey was conducted four days after to assess self-reported drug administration. Bivariate and multivariate regression analysis was conducted to determine the correlates of patronizing a PPMV versus pharmacy, and the likelihood of purchasing an artemisinin-combination therapy (ACT) drug. Results Of the 457participants who sought malaria treatment in 49 enrolled outlets, nearly 92% had diagnosed their condition by themselves, a family member, or a friend. Nearly 60% pharmacy customers purchased an ACT compared to only 29% of PPMV customers, and pharmacy customers paid significantly more on average. Multivariate regression results show that patrons of PPMVs were younger, less wealthy, waited fewer days before seeking care, and were less likely to be diagnosed at a hospital, clinic, or laboratory. Only 3.9% of participants tested positive with a malaria rapid diagnostic test. Conclusions Poorer individuals seeking care at PPMVs are more likely to receive inappropriate malaria treatment when compared to those who go to pharmacies. Increasing accessibility to reliable diagnosis should be explored to reduce malaria over-treatment. PMID:25333909

  18. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease

    PubMed Central

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raúl J

    2014-01-01

    The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease PMID:24799984

  19. Youth Sport Programs: An Avenue to Foster Positive Youth Development

    ERIC Educational Resources Information Center

    Fraser-Thomas, Jessica L.; Cote, Jean; Deakin, Janice

    2005-01-01

    Concern about the growth in adolescent problem behaviours (e.g. delinquency, drug use) has led to increased interest in positive youth development, and a surge in funding for "after school programs." We evaluate the potential of youth sport programs to foster positive development, while decreasing the risk of problem behaviours. Literature on the…

  20. Positive Psychology: Transforming Young Lives

    ERIC Educational Resources Information Center

    Brendtro, Larry K.; Mitchell, Martin L.

    2011-01-01

    To reach responsible independence, young people must become invested in setting their life course. A rich history of research and practice shows that democratic group climates foster autonomy and prosocial behavior. This article explores principles and practices for creating positive peer cultures to develop strengths and help youth meet their…