Sample records for drug shows positive

  1. New Drug Shows Promise Against Psoriasis

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_153105.html New Drug Shows Promise Against Psoriasis Ixekizumab appeared to ... the disease clearing up, but people on the new drug also reporting a marked improvement in their ...

  2. New Drug Shows Promise for MS

    MedlinePLUS

    ... drug appears to repair nerve damage seen in multiple sclerosis (MS) patients, results of an early trial suggest. ... those with optic neuritis go on to develop multiple sclerosis. Patients who received the experimental antibody had greater ...

  3. Family Checkup: Positive Parenting Prevents Drug Abuse

    MedlinePLUS

    ... Email Facebook Twitter Family Checkup: Positive Parenting Prevents Drug Abuse Could your kids be at risk for substance ... drugs. Research supported by the National Institute on Drug Abuse (NIDA) has shown the important role that parents ...

  4. Clinical False-Positive Drug Test Results

    Microsoft Academic Search

    Tai C. Kwong

    A confirmed positive drug test reassures all the parties involved in the drug testing process that the reported positive result\\u000a is an analytical true positive and as such is evidence that the individual has been exposed to the drug. That individual may\\u000a not be a drug abuser and may have a valid alternative explanation for the positive result. In this

  5. 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...

  6. 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

  7. 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

  8. Drugs Show Promise for Some Advanced Lung Cancers

    MedlinePLUS

    Drugs Show Promise for Some Advanced Lung Cancers Two experimental medications target mutation that fuels treatment resistance To use the sharing features on this page, please enable JavaScript. (*this news ...

  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. 1. OBLIQUE VIEW, NORTH AND EAST SIDES. VIEW SHOWS POSITION ...

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

    1. OBLIQUE VIEW, NORTH AND EAST SIDES. VIEW SHOWS POSITION OF BUILDING UNDER LEG OF TOWER 33. - Chollas Heights Naval Radio Transmitting Facility, PERS Support Storage Building, 6410 Zero Road, San Diego, San Diego County, CA

  12. 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

  13. 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

  14. Drug Shows Early Promise for Advanced Lung Cancer

    MedlinePLUS

    ... group of drugs that block a "pathway" called PD-1, which then frees up the immune system to ... a month. Last month, the FDA approved another PD-1 drug -- nivolumab (Opdivo) -- for treating some cases of ...

  15. 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

  16. MEK: A Single Drug Target Shows Promise in Multiple Cancers

    Cancer.gov

    Drugs that block the MEK protein have shown promise in several cancers. Trametinib has had encouraging results in patients with advanced melanoma, and selumetinib has been tested in patients with advanced thyroid and ovarian cancers.

  17. 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...

  18. New cancer drug shows promise for treating advanced melanoma

    Cancer.gov

    Researchers from UCLA's Jonsson Comprehensive Cancer Center report that a new drug in preliminary tests has shown promising results with very manageable side effects for treating patients with melanoma, the deadliest form of skin cancer. The results were presented at the 2013 meeting of the American Society of Clinical Oncology today in Chicago by Dr. Antoni Ribas, professor of medicine in the UCLA division of hematology-oncology, who led the research. Following Ribas’ presentation, the study was published online ahead of press in the New England Journal of Medicine.

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

    MedlinePLUS

    ... Drug Delivery System Shows Early Promise for Treating Lupus in Mice A drug delivery system using nanoparticle ... cells can potentially improve treatment approaches for systemic lupus erythematosus (SLE), according to research partially funded by ...

  20. Urine levels of drugs for which Triage DOA screening was positive.

    PubMed

    Moriya, Fumio

    2009-04-01

    The purpose of this study was to investigate the relationship between urine levels of target drugs of abuse for which Triage DOA gave positive results, as well as the cut-off levels for these drugs. Thirty-eight forensic urine samples positive for commonly abused drugs were involved. Of these samples, 12 were positive for barbiturates (BAR), 11 for benzodiazepines (BZO), 8 for opiates (OPI), 7 for amphetamines (AMP), and 4 for tricyclic antidepressants (TCA). In the BAR-positive urine samples, phenobarbital, amobarbital or barbital was detected at concentrations higher than cut-off levels. In the BZO-positive samples, diazepam, nordiazepam, triazolam, nitrazepam and/or midazolam was detected at concentrations lower than cut-off levels; in the triazolam-involved urine, alpha-hydroxytriazolam, a metabolite of triazolam, showed concentrations higher than cut-off level. In the AMP-positive samples, methamphetamine was detected at concentrations higher than cut-off level. Urine samples positive for OPI contained total dihydrocodeine, codeine or morphine at concentrations higher than cut-off levels. In TCA-positive samples, amitriptyline was detected at concentrations higher or lower than cut-off level, and clomipramine was detected at a concentration much lower than cut-off level. Metabolites of BZO and TCA, which are not typically analyzed by instrumental procedures, may cross-react to varying degrees with the antibodies used for Triage DOA. PMID:19261513

  1. Nanostructural systems developed with positive charge generation to drug delivery.

    PubMed

    An, Fei-Fei; Cao, Weipeng; Liang, Xing-Jie

    2014-08-01

    The surface charge of a nanostructure plays a critical role in modulating blood circulation time, nanostructure-cell interaction, and intracellular events. It is unfavorable to have positive charges on the nanostructure surface before arriving at the disease site because positively charged nanostructures interact strongly with blood components, resulting in rapid clearance from the blood, and suboptimal targeted accumulation at the tumor site. Once at the tumor site, however, the positive charge on the nanostructure surface accelerates uptake by tumor cells and promotes the release of payloads from the lysosomes to the cytosol or nucleus inside cells. Thus, the ideal nanocarrier systems for drug delivery would maintain a neutral or negatively charged surface during blood circulation but would then generate a positive surface charge after accumulation at the tumor site or inside the cancer cells. This Progress Report focuses on the design and application of various neutral or negatively charged nanostructures that can generate a positive charge in response to the tumor microenvironment or an external stimulus. PMID:24550201

  2. Drugs developed for treatment of diabetes show protective effects in Alzheimer's and Parkinson's diseases.

    PubMed

    Hölscher, Christian

    2014-10-25

    Type 2 diabetes has been identified as a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). In the brains of patients with AD and PD, insulin signaling is impaired. This finding has motivated new research that showed good effects using drugs that initially had been developed to treat diabetes. Preclinical studies showed good neuroprotective effects applying insulin or long lasting analogues of incretin peptides. In transgenic animal models of AD or PD, analogues of the incretin GLP-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality and reduced the symptoms of the diseases. Amyloid plaque load and synaptic loss as well as cognitive impairment had been prevented in transgenic AD mouse models, and dopaminergic loss of transmission and motor function has been reversed in animal models of PD. On the basis of these promising findings, several clinical trials are being conducted with the first encouraging clinical results already published. In several pilot studies in AD patients, the nasal application of insulin showed encouraging effects on cognition and biomarkers. A pilot study in PD patients testing a GLP-1 receptor agonist that is currently on the market as a treatment for type 2 diabetes (exendin-4, Byetta) also showed encouraging effects. Several other clinical trials are currently ongoing in AD patients, testing another GLP-1 analogue that is on the market (liraglutide, Victoza). Recently, a third GLP-1 receptor agonist has been brought to the market in Europe (Lixisenatide, Lyxumia), which also shows very promising neuroprotective effects. This review will summarise the range of these protective effects that those drugs have demonstrated. GLP-1 analogues show promise in providing novel treatments that may be protective or even regenerative in AD and PD, something that no current drug does. PMID:25331995

  3. Use of Vouchers to Reinforce Abstinence and Positive Behaviors among Clients in a Drug Court Treatment Program

    PubMed Central

    Prendergast, Michael L.; Hall, Elizabeth A.; Roll, John; Warda, Umme

    2008-01-01

    In response to growing numbers of drug offenders cycling in and out of the criminal justice system without treatment for underlying drug problems, the judicial system has increasingly adopted drug courts as a strategy to divert these offenders from incarceration to supervised drug treatment. Our aim was to determine if drug court treatment effectiveness could be improved using contingency management, in the form of twice-weekly vouchers, to reinforce abstinence and positive behaviors for 163 clients over 26 weeks. We found no significant differences in outcomes among the study groups, although the Treatment Plan Group that received reinforcement for positive behaviors showed a trend toward poorer performance. We suspect that the influence of the judge within the courtroom had a stronger impact on drug court clients’ attitudes, drug use behaviors and other outcomes than the relatively low-value vouchers awarded as part of the treatment protocol. PMID:17997267

  4. 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

  5. Nutritional status assessment of HIV-positive drug addicts.

    PubMed

    Varela, P; Marcos, A; Ripoll, S; Requejo, A; Herrera, P; Casas, A

    1990-05-01

    Since human immunodeficiency virus (HIV) is known to lead to modifications of immune function and interrelationships among malnutrition, anergy and drug addiction have been shown, the aim of this work was to assess the nutritional status of 36 male heroin addicts under a period of detoxication (3 months). They were divided into two groups: (1) HIV negative (n = 20) and (2) HIV positive (n = 16); heights, weights and serum albumin concentration were measured and immune function was tested, using delayed hypersensitivity skin tests containing 7 antigens. No significant differences in anthropometric measurements were found between both groups, but anthropometric improvement was shown in every patient after the detoxication period. Serum albumin, often used as a classical index of malnutrition, remained within the normal values in both groups. The whole response to skin tests was depressed in both groups and no significant differences were shown between them. Therefore, these results might suggest that in spite of the apparent anthropometric recovery and the normal values of albumin, a subclinical malnutrition was indicated by the depressed immune function, which was more noticeable in the HIV-positive group. PMID:2387276

  6. The T2 Mycobacterium tuberculosis genotype, predominant in Kampala, Uganda, shows negative correlation with antituberculosis drug resistance.

    PubMed

    Lukoye, Deus; Katabazi, Fred A; Musisi, Kenneth; Kateete, David P; Asiimwe, Benon B; Okee, Moses; Joloba, Moses L; Cobelens, Frank G J

    2014-07-01

    Surveillance of the circulating Mycobacterium tuberculosis complex (MTC) strains in a given locality is important for understanding tuberculosis (TB) epidemiology. We performed molecular epidemiological studies on sputum smear-positive isolates that were collected for anti-TB drug resistance surveillance to establish the variability of MTC lineages with anti-TB drug resistance and HIV infection. Spoligotyping was performed to determine MTC phylogenetic lineages. We compared patients' MTC lineages with drug susceptibility testing (DST) patterns and HIV serostatus. Out of the 533 isolates, 497 (93.2%) had complete DST, PCR, and spoligotyping results while 484 (90.1%) participants had results for HIV testing. Overall, the frequency of any resistance was 75/497 (15.1%), highest among the LAM (34.4%; 95% confidence interval [CI], 18.5 to 53.2) and lowest among the T2 (11.5%; 95% CI, 7.6 to 16.3) family members. By multivariate analysis, LAM (adjusted odds ratio [OR(adj)], 5.0; 95% CI, 2.0 to 11.9; P < 0.001) and CAS (OR(adj), 2.9; 95% CI, 1.4.0 to 6.3; P = 0.006) families were more likely to show any resistance than was T2. All other MTC lineages combined were more likely to be resistant to any of the anti-TB drugs than were the T2 strains (OR(adj), 1.7; 95% CI, 1.0 to 2.9; P = 0.040). There were no significant associations between multidrug resistance and MTC lineages, but numbers of multidrug-resistant TB strains were small. No association was established between MTC lineages and HIV status. In conclusion, the T2 MTC lineage negatively correlates with anti-TB drug resistance, which might partly explain the reported low levels of anti-TB drug resistance in Kampala, Uganda. Patients' HIV status plays no role with respect to the MTC lineage distribution. PMID:24777100

  7. The T2 Mycobacterium tuberculosis Genotype, Predominant in Kampala, Uganda, Shows Negative Correlation with Antituberculosis Drug Resistance

    PubMed Central

    Lukoye, Deus; Katabazi, Fred A.; Musisi, Kenneth; Kateete, David P.; Asiimwe, Benon B.; Okee, Moses; Joloba, Moses L.

    2014-01-01

    Surveillance of the circulating Mycobacterium tuberculosis complex (MTC) strains in a given locality is important for understanding tuberculosis (TB) epidemiology. We performed molecular epidemiological studies on sputum smear-positive isolates that were collected for anti-TB drug resistance surveillance to establish the variability of MTC lineages with anti-TB drug resistance and HIV infection. Spoligotyping was performed to determine MTC phylogenetic lineages. We compared patients' MTC lineages with drug susceptibility testing (DST) patterns and HIV serostatus. Out of the 533 isolates, 497 (93.2%) had complete DST, PCR, and spoligotyping results while 484 (90.1%) participants had results for HIV testing. Overall, the frequency of any resistance was 75/497 (15.1%), highest among the LAM (34.4%; 95% confidence interval [CI], 18.5 to 53.2) and lowest among the T2 (11.5%; 95% CI, 7.6 to 16.3) family members. By multivariate analysis, LAM (adjusted odds ratio [ORadj], 5.0; 95% CI, 2.0 to 11.9; P < 0.001) and CAS (ORadj, 2.9; 95% CI, 1.4.0 to 6.3; P = 0.006) families were more likely to show any resistance than was T2. All other MTC lineages combined were more likely to be resistant to any of the anti-TB drugs than were the T2 strains (ORadj, 1.7; 95% CI, 1.0 to 2.9; P = 0.040). There were no significant associations between multidrug resistance and MTC lineages, but numbers of multidrug-resistant TB strains were small. No association was established between MTC lineages and HIV status. In conclusion, the T2 MTC lineage negatively correlates with anti-TB drug resistance, which might partly explain the reported low levels of anti-TB drug resistance in Kampala, Uganda. Patients' HIV status plays no role with respect to the MTC lineage distribution. PMID:24777100

  8. Drugs For Male Sexual Dysfunction Show Promise In The Lab For Treating Female Sexual Disorders

    NSDL National Science Digital Library

    APS Communications Office (American Physiological Society Communications Office)

    2006-04-17

    This is an APS press release on a study that found that female sexual dysfunction may be, in part, the result of inadequate supply of blood to the female genitals and may be addressed with erectile dysfunction drugs. Originally developed as therapy for hypertension, these drugs work by dilating blood vessels sufficiently to produce erections in males. These drugs have not been fully explored in females.

  9. FOXP2 targets show evidence of positive selection in European populations.

    PubMed

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

    2013-05-01

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. PMID:23602712

  10. Student/Research assistant position: Detection of potential drug targets in

    E-print Network

    Rostock, Universität

    Student/Research assistant position: Detection of potential drug targets in cancer signaling for drug discovery in metabolic diseases (OPDD, Vera et al. 2007) to investigate new drug targets in cell signaling pathways involved in cancer progression. Precisely the student must deal with the following tasks

  11. Strut Position, Blood Flow, and Drug Deposition Implications for Single and Overlapping Drug-Eluting Stents

    Microsoft Academic Search

    Brinda Balakrishnan; Abraham R. Tzafriri; Philip Seifert; Adam Groothuis; Campbell Rogers; Elazer R. Edelman

    2010-01-01

    Background—The intricacies of stent design, local pharmacology, tissue biology, and rheology preclude an intuitive understanding of drug distribution and deposition from drug-eluting stents (DES). Methods and Results—A coupled computational fluid dynamics and mass transfer model was applied to predict drug deposition for single and overlapping DES. Drug deposition appeared not only beneath regions of arterial contact with the strut but

  12. 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

  13. Drug used in NIH-supported trial 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, multicenter trial, led by investigators from the Children's Oncology Group (COG), and supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

  14. Physical activity in a cohort of HIV-positive and HIV-negative injection drug users

    Microsoft Academic Search

    E. Smit; C. J. Crespo; R. D. Semba; D. Jaworowicz; D. Vlahov; E. P. Ricketts; F. A. Ramirez-Marrero; A. M. Tang

    2006-01-01

    Physical activity is beneficial for persons with HIV infection but little is known about the relationships between physical activity, HIV treatment and injection drug use (IDU). This study compared physical activity levels between HIV-negative and HIV-positive injection drug users (IDUs) and between HIV-positive participants not on any treatment and participants on highly active antiretroviral therapy (HAART). Anthropometric measurements were obtained

  15. Near Completely Humanized Liver in Mice Shows Human-Type Metabolic Responses to Drugs

    PubMed Central

    Tateno, Chise; Yoshizane, Yasumi; Saito, Naomi; Kataoka, Miho; Utoh, Rie; Yamasaki, Chihiro; Tachibana, Asato; Soeno, Yoshinori; Asahina, Kinji; Hino, Hiroshi; Asahara, Toshimasa; Yokoi, Tsuyoshi; Furukawa, Toshinori; Yoshizato, Katsutoshi

    2004-01-01

    Human hepatocytes were transplanted into urokinase-type plasminogen activator-transgenic SCID mice (uPA/SCID mice), which are immunodeficient and undergo liver failure. The transplanted cells were characterized in terms of their in vivo growth potential and functions. The human hepatocytes progressively repopulated the murine host liver. However, the recipients died when the replacement index (RI) of the human hepatocytes exceeded 50%. The hosts (chimeric mice) survived at RI >50% when treated with a drug that has anti-human complement factor activity, and these mice developed livers with RI values as high as 96%. In total, 36 chimeric mice were generated, and the rate of successful engraftment was as high as 92%. The yield of chimeric mice with RI >70% was 32%. The human hepatocytes in the murine host liver expressed mRNAs for a variety of human cytochrome P450 (hCYP) subtypes, in a manner that was similar to the donor liver. The mRNAs for hCYP3A4 and hCYP1A1/2 were induced in the liver in a CYP type-specific manner when the mice were treated with rifampicin and 3-methylcholanthrene, respectively. These results indicate that human hepatocytes that propagate in mice retain their normal pharmacological responses. We conclude that the chimeric mouse developed in the present study is a useful model for assessing the functions and pharmacological responses of human hepatocytes. PMID:15331414

  16. AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo.

    PubMed Central

    McKeown, S. R.; Hejmadi, M. V.; McIntyre, I. A.; McAleer, J. J.; Patterson, L. H.

    1995-01-01

    AQ4N (1,4-bis([2-(dimethylamino-N-oxide)ethyl]amino)5,8-dihydroxy- anthracene-9,10-dione) is a novel alkylaminoanthraquinone N-oxide which, on reduction, forms a stable DNA affinic cytotoxic compound AQ4. The in vivo anti-tumour efficacy of AQ4N was investigated in B6D2F1 mice bearing the T50/80 mammary carcinoma. The effect of the drug was evaluated in combination with hypobaric hypoxia and with radiation (single and multiple fractions). Systemic toxicity was assessed by weight loss post treatment. This was low for AQ4N and was less than that obtained with the bioreductive drugs, RSU 1069 (1-[3-aziridinyl-2-hydroxypropyl]-2-nitroimidazole) and SR 4233 (Tirapazamine, 3-amino-1,2,4-benzotriazine-1,4-dioxide). The anti-tumour effect of AQ4N was potentiated in vivo by combination with hypobaric hypoxia with a dose enhancement ratio of 5.1. This is consistent with the proposal that AQ4N was reduced in vivo to AQ4, resulting in enhanced anti-tumour toxicity. When AQ4N (200 mg kg-1) was combined with single dose radiation (12 Gy) the drug was shown to have an additive interaction with radiation. This was obtained even if the drug was administered from 4 days before to 6 h after radiation treatment. Equivalent anti-tumour activity was also shown when both AQ4N (200 mg kg-1) and radiation (5 x 3 Gy) were administered in fractionated schedules. In conclusion, AQ4N shows significant potential as a bioreductive drug for combination with fractionated radiotherapy. PMID:7599069

  17. Gene expression analysis of two extensively drug-resistant tuberculosis isolates show that two-component response systems enhance drug resistance.

    PubMed

    Yu, Guohua; Cui, Zhenling; Sun, Xian; Peng, Jinfu; Jiang, Jun; Wu, Wei; Huang, Wenhua; Chu, Kaili; Zhang, Lu; Ge, Baoxue; Li, Yao

    2015-05-01

    Global analysis of expression profiles using DNA microarrays was performed between a reference strain H37Rv and two clinical extensively drug-resistant isolates in response to three anti-tuberculosis drug exposures (isoniazid, capreomycin, and rifampicin). A deep analysis was then conducted using a combination of genome sequences of the resistant isolates, resistance information, and related public microarray data. Certain known resistance-associated gene sets were significantly overrepresented in upregulated genes in the resistant isolates relative to that observed in H37Rv, which suggested a link between resistance and expression levels of particular genes. In addition, isoniazid and capreomycin response genes, but not rifampicin, either obtained from published works or our data, were highly consistent with the differentially expressed genes of resistant isolates compared to those of H37Rv, indicating a strong association between drug resistance of the isolates and genes differentially regulated by isoniazid and capreomycin exposures. Based on these results, 92 genes of the studied isolates were identified as candidate resistance genes, 10 of which are known resistance-related genes. Regulatory network analysis of candidate resistance genes using published networks and literature mining showed that three two-component regulatory systems and regulator CRP play significant roles in the resistance of the isolates by mediating the production of essential envelope components. Finally, drug sensitivity testing indicated strong correlations between expression levels of these regulatory genes and sensitivity to multiple anti-tuberculosis drugs in Mycobacterium tuberculosis. These findings may provide novel insights into the mechanism underlying the emergence and development of drug resistance in resistant tuberculosis isolates and useful clues for further studies on this issue. PMID:25869645

  18. Impact of a positive hepatitis C diagnosis on homeless injecting drug users: a qualitative study

    PubMed Central

    Tompkins, Charlotte NE; Wright, Nat MJ; Jones, Lesley

    2005-01-01

    Background Increasing numbers of injecting drug users are presenting to primary care and a growing number of general practices are specifically providing care for homeless people. Injecting drug users are at the greatest risk of hepatitis C infection and homeless drug misusers, because of their drug-taking behaviour and patterns, have been identified as being at greater risk of harm of blood-borne diseases than the general population. However, little work has been conducted with injecting drug users or homeless people who have hepatitis C and little is known about how the virus may affect them. Aim To explore the impact of a positive hepatitis C diagnosis on homeless injecting drug users. Design of study This study employed qualitative research. In-depth interviews allowed the exploration of the impact of a potentially life-threatening diagnosis within the context of a person's expressed hierarchy of needs. Setting A primary care centre for homeless people in the north of England. Method In-depth interviews about the impact of a positive hepatitis C diagnosis on their lives were conducted with 17 homeless injecting drug users who had received a positive hepatitis C diagnosis. The interviews were audiotaped, transcribed, and analysed using the framework approach. Results Receiving a positive diagnosis for hepatitis C resulted in feelings of shock, devastation, disbelief, anger, and questioning. A positive diagnosis had lasting social, emotional, psychological, behavioural, and physical effects on homeless injecting drug users, even years after the initial diagnosis. Most responders were diagnosed by a doctor in primary care or by hospital staff; however, not all had sought testing and a number were tested while inpatients and were unaware that blood had been taken for hepatitis C virus serology. Conclusions The implications for clinical policy and primary care practice are discussed, including the issues of patient choice, confidentiality, and pre- and post-test discussions. Post-test discussions should be followed up with additional social, psychological, and medical support and counselling. PMID:15826432

  19. New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases

    PubMed Central

    Hölscher, Christian

    2014-01-01

    Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable. PMID:25558231

  20. Dysphoric students show higher use of the observer perspective in their retrieval of positive versus negative autobiographical memories.

    PubMed

    Nelis, Sabine; Debeer, Elise; Holmes, Emily A; Raes, Filip

    2013-01-01

    Autobiographical memories are retrieved as images from either a field perspective or an observer perspective. The observer perspective is thought to dull emotion. Positive affect is blunted in depressed mood. Consequently, are positive events recalled from an observer perspective in depressed mood? We investigated the relationship between memory vantage perspective and depressive symptoms in a student sample. Participants completed the Autobiographical Memory Test (AMT; Williams & Broadbent, 1986) and assessed the perspective accompanying each memory. The Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) and the Responses to Positive Affect questionnaire (RPA; Feldman, Joormann, & Johnson, 2008) were administered. The results showed a small positive association between depressive symptoms and the use of an observer perspective for positive autobiographical memories, but not for negative memories. Furthermore, comparing a subgroup with clinically significant symptom levels (dysphoric students) with non-dysphoric individuals revealed that dysphoric students used an observer perspective more for positive memories compared with negative memories. This was not the case for non-dysphoric students. The observer perspective in dysphorics was associated with a dampening cognitive style in response to positive experiences. PMID:23083015

  1. Positive predictive values of abused drug immunoassays on the Beckman Synchron in a veteran population.

    PubMed

    Dietzen, D J; Ecos, K; Friedman, D; Beason, S

    2001-04-01

    The pressure to reduce the cost of analytic testing makes it tempting to discontinue routine confirmation of urine specimens positive for drugs of abuse by immunoassay. Beyond the economic motivation, the requirement for confirmation should be driven by the positive predictive value of the screening tests. We have quantitated positive predictive values of our screening immunoassays in a large metropolitan Veterans Affairs Medical Center. We reviewed the confirmatory rate of urine specimens positive for drugs of abuse with Beckman Synchron reagents from June 1998 to June 1999 and tabulated the false-positive screening rate. There were 175 instances of false-positive screens during the 13 months we analyzed. Positive predictive values ranged from 0% (amphetamine) to 100% (THC). We determined that the low positive predictive value of the amphetamine assay in our laboratory was primarily due to the use of ranitidine (Zantac). Urine specimens containing greater than 43 microg/mL ranitidine were positive in our amphetamine assay. This concentration is routinely exceeded in our patients taking ranitidine. In our clinical and analytic setting, the Beckman THC assay did not require confirmation. The positive predictive values of the Beckman opiate, cocaine, barbiturate, propoxyphene, and methadone immunoassays dictate routine confirmatory testing in specimens that screen positive for these substances. Finally, because of its extreme sensitivity to ranitidine, the Beckman amphetamine assay has little utility in our laboratory setting. PMID:11327349

  2. Regions with higher Medicare Part D spending show better drug adherence, but not lower medicare costs for two diseases.

    PubMed

    Stuart, Bruce; Shoemaker, J Samantha; Dai, Mingliang; Davidoff, Amy J

    2013-01-01

    A quarter-century of research on geographic variation in Medicare costs has failed to find any positive association between high spending and better health outcomes. We conducted this study using a 5 percent random sample of Medicare beneficiaries with diabetes or heart failure in 2006 and 2007 to see whether there was any correlation between geographic variation in Part D spending and good medication-taking behavior-and, if so, whether that correlation resulted in reduced Medicare Parts A and B spending on diabetes and heart failure treatments. We found that beneficiaries residing in areas characterized by higher adjusted drug spending had significantly more "therapy days"-days with recommended medications on hand-than did beneficiaries in lower-spending areas. However, we did not find that this factor translated into short-term savings in Medicare treatment costs for these two diseases. This result might not be surprising, since returns from medication adherence can take years to manifest. At the same time, discovering which regional factors are responsible for differences in drug spending and medication practices should be a high priority. If the observed differences are related to poor physician communication or lack of good care coordination, then appropriately designed policy tools-including accountable care organizations, medical homes, and provider quality reporting initiatives-might help address them. PMID:23297279

  3. CD133-Positive Cells from Non-Small Cell Lung Cancer Show Distinct Sensitivity to Cisplatin and Afatinib.

    PubMed

    Alama, Angela; Gangemi, Rosaria; Ferrini, Silvano; Barisione, Gaia; Orengo, Anna Maria; Truini, Mauro; Bello, Maria Giovanna Dal; Grossi, Francesco

    2015-06-01

    The standard of care for advanced non-small cell lung cancer (NSCLC) consists in cisplatin-combination chemotherapy. In patients bearing tumors with activating mutations of the epidermal growth factor receptor (EGFR), the inhibition of the EGFR intracellular tyrosine kinase can induce up to 80 % response rates. However, both therapeutic strategies will eventually lead to recurrent disease due to the development of drug resistance. The identification of rare cancer stem-like cells able to repopulate the tumor, after failure to standard treatment modalities, has led to characterize these cells as potential therapeutic targets. This article will address the role of the CD133/EpCAM stem cell-related markers and explore cell sensitivity to cisplatin and to the EGFR-tyrosine kinase inhibitor, afatinib. Three human NSCLC cell lines, one wild-type (A549) and two harboring EGFR mutations (H1650 and H1975), as well as 20 NSCLC primary cultures, were grown in non-differentiating culture conditions for stem cell enrichment. Flow-cytometry analyses of CD133 and EpCAM and cell sensitivity to cisplatin and afatinib were performed. Moreover, the expression of activated EGFR was assessed by Western blot. The cell lines and primary cultures grown in non-differentiating culture conditions were enriched with CD133/EpCAM-positive cells and were significantly more resistant to cisplatin and more sensitive to afatinib as compared to the differentiated counterpart. In addition, increased EGFR-phosphorylation in non-differentiated cultures was observed. The present findings suggest that afatinib might be beneficial for patients bearing tumors with constitutively activated EGFR, to target chemo-resistant CD133/EpCAM-positive cancer stem cells. PMID:25678473

  4. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis.

    PubMed

    Farhat, Maha R; Shapiro, B Jesse; Kieser, Karen J; Sultana, Razvan; Jacobson, Karen R; Victor, Thomas C; Warren, Robin M; Streicher, Elizabeth M; Calver, Alistair; Sloutsky, Alex; Kaur, Devinder; Posey, Jamie E; Plikaytis, Bonnie; Oggioni, Marco R; Gardy, Jennifer L; Johnston, James C; Rodrigues, Mabel; Tang, Patrick K C; Kato-Maeda, Midori; Borowsky, Mark L; Muddukrishna, Bhavana; Kreiswirth, Barry N; Kurepina, Natalia; Galagan, James; Gagneux, Sebastien; Birren, Bruce; Rubin, Eric J; Lander, Eric S; Sabeti, Pardis C; Murray, Megan

    2013-10-01

    M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly sequenced and 7 previously sequenced M. tuberculosis whole genomes, we identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains. By searching for convergent evolution--the independent fixation of mutations in the same nucleotide position or gene--we recovered 100% of a set of known resistance markers. We also found evidence of positive selection in an additional 39 genomic regions in resistant isolates. These regions encode components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways. Mutations in these regions could directly confer resistance or compensate for fitness costs associated with resistance. Functional genetic analysis of mutations in one gene, ponA1, demonstrated an in vitro growth advantage in the presence of the drug rifampicin. PMID:23995135

  5. Etoricoxib-induced fixed drug eruption with positive lesional patch tests.

    PubMed

    Calistru, Ana Maria; Cunha, Ana Paula; Nogueira, Ana; Azevedo, Filomena

    2011-06-01

    Fixed drug eruption (FDE) is most commonly associated with antibiotics, anticonvulsants, and nonnarcotic analgens, including nonsteroidal anti-inflammatory drugs (NSAIDs). However, the newer cyclooxygenase 2 (COX-2) inhibitors have been rarely reported to cause FDE. We report the case of a 52-year-old Caucasian woman with erythematous pruritic plaques on the neck, left forearm, and second finger of the right hand, healing with hyperpigmentation and recurring in the same locations. The patient was sporadically taking oral etoricoxib 90 mg for her back pain and noticed the relation between administration of the drug and skin lesions, the time interval decreasing progressively from 1 week to 30 minutes. No other signs, symptoms, or drug intake was mentioned. The patch tests with etoricoxib 1% and 5% in petrolatum were positive at the location of the lesions and negative on the back (nonlesional skin). Standard European and NSAID series were negative. Patch tests of 10 healthy controls with etoricoxib 1% and 5% in petrolatum were negative. After the avoidance of the drug, no relapse was mentioned. The patch test was reliable for the diagnosis of FDE, avoiding the need for subsequent oral provocation testing and therefore preventing the possible adverse effects. Despite being regarded as a safe drug, the occurrence of cutaneous adverse reactions to etoricoxib should be considered, especially in the setting of its increasing use in pain control. PMID:21108578

  6. Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey

    ERIC Educational Resources Information Center

    Sznitman, Sharon R.; Dunlop, Sally M.; Nalkur, Priya; Khurana, Atika; Romer, Daniel

    2012-01-01

    Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools…

  7. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.

    PubMed

    Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; Zhang, Bin; Schmidhuber, Sabine; Yi, Sun-Ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

    2012-08-01

    Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. Using gene expression profiling, we found that the development of drug resistance was accompanied by massive transcriptional upregulation of genes that are associated with general inflammatory responses such as the metalloproteinase MMP9. MMP9 protein levels and enzymatic activity were also increased in ALL cells that had become nilotinib-tolerant. Activation of p38, Akt and Erk correlated with the development of environment-mediated drug resistance (EMDR), and inhibitors of Akt and Erk in combination with nilotinib reduced the ability of the cells to develop resistance. However, inhibition of p38 promoted increased resistance to nilotinib. We conclude that development of EMDR by ALL cells involves changes in numerous intracellular pathways. Development of tolerance to drugs such as nilotinib may therefore be circumvented by simultaneous treatment with other drugs having divergent targets. PMID:22934254

  8. Influence of lower body positive pressure on upper airway cross-sectional area in drug-resistant hypertension.

    PubMed

    Friedman, Oded; Bradley, T Douglas; Logan, Alexander G

    2013-01-01

    We previously showed that in hypertensive patients the amount of fluid displaced from the legs overnight is directly related to the severity of obstructive sleep apnea and that the rostral fluid shift was greater in drug-resistant hypertensive patients. The findings suggested that this fluid redistribution increases upper airway collapsibility, yet more direct evidence is lacking. The present study examines the effects of graded lower body positive pressure on leg fluid volume, upper airway cross-sectional area, and neck circumference in patients with drug-resistant hypertension (n=25) and controlled hypertension (n=15). In both groups, the reduction in mean upper airway cross-sectional area and oropharyngeal junction area, assessed by acoustic pharyngometry, and the increase in neck circumference, determined by mercury strain gauge plethysmography, were related to the amount of fluid displaced from the legs (R(2)=0.41, P<0.0001; R(2)=0.42, P<0.0001; and R(2)=0.47, P<0.0001, respectively). Displacement of leg fluid volume was significantly greater in patients with drug-resistant hypertension than in controlled hypertension (P<0.0001), and as a consequence, the former experienced greater reductions in mean upper airway cross-sectional area and oropharyngeal junction area (P=0.001 and P<0.0001, respectively). The findings support the concept that in hypertensive subjects, rostral fluid displacement may participate in the pathogenesis of obstructive sleep apnea by narrowing the upper airway and making it more susceptible to collapse during sleep. The exaggerated fluid volume displacement from the legs and upper airway response to lower body positive pressure in patients with drug-resistant hypertension provide additional evidence of an important link between drug-resistant hypertension and obstructive sleep apnea. PMID:23150515

  9. Evaluating the athlete's claim of an unintentional positive urine drug test.

    PubMed

    Anderson, Jeffrey M

    2011-07-01

    During a urine drug testing program, an athlete may make a claim that the results of a positive test have arisen from factors that were out of his or her control, and therefore, he or she should not be held responsible for the results. Some of these claims may include classic claims of passive inhalation of marijuana smoke or ingestion of poppy seeds leading to positive tests. In addition, with the proliferation of nutritional supplements on the market, many athletes claim that they accidentally ingested a banned substance contained in one of these. It is important that any sports medicine physician involved with sports drug testing be informed of the data that either support or refute these claims and that he or she contribute to a program wherein adequate education and policy establishment help to limit the likelihood of such claims. This article will review the data to help address these claims. PMID:23531893

  10. Safe Syringe Disposal is Related to Safe Syringe Access among HIV-positive Injection Drug Users

    Microsoft Academic Search

    Phillip O. Coffin; Mary H. Latka; Carl Latkin; Yingfeng Wu; David W. Purcell; Lisa Metsch; Cynthia Gomez; Marc N. Gourevitch

    2007-01-01

    We evaluated the effect of syringe acquisition on syringe disposal among HIV-positive injection drug users (IDUs) in Baltimore,\\u000a New York City, and San Francisco (N = 680; mean age 42 years, 62% male, 59% African-American, 21% Hispanic, 12% White). Independent predictors of safe disposal\\u000a were acquiring syringes through a safe source and ever visiting a syringe exchange program. Weaker predictors included living\\u000a in

  11. Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper.

    PubMed

    Bonadonna, P; Pagani, M; Aberer, W; Bilņ, M B; Brockow, K; Oude Elberink, H; Garvey, L; Mosbech, H; Romano, A; Zanotti, R; Torres, M J

    2015-07-01

    Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. PMID:25824492

  12. OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer.

    PubMed

    Sänger, Nicole; Ruckhäberle, Eugen; Bianchini, Giampaolo; Heinrich, Tomas; Milde-Langosch, Karin; Müller, Volkmar; Rody, Achim; Solomayer, Erich Franz; Fehm, Tanja; Holtrich, Uwe; Becker, Sven; Karn, Thomas

    2014-10-01

    The RANK/RANKL/OPG pathway is well known for bone destruction in skeletal metastases but has also been implicated in osteoclast-independent roles in tumorigenesis and de novo metastasis. Experimental data suggest contribution of progesterone to tumorigenesis may be mediated by RANKL. Importantly, modulation of this pathway became possible through the availability of denosumab, an artificial counterpart of OPG, but significant gaps remain in the translation of preclinical findings on the pathway. We analyzed gene expression of RANK, RANKL and OPG from 40 Affymetrix datasets encompassing 4467 primary breast cancers and focused on ER positive disease. We did not observe a significant prognostic value of RANK and RANKL mRNA expression. In contrast, OPG was associated with a better prognosis among 1941 ER positive cancers (HR 0.64, 95% CI 0.53-0.77; P < 0.0001) using a cutoff from its highly bimodal expression. We detected considerable heterogeneity regarding the prognostic value of OPG between different datasets. This heterogeneity could neither be attributed to technical reasons nor to differences in standard clinical parameters or treatments of the cohorts. Interestingly, the prognostic value of the progesterone receptor and of OPG showed similar cohort specific effects. Still both factors were no surrogates for each other but contributed independent prognostic value in multivariate analyses. Thus, both OPG and PgR are independently associated with good prognosis in ER positive breast cancer. However both markers share common cohort specific differences in contrast to proliferation markers as Ki67 which may be based on the underlying biology. PMID:24785095

  13. Social networks and HCV viremia among anti-HCV positive rural drug users

    PubMed Central

    YOUNG, A. M.; JONAS, A. B.; HAVENS, J. R.

    2012-01-01

    Summary Though social networks are known to play an important role in drug-using behaviors associated with HCV infection, literature on social networks and HCV is inconsistent. This exploratory study examined HCV RNA distribution within a social network of anti-HCV positive rural Appalachia nonmedical prescription opioid users (NMPOUs). Participants were tested serologically for HCV RNA, and behavioral, demographic, and network data were collecting using interview-administered questionnaires. Multivariate analyses were performed using logistic regression. Behavioral and demographic characteristics did not differ by RNA status. In the multivariate model, recent injection drug users were more likely to be RNA-positive (OR: 4.06, 95% CI: 1.04 – 15.83), and turnover into one’s drug network was significantly protective (OR: 0.15, 95% CI: 0.03-0.75). This is the first study to date to examine HCV distribution among rural NMPOUs from a network perspective and demonstrates that network characteristics significantly contribute to the epidemiology of HCV in this understudied, high-risk population. PMID:22717190

  14. FLT3 Inhibition and Mechanisms of Drug Resistance in mutant FLT3-Positive AML

    PubMed Central

    Weisberg, Ellen; Barrett, Rosemary; Liu, Qingsong; Stone, Richard; Gray, Nathanael; Griffin, James D.

    2015-01-01

    An appealing therapeutic target for AML is constitutively-activated, mutant FLT3, which is expressed in a subpopulation of AML patients and is generally a poor prognostic indicator in patients under the age of 65. There are currently several FLT3 inhibitors that are undergoing clinical investigation. However, the discovery of drug-resistant leukemic blast cells in FLT3 inhibitor-treated AML patients has prompted the search for novel, structurally diverse FLT3 inhibitors that could be alternatively used to circumvent drug resistance. Here, we provide an overview of FLT3 inhibitors under preclinical and clinical investigation, and we discuss mechanisms whereby AML cells develop resistance to FLT3 inhibitors, and the ways in which combination therapy could potentially be utilized to override drug resistance. We discuss how the cross-talk between major downstream signaling pathways, such as PI3K/PTEN/Akt/mTOR, RAS/Raf/MEK/ERK, and Jak/STAT, can be exploited for therapeutic purposes by targeting key signaling molecules with selective inhibitors, such as mTOR inhibitors, HSP90 inhibitors, or farnesyltransferase inhibitors, and identifying those agents with the ability to positively combine with inhibitors of FLT3, such as PKC412 and sunitinib. With the widespread onset of drug resistance associated with tyrosine kinase inhibitors, due to mechanisms involving development of point mutations or gene amplification of target proteins, the use of a multi-targeted therapeutic approach is of potential clinical benefit. PMID:19467916

  15. Functional analysis of a novel positive allosteric modulator of AMPA receptors derived from a structure-based drug design strategy.

    PubMed

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

    2013-01-01

    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. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PMID:22735771

  16. A polyphenylene dendrimer drug transporter with precisely positioned amphiphilic surface patches.

    PubMed

    Stangenberg, René; Wu, Yuzhou; Hedrich, Jana; Kurzbach, Dennis; Wehner, Daniel; Weidinger, Gilbert; Kuan, Seah Ling; Jansen, Malin Insa; Jelezko, Fedor; Luhmann, Heiko J; Hinderberger, Dariush; Weil, Tanja; Müllen, Klaus

    2015-02-18

    The design and synthesis of a polyphenylene dendrimer (PPD 3) with discrete binding sites for lipophilic guest molecules and characteristic surface patterns is presented. Its semi-rigidity in combination with a precise positioning of hydrophilic and hydrophobic groups at the periphery yields a refined architecture with lipophilic binding pockets that accommodate defined numbers of biologically relevant guest molecules such as fatty acids or the drug doxorubicin. The size, architecture, and surface textures allow to even penetrate brain endothelial cells that are a major component of the extremely tight blood-brain barrier. In addition, low to no toxicity is observed in in vivo studies using zebrafish embryos. The unique PPD scaffold allows the precise placement of functional groups in a given environment and offers a universal platform for designing drug transporters that closely mimic many features of proteins. PMID:25182694

  17. Fragmentation of toxicologically relevant drugs in positive-ion liquid chromatography-tandem mass spectrometry.

    PubMed

    Niessen, W M A

    2011-01-01

    The identification of drugs and related compounds by LC-MS-MS is an important analytical challenge in several application areas, including clinical and forensic toxicology, doping control analysis, and environmental analysis. Although target-compound based analytical strategies are most frequently applied, at some point the information content of the MS-MS spectra becomes relevant. In this article, the positive-ion MS-MS spectra of a wide variety of drugs and related substances are discussed. Starting point was an MS-MS mass spectral library of toxicologically relevant compounds, available on the internet. The positive-ion MS-MS spectra of ?570 compounds were interpreted by chemical and therapeutic class, thus involving a wide variety of drug compound classes, such benzodiazepines, beta-blockers, angiotensin-converting enzyme inhibitors, phenothiazines, dihydropyridine calcium channel blockers, diuretics, local anesthetics, vasodilators, as well as various subclasses of anti-diabetic, antidepressant, analgesic, and antihistaminic drugs. In addition, the scientific literature was searched for available MS-MS data of these compound classes and the interpretation thereof. The results of this elaborate study are presented in this article. For each individual compound class, the emphasis is on class-specific fragmentation, as discussing fragmentation of all individual compounds would take far too much space. The recognition of class-specific fragmentation may be quite informative in determining the compound class of a specific unknown, which may further help in the identification. In addition, knowledge on (class-specific) fragmentation may further help in the optimization of the selectivity in targeted analytical approaches of compounds of one particular class. PMID:21294151

  18. Individuals Family History Positive for Alcoholism Show fMRI Differences in Reward Sensitivity that are Related to Impulsivity Factors

    PubMed Central

    Andrews, Melissa M.; Meda, Shashwath A.; Thomas, Andre D.; Potenza, Marc N.; Krystal, John H; Worhunsky, Patrick; Stevens, Michael C.; O’Malley, Stephanie; Book, Gregory A.; Reynolds, Brady; Pearlson, Godfrey D.

    2013-01-01

    Background Substance abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay (MID) task. However there is limited information on whether this uncharacteristic behavior represents a biological predisposition towards alcohol abuse, a consequence of chronic alcohol use, or both. Methods We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a MID task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. Results During reward anticipation, fMRI data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Conclusions Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism FHP individuals in multiple regards. PMID:21126735

  19. Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey

    Microsoft Academic Search

    Sharon R. SznitmanSally; Sally M. Dunlop; Priya Nalkur; Atika Khurana; Daniel Romer

    Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance\\u000a use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This\\u000a study examined the association between school drug testing programs and student substance use in schools with different climates.\\u000a The analysis was based on

  20. Mechanisms of resistance to antimicrobial drugs in pathogenic Gram-positive cocci.

    PubMed

    Mlynarczyk, B; Mlynarczyk, A; Kmera-Muszynska, M; Majewski, S; Mlynarczyk, G

    2010-09-01

    Many species of Gram-positive cocci are pathogenic. The most important are staphylococci, streptococci, and enterococci. Widespread usage of antibiotics was the main cause for the appearance and spread of resistance to almost all antimicrobials. The occurrence, mechanisms, and genetic background of resistance to antimicrobial drugs other than beta-lactams and glycopeptides among pathogenic staphylococci, streptococci, and enterococci are discussed in the text. Well-established agents (such as macrolides, lincosamides, streptogramins, aminoglycosides, quinolones, mupirocin, chloramphenicol) as well as new agents (linezolid, daptomycin, quinupristine/dalfopristine, ratapamulin, tigecycline, iclaprim and new generations of quinolones) are considered. PMID:20370697

  1. Drug-Tolerant Cancer Cells Show Reduced Tumor-Initiating Capacity: Depletion of CD44+ Cells and Evidence for Epigenetic Mechanisms

    PubMed Central

    Qin, Jichao; Li, Hangwen; Liu, Can; Calhoun-Davis, Tammy; Coletta, Luis Della; Klostergaard, Jim; Fokt, Izabela; Skora, Stanislaw; Priebe, Waldemar; Bi, Yongyi; Tang, Dean G.

    2011-01-01

    Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44+ cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration, whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many “stemness” genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44+ tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms. PMID:21935404

  2. Observation of swelling process and diffusion front position during swelling in hydroxypropyl methyl cellulose (HPMC) matrices containing a soluble drug

    Microsoft Academic Search

    Paolo Colombo; Ruggero Bettini; Nikolaos A. Peppas

    1999-01-01

    The behavior of gel layer thickness in swellable hydroxypropyl methyl cellulose matrices loaded with increasing amounts of soluble and colored drug and exhibiting swelling, diffusion and erosion fronts, was studied using a colorimetric technique. The effect of the drug loading on the front position in the gel layer, in particular, on the presence of a diffusion front and its movement,

  3. 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

  4. 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, Glņria; Palomeras, Sņnia; Turrado, Carlos; Campuzano, Ņscar; Carrión-Salip, Dolors; Massaguer, Anna; Brugada, Ramon; Palafox, Marta; Gómez-Miragaya, Jorge; Gonzįlez-Suįrez, 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

  5. 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

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

    PubMed

    Bartfai, Tamas; Wang, Ming-wei

    2013-07-01

    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

  7. Positive Classroom Management: A Step-By-Step Guide to Successfully Running the Show without Destroying Student Dignity.

    ERIC Educational Resources Information Center

    DiGiulio, Robert

    This publication provides practical, step-by-step guidance for teachers on becoming more effective in classroom management by using a positive and constructive, rather than negative and punitive, approach to foster prosocial student behavior. The publication is divided into an introduction and three parts. The Introduction examines why effective…

  8. 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

  9. Asphalt Showing Bacterial Degeneration 

    E-print Network

    Unknown

    2011-08-17

    Widely considered in the medical field as the last of the golden anti-microbial drugs, fluorinated quinolones provide a "last defense" for the attack on bacterial infections. The drugs are useful for treating gram negative and some gram positive...

  10. Overall false positive rates in tests for linear trend in tumor incidence in animal carcinogenicity studies of new drugs

    Microsoft Academic Search

    Karl K. Lin; Mohammad A. Rahman

    1998-01-01

    Based on results of simulation and empirical studies conducted within the divisions of biometrics, center for drug evaluation and research, food and drug administration, and in collaboration with the national toxicology program, the center has recently changed the significance levels for testing positive linear trend in incidence rate for common and rare tumors, respectively, from 0.01 and 0.05 to 0.005

  11. 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

  12. 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

  13. 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

  14. College on Problems of Drug Dependence taskforce on prescription opioid non-medical use and abuse: position statement

    Microsoft Academic Search

    James Zacny; George Bigelow; Peggy Compton; Kathleen Foley; Martin Iguchi; Christine Sannerud

    2003-01-01

    This position paper from the College on Problems of Drug Dependence addresses the issues related to non-medical use and abuse of prescription opioids. A central theme throughout is the need to strike a balance between risk management strategies to prevent and deter prescription opioid abuse and the need for physicians and patients to have appropriate access to opioid pharmaceuticals for

  15. Fine granules showing sustained drug release prepared by high-shear melt granulation using triglycerin full behenate and milled microcrystalline cellulose.

    PubMed

    Aoki, Hajime; Iwao, Yasunori; Uchimoto, Takeaki; Noguchi, Shuji; Kajihara, Ryusuke; Takahashi, Kana; Ishida, Masayuki; Terada, Yasuko; Suzuki, Yoshio; Itai, Shigeru

    2015-01-30

    This study aimed to prepare fine granules with a diameter less than 200?m and sustained drug release properties by melt granulation. Triglycerin full behenate (TR-FB) was examined as a new meltable binder (MB) by comparison of its properties with those of glycerin monostearate (GM), widely used as MB. The effect of milling microcrystalline cellulose (MCC), an excipient for melt granulation, on the granule properties was also investigated. TR-FB was more stable during heating and storage than GM, and produced smaller granules with narrower particle size distribution, larger yield in the 106-200?m range, uniform roundness and better sustained drug release profile than those prepared with GM. Granules prepared with milled MCC had almost the same physicochemical properties as those produced with intact MCC. However, milled MCC produced granules with a more rigid structure and smaller void space than intact MCC. Consequently, the granules produced with milled MCC showed better sustained drug release behavior than those prepared with intact MCC. We successfully prepared fine granules with sustained drug release properties and diameter of less than 200?m using TR-FB and milled MCC. PMID:25434591

  16. Experimental Psoriasis Drug Shows Promise

    MedlinePLUS

    ... guselkumab, was compared to the commonly used medication adalimumab (Humira, Enbrel) in a study involving nearly 300 ... treatment, compared to 58 percent of patients taking adalimumab, the researchers reported. However, patients getting guselkumab were ...

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

    SciTech Connect

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    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.

  18. The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst injured drivers and their role in driver culpability: part i: the prevalence of drug use in drive the drug-positive group.

    PubMed

    Longo, M C; Hunter, C E; Lokan, R J; White, J M; White, M A

    2000-09-01

    Blood samples from 2,500 injured drivers were analysed for alcohol, cannabinnoids, benzodiazepines and stimulants. Overall, three-quarters of drivers tested negative for drugs. Alcohol was the most frequently detected drug. Cannabinoids were also detected at high rates, but the majority of drivers tested positive for THC-acid, the inactive metabolite of THC. Benzodiazepines and stimulants were detected at low rates, and detection rates for combinations of drugs were also low. Males were more likely to test positive for drugs, especially alcohol and THC, whereas females were more likely to test positive for benzodiazepines. A similar proportion of car drivers and motorcycle riders tested positive for drugs, although riders were more likely to test positive for THC. Single-vehicle crashes were particularly associated with alcohol for both car driver and riders, and for riders, multiple-vehicle crashes were particularly associated with THC. PMID:10908133

  19. A preliminary study of spiritual self-schema (3-S(+)) therapy for reducing impulsivity in HIV-positive drug users

    Microsoft Academic Search

    Arthur Margolin; Zev Schuman-Olivier; Mark Beitel; Ruth M. Arnold; Carl E. Fulwiler; S. Kelly Avants

    2007-01-01

    The purpose of this study was twofold. First, pretreatment correlations are presented among impulsivity, intoxicant use, HIV risk behavior, spirituality, and motivation in a sample of 38 HIV-positive drug users. Second, treatment outcomes are presented from a preliminary study of spiritual self-schema (3-S(+)) therapy - a manual-guided psychotherapy integrating cognitive and Buddhist psychologies - for increasing motivation for abstinence, HIV

  20. A Tree-Ring Based Reconstruction (1725-present) of the Position of the Summer North Atlantic Jet Shows a 20th Century Northward Shift

    NASA Astrophysics Data System (ADS)

    Trouet, V.; Babst, F.

    2014-12-01

    The position and strength of the Northern Hemisphere polar jet are important modulators of mid-latitude weather extremes and the societal, ecosystem, and economic damage related to them. The position of the North Atlantic jet (NAJ) controls the location of the Atlantic storm track and anomalies in the NAJ position have been related to temperature and precipitation extremes over Europe. In summer, a southern NAJ regime can result in floods in the British Isles (BRIT) and increasing odds of heat waves in the northeastern Mediterranean (NEMED). Variability in the amplitude and speed of the Northern Hemisphere jet stream is hotly debated as a potential mechanism linking recent mid-latitude weather extremes to anthropogenic warming. However, the hypothesis of jet stream variability as a possible mechanism linking Arctic amplification to mid-latitude weather extremes is largely based on data sets with limited temporal extent that do not warrant robust results from a statistical significance perspective. Here, we combined two summer temperature-sensitive tree-ring records from BRIT and NEMED to reconstruct interannual variability in the latitudinal position of the summer NAJ back to 1725. The two well-replicated temperature proxies counter-correlate significantly over the full period and thus illustrate the temperature dipole generated by anomalous NAJ positions. Positive extremes in the NAJ reconstruction correspond to heatwaves recorded in the historical Central England temperature record and negative extremes correspond to reconstructed fire years in Greece. The reconstruction shows a northward shift in the latitudinal NAJ position since the 1930s that is most pronounced in the northern NAJ extremes, suggesting a more frequent occurrence of BRIT hot summers in the 20th century compared to previous centuries.

  1. 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

  2. Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

    Microsoft Academic Search

    Gary D. Friedman; Natalia Udaltsova; James Chan; Charles P. Quesenberry Jr; Laurel A. Habel

    2009-01-01

    Objective  To screen commonly used prescription drugs for possible carcinogenic effects.\\u000a \\u000a \\u000a \\u000a Methods  In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for\\u000a up to 12½ years for incident cancer. Nested case–control analyses of 55 cancer sites and all combined included up to ten matched\\u000a controls per case, with lag of at least 2 years between

  3. 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

  4. New drugs and indications in 2013: little real progress but regulatory authorities take some positive steps.

    PubMed

    2014-04-01

    2013 saw few therapeutic innovations that really benefitted patients; once again, marketing authorisations were too often granted despite inadequate clinical data. The French health authorities implemented a few measures designed to protect patients from dangerous drugs, including market withdrawals, restrictions on use, and delisting. PMID:24860905

  5. Towards Gram-positive antivirulence drugs: New inhibitors of Streptococcus agalactiae Stk1

    Microsoft Academic Search

    Mayalen Oxoby; Franēois Moreau; Lionel Durant; Alexis Denis; Jean-Marie Genevard; Vanida Vongsouthi; Sonia Escaich; Vincent Gerusz

    2010-01-01

    A structure–activity relationship study from a screening hit and structure-based design strategy has led to the identification of bisarylureas as potent inhibitors of Streptococcus agalactiae Stk1. As this target has been directly linked to bacterial virulence, these inhibitors can be considered as a promising step towards antivirulence drugs.

  6. Crenolanib is active against models of drug-resistant FLT3-ITD?positive acute myeloid leukemia

    PubMed Central

    Zimmerman, Eric I.; Turner, David C.; Buaboonnam, Jassada; Hu, Shuiying; Orwick, Shelley; Roberts, Michael S.; Janke, Laura J.; Ramachandran, Abhijit; Stewart, Clinton F.; Inaba, Hiroto

    2013-01-01

    FLT3 kinase internal tandem duplication (ITD) mutations are common in acute myeloid leukemia (AML) and are associated with poor clinical outcomes. Although initial responses to FLT3 tyrosine kinase inhibitors (TKIs) are observed in FLT3-ITD?positive patients, subsequent relapse often occurs upon acquisition of secondary FLT3 kinase domain (KD) mutations, primarily at residues D835 and F691. Using biochemical assays, we determined that crenolanib, a novel TKI, demonstrates type I properties and is active against FLT3 containing ITD and/or D835- or F691-activating mutations. Potent activity was observed in FLT3-ITD?positive AML cell lines. Crenolanib delayed the outgrowth of MV4-11 cells in a xenograft mouse model, whereas in combination with the type II TKI sorafenib, a significant decrease in leukemic burden (P < .001) and prolonged survival (P < .01) was observed compared with either type I or II TKI alone. Crenolanib was active against Ba/F3 cells harboring FLT3-ITD and secondary KD mutations and sorafenib-resistant MOLM-13 cells containing FLT3-ITD/D835Y both in vitro and in vivo. In addition, crenolanib inhibited drug-resistant AML primary blasts with FLT3-ITD and D835H/Y mutations. These preclinical data demonstrate that crenolanib is effective against FLT3-ITD containing secondary KD mutations, suggesting that crenolanib may be a useful therapeutic agent for TKI-naive and drug-resistant FLT3-ITD?positive AML. PMID:24046014

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...707.7 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.7...designated positions. (a)(1) Each workplace substance abuse program will provide for random testing for...

  8. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...707.7 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.7...designated positions. (a)(1) Each workplace substance abuse program will provide for random testing for...

  9. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...707.7 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.7...designated positions. (a)(1) Each workplace substance abuse program will provide for random testing for...

  10. The context of HIV risk behaviours among HIV-positive injection drug users in Viet Nam: Moving toward effective harm reduction

    PubMed Central

    Thanh, Duong Cong; Moland, Karen Marie; Fylkesnes, Knut

    2009-01-01

    Background Injection drug users represent the largest proportion of all HIV reported cases in Viet Nam. This study aimed to explore the perceptions of risk and risk behaviours among HIV-positive injection drug users, and their experiences related to safe injection and safe sex practices. Methods This study used multiple qualitative methods in data collection including in-depth interviews, focus group discussions and participant observation with HIV-positive injection drug users. Results The informants described a change in the sharing practices among injection drug users towards more precautions and what was considered 'low risk sharing', like sharing among seroconcordant partners and borrowing rather than lending. However risky practices like re-use of injection equipment and 'syringe pulling' i.e. the use of left-over drugs in particular, were frequently described and observed. Needle and syringe distribution programmes were in place but carrying needles and syringes and particularly drugs could result in being arrested and fined. Fear of rejection and of loss of intimacy made disclosure difficult and was perceived as a major obstacle for condom use among recently diagnosed HIV infected individuals. Conclusion HIV-positive injection drug users continue to practice HIV risk behaviours. The anti-drug law and the police crack-down policy appeared as critical factors hampering ongoing prevention efforts with needle and syringe distribution programmes in Viet Nam. Drastic policy measures are needed to reduce the very high HIV prevalence among injection drug users. PMID:19348681

  11. 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

  12. Positive Selection Detection in 40,000 Human Immunodeficiency Virus (HIV) Type 1 Sequences Automatically Identifies Drug Resistance and Positive Fitness Mutations in HIV Protease and Reverse Transcriptase

    Microsoft Academic Search

    Lamei Chen; Alla Perlina; Christopher J. Lee

    2004-01-01

    Drug resistance is a major problem in the treatment of AIDS, due to the very high mutation rate of human immunodeficiency virus (HIV) and subsequent rapid development of resistance to new drugs. Identification of mutations associated with drug resistance is critical for both individualized treatment selection and new drug design. We have performed an automated mutation analysis of HIV Type

  13. Perceptions of community and family level IDU and HIV related stigma, disclosure decisions and experiences with layered stigma among HIV positive injection drug users in Vietnam

    PubMed Central

    Rudolph, A.E.; Davis, W.W.; Quan, V.M.; Ha, T.V.; Minh, N.L.; Gregowski, A.; Salter, Megan; Celentano, D.D.; Go, V.

    2012-01-01

    This paper explores how perceived stigma and layered stigma related to injection drug use and being HIV positive influence the decision to disclose one’s HIV status to family and community and experiences with stigma following disclosure among a population of HIV positive male injection drug users (IDUs) in Thai Nguyen, Vietnam. In qualitative interviews conducted between 2007 and 2008, 25 HIV positive male IDUs described layered stigma in their community but an absence of layered stigma within their families. These findings suggest the importance of community level HIV prevention interventions that counter stigma and support families caring for HIV positive relatives. PMID:21777075

  14. Introduction of chromosome segment carrying the seed storage protein genes from chromosome 1V of Dasypyrum villosum showed positive effect on bread-making quality of common wheat.

    PubMed

    Ruiqi, Zhang; Mingyi, Zhang; Xiue, Wang; Peidu, Chen

    2014-03-01

    Development of wheat- D. villosum 1V#4 translocation lines; physically mapping the Glu - V1 and Gli - V1 / Glu - V3 loci; and assess the effects of the introduced Glu - V1 and Gli - V1 / Glu - V3 on wheat bread-making quality. Glu-V1 and Gli-V1/Glu-V3 loci, located in the chromosome 1V of Dasypyrum villosum, were proved to have positive effects on grain quality. However, there are very few reports about the transfer of the D. villosum-derived seed storage protein genes into wheat background by chromosome manipulation. In the present study, a total of six CS-1V#4 introgression lines with different alien-fragment sizes were developed through ionizing radiation of the mature female gametes of CS--D. villosum 1V#4 disomic addition line and confirmed by cytogenetic analysis. Genomic in situ hybridization (GISH), chromosome C-banding, twelve 1V#4-specific EST-STS markers and seed storage protein analysis enabled the cytological physical mapping of Glu-V1 and Gli-V1/Glu-V3 loci to the region of FL 0.50-1.00 of 1V#4S of D. villosum. The Glu-V1 allele of D. villosum was Glu-V1a and its coded protein was V71 subunit. Quality analysis indicated that Glu-V1a together with Gli-V1/Glu-V3 loci showed a positive effect on protein content, Zeleny sedimentation value and the rheological characteristics of wheat flour dough. In addition, the positive effect could be maintained when specific Glu-V1 and Gli-V1/Glu-V3 loci were transferred to the wheat genetic background as in the case of T1V#4S-6BS · 6BL, T1V#4S · 1BL and T1V#4S · 1DS translocation lines. These results showed that the chromosome segment carrying the Glu-V1 and Gli-V1/Glu-V3 loci in 1V#4S of D. villosum had positive effect on bread-making quality, and the T1V#4S-6BS · 6BL and T1V#4S · 1BL translocation lines could be useful germplasms for bread wheat improvement. The developed 1V#4S-specific molecular markers could be used to rapidly identify and trace the alien chromatin of 1V#4S in wheat background. PMID:24408374

  15. False-positive tests for syphilis associated with human immunodeficiency virus and hepatitis B virus infection among intravenous drug abusers. Valencian Study Group on HIV Epidemiology.

    PubMed

    Hernįndez-Aguado, I; Bolumar, F; Moreno, R; Pardo, F J; Torres, N; Belda, J; Espacio, A

    1998-11-01

    The role of HIV, hepatitis C virus, and hepatitis B virus infections in the production of biological false-positive reactions for syphilis was evaluated in two large samples of intravenous drug abusers and homosexual men attending AIDS prevention centers in Spain. A significantly increased odds ratio (OR) for false-positive tests for syphilis [OR 2.23, 95% confidence intervals (CI) 1.76-2.83] was observed for HIV-seropositive intravenous drug abusers; biological false-positive reactions were also more frequent (OR 1.73, 95% CI 1.30-2.31) among intravenous drug abusers who were hepatitis B virus seropositive but not among those who were hepatitis C virus seropositive (OR 0.90; 95% CI 0.48-1.69). Among homosexuals, the association between HIV and biological false-positive reactions was restricted to subjects who were also intravenous drug abusers, indicating the crucial role of intravenous drug abuse. Only 20.5% of intravenous drug abusers with a previous biological false-positive reaction yielded a false-positive result in their subsequent visit. PMID:9923520

  16. Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

    Microsoft Academic Search

    Rajesh Gupta; Jennifer L. Beck; Stephen F. Ralph; Margaret M. Sheil; Janice R. Aldrich-Wright

    2004-01-01

    Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin,\\u000a Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from

  17. Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.

    PubMed

    Ko, Bong-Kook; Lee, Sook-Yeon; Lee, Young-Ha; Hwang, In-Sik; Persson, Helena; Rockberg, Johan; Borrebaeck, Carl; Park, Dongeun; Kim, Kyu-Tae; Uhlen, Mathias; Lee, Jong-Seo

    2015-02-01

    The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer. Here, we describe the development of 1E11, a HER2-targeted humanized monoclonal antibody showing increased efficacy in a highly synergistic manner in combination with trastuzumab in the HER2-overexpressing gastric cancer cell lines NCI-N87 and OE-19. The two antibodies bind to sub-domain IV of the receptor, but have non-overlapping epitopes, allowing them to simultaneously bind HER2. Treatment with 1E11 alone induced apoptosis in HER2-positive cancer cells, and this effect was enhanced by combination treatment with trastuzumab. Combination treatment with 1E11 and trastuzumab reduced the levels of total HER2 protein and those of aberrant HER2 signaling molecules including phosphorylated HER3 and EGFR. The synergistic antitumor activity of 1E11 in combination with trastuzumab indicates that it could be a novel potent therapeutic antibody for the treatment of HER2-overexpressing gastric cancers. PMID:25306393

  18. The effect of methadone on immunological parameters among HIV-positive and HIV-negative drug users.

    PubMed

    Carballo-Diéguez, A; Sahs, J; Goetz, R; el Sadr, W; Sorell, S; Gorman, J

    1994-08-01

    Our objective was to assess the effects of methadone use on immune parameters. A convenience sample of men and women drug injectors who knew their HIV serostatus were enrolled in a longitudinal observational study of HIV illness. During analysis of baseline data, differences were noted in immune parameters among Methadone users. Study participants were recruited in Manhattan, New York, from a methadone maintenance clinic, and infectious disease clinic of an inner city hospital, and a drug-free community center. The participants were 220 men and women, current or former drug injectors, approximately half of them HIV-antibody positive and the rest HIV-antibody negative. Candidates with opportunistic infections and secondary neoplasms were excluded. Methadone users were compared to nonmethadone users for absolute and percentage counts of CD4, CD8, and activated T lymphocytes; CD4/CD8 ratio; an HIV symptom check list; and medical staging. The results discussed in this paper were formulated after data collection was complete. Our data indicate that methadone treatment, while not significantly affecting absolute CD4 lymphocyte count, is associated with a lower CD4 percentage and CD4/CD8 cell ratio, and with a higher CD8 absolute count and percentage. These differences are present regardless of HIV serostatus. Our findings should be interpreted with caution since we did not set out to investigate the effects of methadone on the immune system. Nevertheless, if it is corroborated that methadone has a detrimental effect on the immune system, finding alternatives to methadone-maintenance treatment for drug injectors will be a necessity. PMID:7977217

  19. Daptomycin: a new drug class for the treatment of Gram-positive infections.

    PubMed

    Alder, Jeffrey D

    2005-02-01

    Daptomycin is the first member of a new class of bactericidal antibiotics, the cyclic lipopeptides. In September 2003, daptomycin was approved for the treatment of Gram-positive infections associated with complicated skin and skin structure infections. A key feature of daptomycin is its rapid, concentration-dependent bactericidal activity against significant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, glycopeptide-intermediate and -resistant S. aureus and vancomycin-resistant Enterococcus faecalis and Enterococcus faecium (VRE). Daptomycin also has a unique mechanism of action, no cross-resistance with any other class of antibiotic and a relatively prolonged concentration-dependent postantibiotic effect in vitro. In the United States, daptomycin has been approved for use at a dose of 4 mg/ kg once daily in the treatment of S. aureus (including methicillin-resistant strains), three beta-hemolytic streptococci (S. pyogenes, S. agalactiae and S. dysgalactiae subsp. equisimilis) and E. faecalis associated with complicated skin and skin structure infections. In addition, daptomycin is undergoing a phase III evaluation for the treatment of bacteremia and endocarditis due to S. aureus. With its once-daily dosing, favorable safety profile and low potential for resistance, daptomycin is a powerful new antibiotic therapy against Gram-positive infections. PMID:15821781

  20. Do Health Professionals have Positive Perception Towards Consumer Reporting of Adverse Drug Reactions?

    PubMed Central

    Alshakka, Mohammed Ahmed; Ibrahim, Mohamed Izham Mohamed; Hassali, Mohamed Azmi Ahmad

    2013-01-01

    Aim: The aim of this study was to evaluate the perceptions of general practitioners (GPs) and community pharmacists (CPs) in Penang, Malaysia, towards consumer reporting of Adverse Drug Reactions (ADRs). Methodology: A cross-sectional mail survey was adopted for the performance of the study. Survey questionnaires were sent to 192 CPs and 400 GPs in the state of Penang, Malaysia. Reminders were sent to all the non-respondents after 3 weeks of the initial mailing. Data which were collected from the questionnaires were analyzed by using the Statistical Package for Social Science (SPSS), version 15. The Chi-square test was used to determine as to whether there was any significant difference between expected and observed frequencies at the alpha level of 0.05. Results: Only 104 respondents (47 CPs and 57 GPs) returned the survey, with a response rate of 18.0%- a figure which could be considered to be low. This study indicated that GPs and CPs were aware about the importance and benefits of consumer reporting. A majority of them (88.0%) thought that consumer reporting would add more benefits to the existing pharmacovigilance program. Similarly, 97% of the respondents agreed that reporting of ADRs was necessary and 87.0% respondents had seen ADRs among their patients. However, 57 of them (6.0%), had not been aware that the national program in Malaysia allowed consumers to report ADRs. A majority of them (97.0%) agreed that consumers needed more education regarding ADR reporting. Most of them (84.0%) thought that consumers could not write valid reports which were similar to reports which were made by healthcare professionals (HCPs). A majority of the respondents (68.0%) had not heard about the consumer reporting program in Malaysia and half of them did not believe that consumer reporting could overcome under-reporting, which was the main problem of the national pharmacovigilance program in Malaysia. Conclusion: The GPs and CPs were aware about the importance and benefits of consumer reporting. Such reporting will add more benefits to the existing programmes in Malaysia, although the barrier that we are facing now is the doubt that they hold over patients’ ability to write valid reports which are similar to reports which are made by healthcare professionals (HCPs). Therefore, the consumers need to be educated more about their medications, on how to validate any complaints that they had about the drug consumption and on how to file a proper report and channel it to the ‘right’ person or bodies. Equally importantly, the media and the non-governmental organizations (NGOs) should play an important role in determining the success of consumer reporting. PMID:24298470

  1. UNDERLYING PATHOPHYSIOLOGY OF HCV INFECTION IN HIV-POSITIVE DRUG USERS

    PubMed Central

    Balasubramanian, Anuradha; Groopman, Jerome E.; Ganju, Ramesh K.

    2009-01-01

    HCV and HIV infections are very common among injection drug users (IDUs). It is well known that 80–90% of HIV-infected IDUs are also infected with HCV. Furthermore, patients with HCV/HIV co-infection are at a higher risk of progressing to end-stage liver disease, namely cirrhosis. Even though there is increasing global awareness of HCV/HIV co-infection and extended therapeutic programs for this infected population, little is known about the HCV/HIV pathophysiology that mediates the rapid progression to hepatic disease. Liver disease caused by HCV/HIV co-infection is characterized by inflammation and cell-death. Recent reports suggest that the HIV and HCV envelope proteins may induce apoptosis and inflammation in hepatocytes via a novel pathway involving collaborative signaling. Moreover, HCV/HIV co-infection may also alter the cytokine production in vivo. Further studies to elucidate the molecular mechanisms of HCV and HIV-mediated pathogenesis will help in the development of therapeutic strategies against HCV/HIV co-infection in these patients. PMID:18681194

  2. Role of 5HT 2A and 5HT 2C receptors in the stimulus effects of hallucinogenic drugs II: reassessment of LSD false positives

    Microsoft Academic Search

    David Fiorella; R. A. Rabin; J. C. Winter

    1995-01-01

    In the context of animal studies of hallucinogens, an LSD-false positive is defined as a drug known to be devoid of hallucinogenic activity in humans but which nonetheless fully mimics LSD in animals. Quipazine, MK-212, lisuride, and yohimbine have all been reported to be LSD false positives. The present study was designed to determine whether these compounds also substitute for

  3. 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

    flush 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... the interest in the subject grow exponen- tially. Brooks recalls earlier days when he and colleague Dr. Kevin Chambliss, a Baylor chemistry professor, were among the few researchers studying this topic?compared This is your stream on drugs continued tx...

  4. 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

    flush 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... the interest in the subject grow exponen- tially. Brooks recalls earlier days when he and colleague Dr. Kevin Chambliss, a Baylor chemistry professor, were among the few researchers studying this topic?compared This is your stream on drugs continued tx...

  5. Two recombinant peptides, SpStrongylocins 1 and 2, from Strongylocentrotus purpuratus, show antimicrobial activity against Gram-positive and Gram-negative bacteria.

    PubMed

    Li, Chun; Blencke, Hans-Matti; Smith, L Courtney; Karp, Matti T; Stensvåg, Klara

    2010-03-01

    The cysteine-rich strongylocins were the first antimicrobial peptides (AMPs) discovered from the sea urchin species, Strongylocentrotus droebachiensis. Homologous putative proteins (called SpStrongylocin) were found in the sister species, S. purpuratus. To demonstrate that they exhibit the same antibacterial activity as strongylocins, cDNAs encoding the 'mature' peptides (SpStrongylocins 1 and 2) were cloned into a direct expression system fusing a protease cleavage site and two purification tags to the recombinant peptide. Both recombinant fusion peptides were expressed in a soluble form in an Escherichia coli strain tolerant to toxic proteins. Enterokinase was used to remove the fusion tags and purified recombinant SpStrongylocins 1 and 2 showed antimicrobial activity against both Gram-negative and Gram-positive bacteria. The results of membrane integrity assays against cytoplasmic membranes of E. coli suggest that both recombinant SpStrongylocins 1 and 2 conduct their antibacterial activity by intracellular killing mechanisms because no increase in membrane permeability was detected. PMID:19852980

  6. Budget impact analysis of antiretroviral less drug regimen simplification in HIV-positive patients on the Italian National Health Service

    PubMed Central

    Restelli, Umberto; Andreoni, Massimo; Antinori, Andrea; Bonfanti, Marzia; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Rizzardini, Giuliano; Croce, Davide

    2014-01-01

    Background Deintensification and less drug regimen (LDR) antiretroviral therapy (ART) strategies have proved to be effective in terms of maintaining viral suppression in human immunodeficiency virus (HIV)-positive patients, increasing tolerability, and reducing toxicity of antiretroviral drugs administered to patients. However, the economic impact of these strategies have not been widely investigated. The aim of the study is to evaluate the economic impact that ART LDR could have on the Italian National Health Service (INHS) budget. Methods A budget impact model was structured to assess the potential savings for the INHS by the use of ART LDR for HIV-positive patients with a 3 year perspective. Data concerning ART cost, patient distribution within different ARTs, and probabilities for patients to change ART on a yearly basis were collected within four Italian infectious diseases departments, providing ART to 13.7% of the total number of patients receiving ART in Italy. Results The LDR investigated (protease inhibitor-based dual and monotherapies) led to savings for the hospitals involved when compared to the “do nothing” scenario on a 3 year basis, between 6.7% (23.11 million €) and 12.8% (44.32 million €) of the total ART expenditures. The mean yearly cost per patient is reduced from 9,875 € in the do nothing scenario to a range between 9,218 € and 8,615 €. The use of these strategies within the four departments involved would have led to a reduction of ART expenditures for the INHS of between 1.1% and 2.1% in 3 years. Conclusion ART LDR simplification would have a significant impact in the reduction of ART-related costs within the hospitals involved in the study. These strategies could therefore be addressed as a sustainable answer to the public financing reduction observed within the INHS in the last year, allowing therapies to be dispensed without affecting the quality of the services provided. PMID:25285019

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

    E-print Network

    Nizet, Victor

    (MRSA). The eight compound mixtures exhibiting bactericidal activity (10 lg/mL) against MRSA were used to direct the synthesis of 36 individual compounds that were then screened for activity against MRSA individual compounds were bactericidal for MRSA at 62.5 lg/mL, with a subset of these compounds showing

  8. Positive feedback between oncogenic KRAS and HIF-1? confers drug resistance in colorectal cancer

    PubMed Central

    Wang, Yanzhao; Lei, Fuming; Rong, Wanshui; Zeng, Qingmin; Sun, Wenbing

    2015-01-01

    Approximately 30%–50% of colorectal cancers (CRCs) harbor the somatic mutated KRAS gene. KRAS G12V, one of the most common KRAS mutations in CRCs, is linked to increased tumor aggressiveness, less response to anti-epidermal growth factor receptor (EGFR) therapy, and poor survival rate. In this study, we sought to determine whether resistance to EGFR inhibitors in colorectal cancer cells harboring KRAS G12V mutation is associated with hypoxia. Our data indicated that HIF-1? was induced by KRAS G12V signaling at transcription level. Hypoxia or HIF-1? overexpression could increase KRAS G12V activity. Therefore, a positive feedback between hypoxia and KRAS G12V activation was formed. Cetuximab, an EGFR inhibitor, which has a minor effect on KRAS-mutant CRCs, could effectively inhibit the proliferation of CRC cells harboring KRAS G12V mutation when combined with HIF-1? inhibitor PX-478. Our data indicated that hypoxia was involved in resistance to anti-EGFR therapy, and a combination therapy might be necessary for CRC patients with KRAS mutation.

  9. Drug assertiveness and sexual risk-taking behavior in a sample of HIV-positive, methamphetamine-using men who have sex with men.

    PubMed

    Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; McQuaid, John R; Patterson, Thomas L

    2011-10-01

    Drug assertiveness skills have been demonstrated to be effective in reducing substance use behaviors among patients with alcohol or heroin use disorders. This study examined the association between drug assertiveness and methamphetamine use, psychological factors, and sexual risk behaviors in a sample of 250 HIV-positive men who have sex with men enrolled in a safer sex intervention in San Diego, CA. Less assertiveness in turning down drugs was associated with greater frequency and larger amounts of methamphetamine use, lower self-esteem, higher scores on a measure of sexual sensation seeking, and greater attendance at risky sexual venues. These data suggest that drug assertiveness training should be incorporated into drug abuse treatment programs and other risk reduction interventions for methamphetamine users. PMID:21550758

  10. Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients

    PubMed Central

    Prinz, Philip; Hofmann, Tobias; Ahnis, Anne; Elbelt, Ulf; Goebel-Stengel, Miriam; Klapp, Burghard F.; Rose, Matthias; Stengel, Andreas

    2015-01-01

    Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5–25 kg/m2), underweight (anorexia nervosa, BMI < 17.5 kg/m2) and overweight (obesity with BMI 30–40, 40–50 and >50 kg/m2, n = 14–15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6 ± 0.3 kg/m2, n = 43). Lastly, in a population of obese patients (BMI 48.5 ± 0.9 kg/m2, n = 85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r = 0.26, p = 0.03) in the population of patients with broad range of BMI (9–85 kg/m2, n = 74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p > 0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r = ?0.30, p = 0.008), while no associations were observed with other psychometric eating behavior-related parameters (p > 0.05) in obese patients. In conclusion, these data may point toward a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating.

  11. Hospital length of stay in individuals with schizophrenia with and without cocaine-positive urine drug screens at hospital admission.

    PubMed

    Wu, Hanjing Emily; Mohite, Satyajit; Ngana, Ikenna; Burns, Wilma; Shah, Nurun; Schneider, Laurie; Schmitz, Joy M; Lane, Scott D; Okusaga, Olaoluwa O

    2015-01-01

    Despite the high prevalence of cocaine use disorder (CUD) in individuals with schizophrenia, current understanding of the effect of cocaine on psychiatric hospital length of stay (LOS) in individuals with schizophrenia is limited. We therefore retrospectively examined the medical records of 5106 hospital admissions due to exacerbation of schizophrenia. Linear regression and t-test were used to compare LOS between individuals with schizophrenia with cocaine-positive urine drug test results and those with negative test results. Individuals with schizophrenia who were also positive for cocaine had shorter LOS from both unadjusted (geometric mean LOS, 8.07 ± 1.92 vs. 11.83 ± 1.83 days; p < 0.001) and adjusted (? = 0.69; confidence interval, 0.63-0.76; p < 0.001) analyses. Our results suggest that individuals with schizophrenia who also have comorbid CUD may require shorter inpatient treatment during periods of exacerbation of symptoms. Replication of this finding has relevance in treatment planning and resource allocation for the subpopulation of individuals with schizophrenia who also have stimulant use disorders. PMID:25489749

  12. Predictors of Weight Change in Male HIV-Positive Injection Drug Users Initiating Antiretroviral Therapy in Hanoi, Vietnam

    PubMed Central

    Tang, Alice M.; Sheehan, Heidi B.; Jordan, Michael R.; Duong, Dang Van; Terrin, Norma; Dong, Kimberly; Lien, Trinh Thi Minh; Trung, Nguyen Vu; Wanke, Christine A.; Hien, Nguyen Duc

    2011-01-01

    We examined clinical and nutritional predictors of weight change over two consecutive 6-month intervals among 99 HIV-positive male injection drug users initiating antiretroviral therapy (ART) in Hanoi, Vietnam. The average weight gain was 3.1 ± 4.8?kg in the first six months after ART and 0.8 ± 3.0?kg in the following six months. Predictors of weight change differed by interval. In the first interval, CD4 < 200?cells/?L, excellent/very good adherence to ART, bothersome nausea, and liquid supplement use were all associated with positive weight changes. Moderate to heavy alcohol use and tobacco smoking were associated with negative weight changes. In the second interval, having a CD4 count <200?cells/?L at the beginning of the interval and tobacco smoking were the only significant predictors and both were associated with negative weight changes. We identified several potential areas for interventions to promote weight gain immediately after starting ART in this population. Studies are needed to determine whether improving weight prior to, or at, ART initiation will result in improved outcomes on ART. PMID:21776380

  13. Definition of the "Drug-Angiogenic-Activity-Index" that allows the quantification of the positive and negative angiogenic active drugs: a study based on the chorioallantoic membrane model.

    PubMed

    Demir, Resit; Peros, Georgios; Hohenberger, Werner

    2011-06-01

    Since the introduction of the angiogenic therapy by Folkman et al. in the 1970'ies many antiangiogenic drugs were identified. Only few of them are still now in clinical use. Also the Vascular Endothelial Growth Factor (VEGF), the cytokine with the highest angiogenic activity, has been identified. Its antagonist, Bevacizumab, is produced and admitted for the angiogenic therapy in first line for metastatic colorectal cancer. When we look at preclinical studies, they fail of in vivo models that define the "Drug-Angiogenic-Activity-Index" of angiogenic or antiangiogenic drugs. This work proposes a possible standardized procedure to define the "Drug Angiogenic Activity Index" by counting the vascular intersections (VIS) on the Chorioallantoic Membrane after drug application. The equation was defined as follows: {?VIS[Drug]-?VIS[Control]} / ? VIS[Control]. For VEGF a Drug-Angiogenic-Activity-Index of 0.92 was found and for Bevacizumab a -1. This means almost that double of the naturally angiogenic activity was achieved by VEGF on the Chorioallantoic membrane. A complete blocking of naturally angiogenic activity was observed after Bevacizumabs application. Establishing the "Drug-Angiogenic-Activity-Index" in the preclinical phase will give us an impact of effectiveness for the new constructed antiangiogenic drugs like the impact of effectiveness in the cortisone family. PMID:21221880

  14. Cost-effectiveness of integrating methadone maintenance and antiretroviral treatment for HIV-positive drug users in Vietnam's injection-driven HIV epidemics.

    PubMed

    Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Nguyen, Long Thanh; Vu, Phu Xuan; Mills, Steve; Houston, Stan; Jacobs, Philip

    2012-10-01

    Drug use negatively affects adherence to and outcomes of antiretroviral treatment (ART). This study evaluated the cost-effectiveness of integrating methadone maintenance treatment (MMT) with ART for HIV-positive drug users (DUs) in Vietnam. A decision analytical model was developed to compare the costs and consequences of 3 HIV/AIDS treatment strategies for DUs: (1) only ART, (2) providing ART and MMT in separated sites (ART-MMT), and (3) integrating ART and MMT with direct administration (DAART-MMT). The model was parameterized using empirical data of costs and outcomes extracted from the MMT and ART cohort studies in Vietnam, and international published sources. Probabilistic sensitivity analysis was conducted to examine the model's robustness. The base-case analysis showed that the cost-effectiveness ratio of ART, DAART-MMT, and ART-MMT strategies was USD 1358.9, 1118.0 and 1327.1 per 1 Quality-Adjusted Life Year (QALY), equivalent to 1.22, 1.00, and 1.19 times Gross Domestic Product per capita (GDPpc). The incremental cost-effectiveness ratio for DAART-MMT and ART-MMT versus ART strategy was 569.4 and 1227.8, approximately 0.51 and 1.10 times GDPpc/QALY. At the willingness to pay threshold of 3 times GDPpc, the probability of being cost-effective of DAART-MMT versus ART was 86.1%. These findings indicated that providing MMT along with ART for HIV-positive DUs is a cost-effective intervention in Vietnam. Integrating MMT and ART services could facilitate the use of directly observed therapy that supports treatment adherence and brings about clinically important improvements in health outcomes. This approach is also incrementally cost-effective in this large injection-driven HIV epidemic. PMID:22436971

  15. Drug-Tolerant Cancer Cells Show Reduced Tumor-Initiating Capacity: Depletion of CD44+ Cells and Evidence for Epigenetic Mechanisms

    Microsoft Academic Search

    Hong Yan; Xin Chen; Qiuping Zhang; Jichao Qin; Hangwen Li; Can Liu; Tammy Calhoun-Davis; Luis Della Coletta; Jim Klostergaard; Izabela Fokt; Stanislaw Skora; Waldemar Priebe; Yongyi Bi; Dean G. Tang; Amit Singh

    2011-01-01

    Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide,

  16. Triethyl-n-Hexylammonium Triethyl-n-Hexylboride: a New Antimicrobial Showing Activity Against Candida albicans and Gram-Positive Bacteria

    PubMed Central

    Rosenthal, K. S.; Storm, D. R.; Ford, W. T.

    1975-01-01

    The organic salt triethyl-n-hexylammonium triethyl-n-hexylboride (N2226B2226) has biostatic effects against two gram-positive bacteria, Bacillus subtilis and Micrococcus luteus, and the yeast Candida albicans. Escherichia coli and chicken embryo fibroblasts grown in tissue culture are more refractory to this compound. Images PMID:811160

  17. Recurrent Gastrointestinal Hemorrhage in Treatment with Dasatinib in a Patient Showing SMAD4 Mutation with Acute Lymphoblastic Leukemia Philadelphia Positive and Juvenile Polyposis Hereditary Hemorrhagic Telangiectasia Syndrome.

    PubMed

    Sartor, Chiara; Papayannidis, Cristina; Chiara Abbenante, Maria; Iacobucci, Ilaria; Broccoli, Alessandro; Venturi, Claudia; Testoni, Nicoletta; Ferrari, Anna; Martinelli, Giovanni

    2013-06-28

    We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia. PMID:23888243

  18. Pavlovian drug discrimination with bupropion as a feature positive occasion setter: Substitution by methamphetamine and nicotine, but not cocaine

    PubMed Central

    Wilkinson, Jamie L.; Li, Chia; Bevins, Rick A.

    2010-01-01

    Bupropion can serve as a discriminative stimulus (SD) in an operant drug discrimination task, and a variety of stimulants substitute for the bupropion SD. There are no reports, however, of bupropion functioning as a Pavlovian occasion setter (i.e., feature positive modulator). The present experiment seeks to fill this gap in the literature by training bupropion in rats as a feature positive modulator that disambiguates when a light will be paired with sucrose. Specifically, on bupropion (10 mg/kg IP) sessions, offset of 15-sec cue lights were followed by brief delivery of liquid sucrose; saline sessions were similar except no sucrose was available. Rats readily acquired the discrimination with more conditioned responding to the light on bupropion sessions. Bupropion is approved for use as a smoking cessation aid, and more recently has drawn attention as a potential pharmacotherapy for cocaine and methamphetamine abuse. Accordingly, after discrimination training we tested the ability of cocaine (1 to 10 mg/kg), methamphetamine (0.1 to 1 mg/kg), and nicotine (0.00625 to 0.2 mg/kg) to substitute for the bupropion feature. Nicotine (0.05 mg/kg) and methamphetamine (0.3 mg/kg) substituted fully for bupropion; cocaine did not substitute. These results extend previous research on shared stimulus properties between bupropion and other stimulants to a Pavlovian occasion setting function. Further, this is the first report of nicotine and methamphetamine substitution for bupropion. The overlap in stimulus properties might explain the effectiveness of bupropion as a smoking cessation aid and highlight the possible utility of bupropion for treatment of stimulant use disorder. PMID:19076926

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

    Microsoft Academic Search

    M. A. Kedda; G. Stevens; P. Manga; C. Viljoen; T. Jenkins; M. Ramsay

    1994-01-01

    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

  20. Novel imidazoline antimicrobial scaffold that inhibits DNA replication with activity against mycobacteria and drug resistant Gram-positive cocci.

    PubMed

    Harris, Kendra K; Fay, Allison; Yan, Han-Guang; Kunwar, Pratima; Socci, Nicholas D; Pottabathini, Narender; Juventhala, Ramakrishna R; Djaballah, Hakim; Glickman, Michael S

    2014-11-21

    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

  1. Positive direct antiglobulin tests and haemolytic anaemia following therapy with beta-lactamase inhibitor containing drugs may be associated with nonimmunologic adsorption of protein onto red blood cells.

    PubMed

    Garratty, G; Arndt, P A

    1998-03-01

    A high incidence (39%) of positive direct antiglobulin tests (DATs) has been reported in patients taking Unasyn [ampicillin sodium plus sulbactam sodium (a beta-lactamase inhibitor)]. Three of four patients, with positive DATs, receiving Unasyn or Timentin [ticarcillin disodium plus clavulanate potassium (also a beta-lactamase inhibitor)] developed a haemolytic anaemia (HA) associated with a positive DAT, which resolved when drug therapy was stopped. The patients' sera did not react with red blood cells (RBCs) in the presence of Unasyn or Timentin, but when drug-treated RBCs were tested, patients' sera and normal sera reacted equally by indirect antiglobulin test. Following incubation in normal sera, RBCs treated with Unasyn, Timentin, Augmentin (amoxicillin + clavulanate), sulbactam and clavulanate reacted with anti-human globulin and anti-human albumin (an index of non-specific adsorption); RBCs treated with ampicillin and amoxicillin were nonreactive. The beta-lactamase inhibitors sulbactam and clavulanate seem to cause nonimmunologic adsorption of protein onto RBCs in vitro. This may explain the high incidence of positive DATs detected in patients taking Unasyn, which contains sulbactam. It was not possible to prove that there was a direct association between the nonspecific uptake of protein onto drug-treated RBCs in vitro with the positive DATs or the HA. PMID:9531349

  2. Antipsychotic Drug-Like Effects of the Selective M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator VU0152100

    PubMed Central

    Byun, Nellie E; Grannan, Michael; Bubser, Michael; Barry, Robert L; Thompson, Analisa; Rosanelli, John; Gowrishankar, Raajaram; Kelm, Nathaniel D; Damon, Stephen; Bridges, Thomas M; Melancon, Bruce J; Tarr, James C; Brogan, John T; Avison, Malcolm J; Deutch, Ariel Y; Wess, Jürgen; Wood, Michael R; Lindsley, Craig W; Gore, John C; Conn, P Jeffrey; Jones, Carrie K

    2014-01-01

    Accumulating evidence suggests that selective M4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M4 activators were unsuccessful because of the lack of M4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M4 positive allosteric modulator (PAM) that exerts central effects after systemic administration. We now report that VU0152100 dose-dependently reverses amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M4 KO mice. VU0152100 also blocks amphetamine-induced disruption of the acquisition of contextual fear conditioning and prepulse inhibition of the acoustic startle reflex. These effects were observed at doses that do not produce catalepsy or peripheral adverse effects associated with non-selective mAChR agonists. To further understand the effects of selective potentiation of M4 on region-specific brain activation, VU0152100 alone and in combination with amphetamine were evaluated using pharmacologic magnetic resonance imaging (phMRI). Key neural substrates of M4-mediated modulation of the amphetamine response included the nucleus accumbens (NAS), caudate-putamen (CP), hippocampus, and medial thalamus. Functional connectivity analysis of phMRI data, specifically assessing correlations in activation between regions, revealed several brain networks involved in the M4 modulation of amphetamine-induced brain activation, including the NAS and retrosplenial cortex with motor cortex, hippocampus, and medial thalamus. Using in vivo microdialysis, we found that VU0152100 reversed amphetamine-induced increases in extracellular dopamine levels in NAS and CP. The present data are consistent with an antipsychotic drug-like profile of activity for VU0152100. Taken together, these data support the development of selective M4 PAMs as a new approach to the treatment of psychosis and cognitive impairments associated with psychiatric disorders such as schizophrenia. PMID:24442096

  3. 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.

  4. 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

  5. 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

  6. "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…

  7. 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

  8. Sci Show

    NSDL National Science Digital Library

    The Sci Show, an entertaining series of quirky YouTube videos, tackles topics ranging from ā??How Do Polarized Sunglasses Workā?¯ to ā??Strong Interaction: The Four Fundamental Forces of Physics.ā?¯ Most episodes are less than five minutes long, but they pack a wallop of handy science info. Anyone short on time but long on big questions will benefit from the series. Episodes will be helpful to teachers and parents looking to spark enthusiasm in young minds. Viewers may want to start with recent episodes like ā??Todayā??s Mass Extinction,ā?¯ and the ā??Worldā??s First See-Through Animalā?¯ and ā??How Do Animals Change Color?ā?¯ before digging into the archives for gems like ā??The Truth About Gingersā?¯ and ā??The Science of Lying.ā?¯

  9. NrCAM in Addiction Vulnerability: Positional Cloning, Drug-Regulation, Haplotype-Specific Expression, and Altered Drug Reward in Knockout Mice

    Microsoft Academic Search

    Hiroki Ishiguro; Qing-Rong Liu; Jian-Ping Gong; Frank Scott Hall; Hiroshi Ujike; Marisela Morales; Takeshi Sakurai; Martin Grumet; George R Uhl

    2006-01-01

    Several lines of evidence support roles for the cell adhesion molecule NrCAM in addictions. Fine mapping within a chromosome 7 region that contains previously linked and associated genomic markers identifies NrCAM haplotypes that are associated with substance abuse vulnerabilities in four samples of abusers and controls. Differential display identifies NrCAM as a drug regulated gene. NrCAM is expressed in neurons

  10. Interactive ``Video Doctor'' Counseling Reduces Drug and Sexual Risk Behaviors among HIV-Positive Patients in Diverse Outpatient Settings

    Microsoft Academic Search

    Paul Gilbert; Daniel Ciccarone; Stuart A. Gansky; David R. Bangsberg; Kathleen Clanon; Stephen J. McPhee; Sophia H. Calderón; Alyssa Bogetz; Barbara Gerbert; Landon Myer

    2008-01-01

    BackgroundReducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission. Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks, it is unknown how to best provide “prevention with positives” in clinical settings. Positive Choice, an interactive, patient-tailored computer program, was developed in the

  11. New Drug Shows Potential for Blood Cancer

    MedlinePLUS

    ... or life-threatening conditions. Elotuzumab, administered by intravenous infusion, targets a protein called SLAMF7, which is found ... blood cells and platelets, fatigue and diarrhea. Mild infusion reactions occurred after the first few doses in ...

  12. Resistance to antiretroviral drugs in newly diagnosed, young treatment-naļve HIV-positive pregnant women in the province of KwaZulu-Natal, South Africa.

    PubMed

    Parboosing, R; Naidoo, A; Gordon, M; Taylor, M; Vella, V

    2011-09-01

    In 2004, KwaZulu-Natal initiated one of the world's largest HIV/AIDS treatment programs. Studies in South Africa have shown that patients on antiretroviral therapy (ART) develop rapidly and transmit drug resistant mutations. Since resistance testing is not widely available in Kwazulu-Natal, the Department of Health conducted the first HIV drug resistance (HIVDR) threshold survey in 2005, which did not identify any mutations associated with HIVDR. The objective of this study was to conduct a follow-up threshold survey to update the information on HIVDR. This study was conducted in 2009 in five antenatal care sites in Kwazulu-Natal using the HIVDR threshold survey method developed by WHO. Two hundred and thirteen newly-diagnosed HIV positive, drug-naļve primigravidae, less than 22 years of age were included in the survey. Of the 82 HIV positive specimens, 17 had insufficient volume for genotyping and, of the remaining 65, 47 were genotyped sequentially. Drug resistance was identified by sequencing the HIV-1 pol gene, using the ViroSeq® HIV-1 genotyping system v2.0. Of the 47 samples that were genotyped, only one presented with a K103N mutation, which equates to a prevalence of transmitted HIVDR of <5%. The low prevalence of transmitted HIVDR is in keeping with statistical models of the early stages of ART rollout. As ART coverage is increasing continuously, there is a need to ensure that vigilance of HIVDR continues so that the emergence and spread of HIVDR is minimized. PMID:21739439

  13. Psychosocial and demographic correlates of drug use in a sample of HIV-positive adults ages 50 and older.

    PubMed

    Siconolfi, Daniel E; Halkitis, Perry N; Barton, Staci C; Kingdon, Molly J; Perez-Figueroa, Rafael E; Arias-Martinez, Vanessa; Karpiak, Stephen; Brennan-Ing, Mark

    2013-12-01

    The prevalence of HIV among adults 50 and older in the USA is increasing as a result of improvements in treatment and detection of HIV infection. Substance use by this population has implications for physical and mental health outcomes. We examined patterns of demographics, mental health, and recent substance use in a diverse sample of heterosexual, bisexual, and gay adults 50 and older living with HIV/AIDS (PLWHA) in New York City. The most commonly used substances were cigarettes or alcohol; however, the majority of the sample did not report recent use of marijuana, poppers, or hard drugs (crystal methamphetamine, cocaine, crack, heroin, ecstasy, GHB, ketamine, and LSD or PCP). Statistically significant associations between substance use and psychological states (well-being and loneliness) were generally weak, and depression scores were not significantly related to use; instead, drug use was associated with gender/sexual orientation. The study observations support addressing substance use specific to subpopulations within PLWHA. PMID:23408281

  14. Can clinical pharmacy services have a positive impact on drug-related problems and health outcomes in community-based older adults?

    Microsoft Academic Search

    Joseph T Hanlon; Catherine I Lindblad; Shelly L Gray

    2004-01-01

    Background: Although pharmacotherapy can be beneficial in the elderly, it can also lead to drug-related problems (DRPs), including untreated indications, drug use without an indication, improper drug selection, subtherapeutic dosage, overdosage, medication error, medication nonadherence, drug interactions, adverse drug reactions, adverse drug withdrawal events, and therapeutic failure.Objective: The goal of this article was to review evidence from randomized controlled studies

  15. Adherence to antiretroviral drug therapy in adult patients who are HIV-positive in Northwest Ethiopia: a study protocol

    PubMed Central

    Bezabhe, Woldesellassie M; Peterson, Gregory M; Bereznicki, Luke; Chalmers, Leanne; Gee, Peter

    2013-01-01

    Introduction Achievement of optimal medication adherence and management of antiretroviral toxicity pose great challenges among Ethiopian patients with HIV/AIDS. There is currently a lack of long-term follow-up studies that identify the barriers to, and facilitators of, adherence to antiretroviral therapy (ART) in the Ethiopian setting. Therefore, we aim to investigate the level of adherence to ART and a wide range of potential influencing factors, including adverse drug reactions occurring with ART. Methods and analysis We are conducting a 1-year prospective cohort study involving adult patients with HIV/AIDS starting on ART between December 2012 and March 2013. Data are being collected on patients’ appointment dates in the ART clinics. Adherence to ART is being measured using pill count, medication possession ratio and patient's self-report. The primary outcome of the study will be the proportion of patients who are adherent to their ART regimen at 3, 6 and 12?months using pill count. Taking 95% or more of the dispensed ART regimen using pill count at given points of time will be considered the optimal level of adherence in this study. Data will be analysed using descriptive and inferential statistical procedures. Ethics and dissemination Ethics approval was obtained from the Tasmania Health and Medical Human Research Ethics Committee and Bahir-Dar University's Ethics Committee. The results of the study will be reported in peer-reviewed scientific journals, conferences and seminar presentations. PMID:24176794

  16. drug discovery drug discovery

    E-print Network

    drug discovery at Purdue #12;drug discovery 2 #12;drug discovery 3 Introduction The drug discovery and innovative drug candidates to treat chronic and acute illnesses. Our researchers also continue to be invested in various approaches to drug discovery, which include understanding of drug targets for future drug

  17. 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

  18. Ebola Treatment Shows Promise in Monkey Study

    MedlinePLUS

    Ebola Treatment Shows Promise in Monkey Study Antiviral drug cured animals with advanced infections, researchers say To ... HealthDay News) -- An experimental drug being tested on Ebola victims in Sierra Leone has proven effective in ...

  19. First-line anti-tubercular drug resistance of mycobacterial strains from re-treatment cases that were smear-positive at 4th month onwards under the Revised National Tuberculosis Control Program

    PubMed Central

    Lahiri, Surajit; Mukherjee, Abhijit; Hazra, Supabitra; Jana, Pulak; Roy, Sandip; Saha, Brojo Kishore

    2015-01-01

    Background: Programmatic management of drug-resistant TB (PMDT) under the RNTCP is being implemented in West Bengal in a phased manner since 2011. During the initial years MDR-TB cases were identified based on criteria A. This study examines the first line anti-tubercular drug resistance pattern of mycobacteria cultured from sputum samples of MDR suspects who were retreatment cases smear positive from 4th month onwards. Materials and Methods: In the following retrospective record based study, data on Drug Sensitivity Testing (DST) of sputum samples of MDR suspects between September 2011 and August 2012 were collected from the IRL Kolkata and analysed. Sputum samples, collected in the districts maintaining adequate aseptic containment measures, were decontaminated and centrifuged and the sediment inoculated on LJ medium. Probable M. tuberculosis colonies were identified by typical colony characteristics and Ziehl-Neelsen (ZN) staining. Sensitivity of the four 1st line drugs (Streptomycin, Isoniazid, Ethambutol and Rifampicin) was deduced by the economic variant of the proportion method. Results: Of all the 917 MDR suspects whose sputum was examined, 64 mycobacteria culture positive strains (6.98%) were mono-resistant to any of the four first line anti-tubercular drugs. Among the mono-resistant strains 43 (4.69%) were resistant to Rifampicin while 12 (1.31%) were resistant to INH. There were a total 78 (8.51%) poly drug-resistant strains. MDR-TB strains were seen in 741 (80.81%) samples. Conclusion: The magnitude of drug resistance were very high among retreatment patients that were smear positive from 4th months onwards probably because of repeated courses of anti-tubercular drugs prior to drug sensitivity testing (DST). The decision of the PMDT to enlist all retreatment patients as MDR suspects at initiation will result in early identification and treatment of MDR-TB patients. PMID:25814796

  20. t-Darpp Promotes Enhanced EGFR Activation and New Drug Synergies in Her2-Positive Breast Cancer Cells

    PubMed Central

    Denny, Erin C.; Kane, Susan E.

    2015-01-01

    Trastuzumab has led to improved survival rates of HER2+ breast cancer patients. However, acquired resistance remains a problem in the majority of cases. t-Darpp is over-expressed in trastuzumab-resistant cell lines and its over-expression is sufficient for conferring the resistance phenotype. Although its mechanism of action is unknown, t-Darpp has been shown to increase cellular proliferation and inhibit apoptosis. We have reported that trastuzumab-resistant BT.HerR cells that over-express endogenous t-Darpp are sensitized to EGFR inhibition in the presence (but not the absence) of trastuzumab. The purpose of the current study was to determine if t-Darpp might modulate sensitivity to EGFR inhibitors in trastuzumab-resistant cells. Using EGFR tyrosine kinase inhibitors AG1478, gefitinib and erlotinib, we found that trastuzumab-resistant SK.HerR cells were sensitized to EGFR inhibition, compared to SK-Br-3 controls, even in the absence of trastuzumab. t-Darpp knock-down in SK.HerR cells reversed their sensitivity to EGFR inhibition. Increased EGFR sensitivity was also noted in SK.tDp cells that stably over-express t-Darpp. High levels of synergy between trastuzumab and the EGFR inhibitors were observed in all cell lines with high t-Darpp expression. These cells also demonstrated more robust activation of EGFR signaling and showed greater EGFR stability than parental cells. The T75A phosphorylation mutant of t-Darpp did not confer sensitivity to EGFR inhibition nor activation of EGFR signaling. The over-expression of t-Darpp might facilitate enhanced EGFR signaling as part of the trastuzumab resistance phenotype. This study suggests that the presence of t-Darpp in HER2+ cancers might predict the enhanced response to dual HER2/EGFR targeting. PMID:26121470

  1. Surveillance of transmitted HIV type 1 drug resistance among HIV type 1-positive women attending an antenatal clinic in Kakinada, India.

    PubMed

    Thorat, Smita R; Chaturbhuj, Devidas N; Hingankar, Nitin K; Chandrasekhar, Velura; Koppada, Rajasekhar; Datkar, Sharda R; Srikantiah, Padmini; Garg, Renu; Kabra, Sandhya; Haldar, Partha; Reddy, Dandu C S; Bachani, Damodar; Tripathy, Srikanth P; Paranjape, Ramesh S

    2011-12-01

    The World Health Organizations HIV Drug Resistance (WHO HIVDR) Threshold survey method was used to assess transmitted HIVDR in newly diagnosed HIV-1-infected primigravida women attending the Prevention of Parent to Child Transmission (PPTCT) centers in Kakinada, in whom it is likely that the infection had recently occurred. Out of the 56 consecutively collected eligible specimens, 51 were tested using the ViroSeq RT-PCR method (Abbott Germany) to obtain 47 consecutive sequences for the HIV-1 protease (PR) and reverse transcriptase (RT) region. As per the 2009 WHO list of mutations for surveillance of transmitted HIVDR, only one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation was detected at K101E from all specimens tested, suggesting a low prevalence (<5%) of resistance to NNRTIs and no mutations were detected at other sites, suggesting a low prevalence (<5%) of resistance to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) drug classes as well. Phylogenetic analysis showed all sequences belonged to HIV-1 subtype C. In the wake of antiretroviral treatment (ART) scale-up, future evaluation of transmitted HIVDR is essential in Kakinada as well as in other regions of India. PMID:21568760

  2. Crystal structure of peptidyl-tRNA hydrolase from a Gram-positive bacterium, Streptococcus pyogenes at 2.19 Å resolution shows the closed structure of the substrate-binding cleft

    PubMed Central

    Singh, Avinash; Gautam, Lovely; Sinha, Mau; Bhushan, Asha; Kaur, Punit; Sharma, Sujata; Singh, T.P.

    2014-01-01

    Peptidyl-tRNA hydrolase (Pth) catalyses the release of tRNA and peptide components from peptidyl-tRNA molecules. Pth from a Gram-positive bacterium Streptococcus pyogenes (SpPth) was cloned, expressed, purified and crystallised. Three-dimensional structure of SpPth was determined by X-ray crystallography at 2.19 Å resolution. Structure determination showed that the asymmetric unit of the unit cell contained two crystallographically independent molecules, designated A and B. The superimposition of C? traces of molecules A and B showed an r.m.s. shift of 0.4 Å, indicating that the structures of two crystallographically independent molecules were identical. The polypeptide chain of SpPth adopted an overall ?/? conformation. The substrate-binding cleft in SpPth is formed with three loops: the gate loop, Ile91–Leu102; the base loop, Gly108–Gly115; and the lid loop, Gly136–Gly150. Unlike in the structures of Pth from Gram-negative bacteria, the entry to the cleft in the structure of SpPth appeared to be virtually closed. However, the conformations of the active site residues were found to be similar. PMID:25389518

  3. 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

  4. Drug interactions with antiviral drugs.

    PubMed

    Taburet, A M; Singlas, E

    1996-05-01

    Antiviral drug interactions are a particular problem among immuno-compromised patients because these patients are often receiving multiple different drugs, i.e. antiretroviral drugs and drugs effective against herpesvirus. The combination of zidovudine and other antiretroviral drugs with different adverse event profiles, such as didanosine, zalcitabine and lamivudine, appears to be well tolerated and no relevant pharmacokinetic interactions have been detected. The adverse effects of didanosine and zalcitabine (i.e. peripheral neuropathy and pancreatitis) should be taken into account when administering these drugs with other drugs with the same tolerability profile. Coadministration of zidovudine and ganciclovir should be avoided because of the high rate of haematological intolerance. In contrast, zidovudine and foscarnet have synergistic effect and no pharmacokinetic interaction has been detected. No major change in zidovudine pharmacokinetics was seen when the drug was combined with aciclovir, famciclovir or interferons. However, concomitant use of zidovudine and ribavirin is not advised. Although no pharmacokinetic interaction was documented when didanosine was first administered with intravenous ganciclovir, recent studies have shown that concentration of didanosine are increased by 50% or more when coadministered with intravenous or oral ganciclovir. The mechanism of this interaction has not been elucidated. Lack of pharmacokinetic interaction was demonstrated between foscarnet and didanosine or ganciclovir. Clinical trials have shown that zidovudine can be administered safely with paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, oxazepam or codeine. Inhibition of zidovudine glucuronidation has been demonstrated with fluconazole, atovaquone, valproic acid (valproate sodium), methadone, probenecid and inosine pranobex; however, the clinical consequences of this have not been fully investigated. No interaction has been demonstrated with didanosine per se but care should be taken of interaction with the high pH buffer included in the tablet formulation. Drugs that need an acidic pH for absorption (ketoconazole, itraconazole but not fluconazole, dapsone, pyrimethamine) or those that can be chelated by the ions of the buffer (quinolones and tetracyclines) should be administered 2 hours before or 6 hours after didanosine. Very few interaction studies have been undertaken with other antiviral drugs. Coadministration of zalcitabine with the antacid 'Maalox' results in a reduction of its absorption. Dapsone does not influence the disposition of zalcitabine. Cotrimoxazole (trimethoprim-sulfamethoxazole) causes an increase in lamivudine concentrations by 43%. Saquinavir, delavirdine and atevirdine appeared to be metabolised by cytochrome P450 and interactions with enzyme inducers or inhibitors could be anticipated. Some studies showed that interferons can reduce drug metabolism but only a few studies have evaluated the pathways involved. Further studies are required to better understand the clinical consequences of drug interactions with antiviral drugs. Drug-drug interactions should be considered in addition to individual drug clinical benefits and safety profiles. PMID:8743337

  5. Evaluation of an Automated Rapid Diagnostic Assay for Detection of Gram-Negative Bacteria and Their Drug-Resistance Genes in Positive Blood Cultures

    PubMed Central

    Tojo, Masayoshi; Fujita, Takahiro; Ainoda, Yusuke; Nagamatsu, Maki; Hayakawa, Kayoko; Mezaki, Kazuhisa; Sakurai, Aki; Masui, Yoshinori; Yazaki, Hirohisa; Takahashi, Hiroshi; Miyoshi-Akiyama, Tohru; Totsuka, Kyoichi; Kirikae, Teruo; Ohmagari, Norio

    2014-01-01

    We evaluated the performance of the Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN; Nanosphere, Northbrook, IL, USA), an automated multiplex assay for rapid identification of positive blood cultures caused by 9 Gram-negative bacteria (GNB) and for detection of 9 genes associated with ?-lactam resistance. The BC-GN assay can be performed directly from positive blood cultures with 5 minutes of hands-on and 2 hours of run time per sample. A total of 397 GNB positive blood cultures were analyzed using the BC-GN assay. Of the 397 samples, 295 were simulated samples prepared by inoculating GNB into blood culture bottles, and the remaining were clinical samples from 102 patients with positive blood cultures. Aliquots of the positive blood cultures were tested by the BC-GN assay. The results of bacterial identification between the BC-GN assay and standard laboratory methods were as follows: Acinetobacter spp. (39 isolates for the BC-GN assay/39 for the standard methods), Citrobacter spp. (7/7), Escherichia coli (87/87), Klebsiella oxytoca (13/13), and Proteus spp. (11/11); Enterobacter spp. (29/30); Klebsiella pneumoniae (62/72); Pseudomonas aeruginosa (124/125); and Serratia marcescens (18/21); respectively. From the 102 clinical samples, 104 bacterial species were identified with the BC-GN assay, whereas 110 were identified with the standard methods. The BC-GN assay also detected all ?-lactam resistance genes tested (233 genes), including 54 blaCTX-M, 119 blaIMP, 8 blaKPC, 16 blaNDM, 24 blaOXA-23, 1 blaOXA-24/40, 1 blaOXA-48, 4 blaOXA-58, and 6 blaVIM. The data shows that the BC-GN assay provides rapid detection of GNB and ?-lactam resistance genes in positive blood cultures and has the potential to contributing to optimal patient management by earlier detection of major antimicrobial resistance genes. PMID:24705449

  6. Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial

    PubMed Central

    Jiang, Yan; Zhang, Zhen-Lin; Zhang, Zhong-Lan; Zhu, Han-Min; Wu, Yi-Yong; Cheng, Qun; Wu, Feng-Li; Xing, Xiao-Ping; Liu, Jian-Li; Yu, Wei; Meng, Xun-Wu

    2014-01-01

    Objective To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. Method This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 ?g/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. Results A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. Conclusion Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women. PMID:24426779

  7. Swedish high-school pupils’ attitudes towards drugs in relation to drug usage, impulsiveness and other risk factors

    PubMed Central

    Jimmefors, Alexander; Archer, Trevor; Ewalds-Kvist, Béatrice

    2014-01-01

    Background. Illicit drug use influences people’s lives and elicits unwanted behaviour. Current research shows that there is an increase in young people’s drug use in Sweden. The aim was to investigate Swedish high-school pupils’ attitudes, impulsiveness and gender differences linked to drug use. Risk and protective factors relative to drug use were also a focus of interest. Method. High school pupils (n = 146) aged 17–21 years, responded to the Adolescent Health and Development Inventory, Barratt Impulsiveness Scale and Knowledge, and the Attitudes and Beliefs. Direct logistic, multiple regression analyses, and Multivariate Analysis of Variance were used to analyze the data. Results. Positive Attitudes towards drugs were predicted by risk factors (odds ratio = 37.31) and gender (odds ratio = .32). Risk factors (odds ratio = 46.89), positive attitudes towards drugs (odds ratio = 4.63), and impulsiveness (odds ratio = 1.11) predicted drug usage. Risk factors dimensions Family, Friends and Individual Characteristic were positively related to impulsiveness among drug users. Moreover, although boys reported using drugs to a greater extent, girls expressed more positive attitude towards drugs and even reported more impulsiveness than boys. Conclusion. This study reinforces the notion that research ought to focus on gender differences relative to pro-drug attitudes along with testing for differences in the predictors of girls’ and boys’ delinquency and impulsiveness. Positive attitudes towards drugs among adolescents seem to be part of a vicious circle including risk factors, such as friendly drug environments (e.g., friends who use drugs) and unsupportive family environments, individual characteristics, and impulsiveness. PMID:24949233

  8. Swedish high-school pupils' attitudes towards drugs in relation to drug usage, impulsiveness and other risk factors.

    PubMed

    Mousavi, Fariba; Garcia, Danilo; Jimmefors, Alexander; Archer, Trevor; Ewalds-Kvist, Béatrice

    2014-01-01

    Background. Illicit drug use influences people's lives and elicits unwanted behaviour. Current research shows that there is an increase in young people's drug use in Sweden. The aim was to investigate Swedish high-school pupils' attitudes, impulsiveness and gender differences linked to drug use. Risk and protective factors relative to drug use were also a focus of interest. Method. High school pupils (n = 146) aged 17-21 years, responded to the Adolescent Health and Development Inventory, Barratt Impulsiveness Scale and Knowledge, and the Attitudes and Beliefs. Direct logistic, multiple regression analyses, and Multivariate Analysis of Variance were used to analyze the data. Results. Positive Attitudes towards drugs were predicted by risk factors (odds ratio = 37.31) and gender (odds ratio = .32). Risk factors (odds ratio = 46.89), positive attitudes towards drugs (odds ratio = 4.63), and impulsiveness (odds ratio = 1.11) predicted drug usage. Risk factors dimensions Family, Friends and Individual Characteristic were positively related to impulsiveness among drug users. Moreover, although boys reported using drugs to a greater extent, girls expressed more positive attitude towards drugs and even reported more impulsiveness than boys. Conclusion. This study reinforces the notion that research ought to focus on gender differences relative to pro-drug attitudes along with testing for differences in the predictors of girls' and boys' delinquency and impulsiveness. Positive attitudes towards drugs among adolescents seem to be part of a vicious circle including risk factors, such as friendly drug environments (e.g., friends who use drugs) and unsupportive family environments, individual characteristics, and impulsiveness. PMID:24949233

  9. A Combined Analysis of 48 Type 2 Diabetes Genetic Risk Variants Shows No Discriminative Value to Predict Time to First Prescription of a Glucose Lowering Drug in Danish Patients with Screen Detected Type 2 Diabetes

    PubMed Central

    Hornbak, Malene; Allin, Kristine Hųjgaard; Jensen, Majken Linnemann; Lau, Cathrine Juel; Witte, Daniel; Jųrgensen, Marit Eika; Sandbęk, Annelli; Lauritzen, Torsten; Andersson, Åsa; Pedersen, Oluf; Hansen, Torben

    2014-01-01

    Objective To investigate the genetic influence of 48 type 2 diabetes susceptibility variants on disease progression measured as risk of early prescription redemption of glucose lowering drugs in screen-detected patients with type 2 diabetes. Methods We studied type 2 diabetes progression in 1,480 patients with screen-detected type 2 diabetes from the ADDITION-Denmark study using information of redeemed prescriptions from the Register of Medicinal Products Statistics from 2001–2009 in Denmark. Patients were cluster randomized by general practitioners, who were randomized to treat type 2 diabetes according to either a conventional or a multifactorial intensive treatment algorithm. We investigated the genetic influence on diabetes progression by constructing a genetic risk score (GRS) of all 48 validated type 2 diabetes susceptibility variants, a GRS of 11 variants linked to ?-cell function and a GRS of 3 variants linked to insulin sensitivity and assessed the association between number of risk alleles and time from diagnosis until first redeemed prescription of either any glucose lowering drug or an insulin drug. Results The GRS linked to insulin sensitivity only nominally increased the risk of an early prescription redemption with an insulin drug by 39% (HR [95% C.I.]?=?1.39 [1.09–1.77], p?=?0.009] in patients randomized to the intensive treatment group. Furthermore, the strongest univariate predictors of diabetes progression for the intensive treatment group (measured as time to first insulin) were younger age (HR [95% C.I.]?=?0.96 [0.93–0.99]), increased BMI (1.05 [1.01–1.09]), increased HbA1c (1.50 [1.36–.66]), increased TG (1.24 [1.11–1.39]) and reduced fasting serum HDL (0.37 [0.17–0.80]) at baseline. Similar results were obtained for the conventional treatment group. Conclusion Higher levels of HbA1c, fasting circulating levels of triglyceride, lower HDL, larger BMI and younger age are significant determinants of early pharmacological intervention in type 2 diabetes. However, known common type 2 diabetes-associated gene variants do not appear to significantly affect disease progression. PMID:25157406

  10. 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 cognitive measures in their precision and power to track disease progression, greatly reducing sample size estimates for drug trials. In the largest TBM study to date, we studied how sample size estimates

  11. Random Drug Tests at Work

    Microsoft Academic Search

    Robert L DuPont; David W. Griffin; Bernard R. Siskin; Sarah Shiraki; Edward Katz

    1995-01-01

    Random drug testing in the workplace has become more common since federal guidelines were issued in 1988, despite the criticism that most positive tests are the result of occasional use of illicit drugs. In order to determine the relative probabilities of detecting frequent versus infrequent users of illicit drugs, a survey of 15 experts in the drug abuse field was

  12. Heavy injection drug use is associated with lower percent body fat in a multi-ethnic cohort of HIV-positive and HIV-negative drug users from three U.S. cities

    PubMed Central

    Tang, Alice M.; Forrester, Janet E.; Spiegelman, Donna; Flanigan, Timothy; Dobs, Adrian; Skinner, Sally; Wanke, Christine

    2010-01-01

    Background The clinical implications of lower body weight in drug using populations are uncertain given that lower mean weights may still fall within the healthy range. Objectives To determine the effect of type, mode and frequency of drug use on underlying body composition after accounting for differences in body shape and size. Methods We conducted a cross-sectional analysis of 511 participants from the Tufts Nutrition Collaborative (TNC) Study. Data included measures of body composition, a 24-hour dietary recall, and a detailed health history and lifestyle questionnaire. Multivariate regression analysis was used to determine the independent effect of drug use on percent body fat (BF) after adjusting for BMI and waist circumference. Results Heavy injection drug users (IDUs) had a 2.6% lower percent BF than non-users after adjusting for BMI, waist circumference, and other confounders. (p=0.0006). Differences in percent BF were predominantly due to higher lean mass, rather than lower fat mass. Cocaine and heroin had similar effects on body composition. Conclusions In the U.S., where the general population is prone to over-nutrition, the average percent BF for heavy injectors does not fall into a range low enough to suggest harmful effects. However, in populations with substantial levels of under-nutrition, small differences in percent BF among drug users will have a greater impact on health status. Scientific Significance Differences in BMI, weight and body composition are not always straightforward. Accounting for underlying nutritional status and relative differences in fat and FFM is critical when interpreting results. PMID:20141402

  13. Oral Fluid Testing for Drugs of Abuse: Positive Prevalence Rates by Intercept™ Immunoassay Screening and GC-MS-MS Confirmation and Suggested Cutoff Concentrations

    Microsoft Academic Search

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

    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

  14. Association of Alcohol Abuse and Injection Drug Use with Immunologic and Virologic Responses to HAART in HIV-positive Patients from Urban Community Health Clinics

    Microsoft Academic Search

    Timothy J. Henrich; Naudia Lauder; Mayur M. Desai; Andre N. Sofair

    2008-01-01

    The purpose of this study is to examine the association of alcohol abuse and injection drug use (IDU) with the immunologic\\u000a and virologic responses to highly active antiretroviral treatment (HAART) in urban community health clinics. The medical records\\u000a of 293 HIV-infected adult patients who visited either of two urban health clinics in New Haven, Connecticut, from June 2003\\u000a to December

  15. 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

  16. Effect of zinc and vitamin A supplementation on antibody responses to a pneumococcal conjugate vaccine in HIV-positive injection drug users: a randomized trial.

    PubMed

    Deloria-Knoll, Maria; Steinhoff, Mark; Semba, Richard D; Nelson, Kenrad; Vlahov, David; Meinert, Curtis L

    2006-03-01

    HIV-infected individuals have impaired immune responses to vaccines and high rates of pneumococcal disease. The effect of vitamin A and zinc supplementation on the immunogenicity of a 7-valent pneumococcal CRM-197 conjugate vaccine (PC-7) was evaluated in 118 HIV+ injection drug users. Subjects were randomized to oral 400,000 IU vitamin A, 300 mg zinc, vitamin A + zinc, or placebo, then immunized. Geometric mean titer increased 1.3-3.3-fold for all pneumococcal serotypes. PC-7 elicited an immune response in HIV-infected adults but neither vitamin A nor zinc altered the immunogenicity of the evaluated vaccines. PMID:16256250

  17. Taking drugs very seriously.

    PubMed

    Corlett, J Angelo

    2013-04-01

    Neither anti-illegal drug proponents nor their detractors have wholly plausible arguments for their positions, because neither takes responsibility for drug use sufficiently seriously. Instead, only a policy that places users' responsibility at the forefront of the problem is acceptable, one that is sufficiently respectful of actual or potential nonusers' rights not to be wrongfully harmed, directly or indirectly, by drug use, or coerced to support it in any way. PMID:23449363

  18. Drug Safety

    MedlinePLUS

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

  19. 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 ...

  20. Drugs, Alcohol and HIV

    MedlinePLUS

    ... Keep in mind that recreational drugs aren't regulated, so you never know exactly how much you ... HIV positive (AIDSmap). The Drinkers Check-up A self-evaluation tool for people who drink alcohol and ...

  1. Autumn shows roundup

    Microsoft Academic Search

    Richard Bloss

    2002-01-01

    A report on three major American automation shows where innovative products and automated assembly technologies formed a focus. Products reviewed include grippers, actuators, assembly modules, dispensing controller and pneumatic components from a number of suppliers.

  2. Do Elephants Show Empathy?

    Microsoft Academic Search

    Lucy A. Bates; Phyllis C. Lee; Norah Njiraini; Joyce H. Poole; Katito Sayialel; Soila Sayialel; Cynthia J. Moss; Richard W. Byrne

    2008-01-01

    Elephants show a rich social organization and display a number of unusual traits. In this paper, we analyse reports collected over a thirty-five year period, describing behaviour that has the potential to reveal signs of empathic understanding. These include coalition formation, the offering of protection and comfort to others, retrieving and 'babysitting' calves, aiding individuals that would otherwise have difficulty

  3. 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…

  4. Demonstration Road Show

    NSDL National Science Digital Library

    2009-04-06

    The Idaho State University Department of Physics conducts science demonstration shows at S. E. Idaho schools. Four different presentations are currently available; "Forces and Motion", "States of Matter", "Electricity and Magnetism", and "Sound and Waves". Information provided includes descriptions of the material and links to other resources.

  5. Earthquake Damage Slide Show

    NSDL National Science Digital Library

    This slide show presents examples of various types of damage caused by earthquakes. Photos include structural failures in bridges and buildings, landshifts, landslides, liquefaction, fires, tsunamis, and human impacts. Supplemental notes are provided to aid instructors about the photos presented on each slide.

  6. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  7. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  8. Drugs, drugs--who has the drugs?

    PubMed

    Blair, James

    2012-01-01

    Drug diversion, although on the increase, is not the only problem involving drugs that hospital security officials should be concerned with. Growing drug shortages, offshore production, counterfeiting, and weaknesses in the drug supply chain in case of a world-wide pandemic, are even greater causes for concern, the author claims. PMID:22423518

  9. The drug cocktail network

    PubMed Central

    2012-01-01

    Background Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations. Results In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (Drug Combination Predictor) to predict possible drug combinations by exploiting the topological features of the drug cocktail network. Validating on the known drug combinations, DCPred achieves the overall AUC (Area Under the receiver operating characteristic Curve) score of 0.92, indicating the predictive power of our proposed approach. Conclusions The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations. PMID:23046711

  10. 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…

  11. Redefining America's "War on Drugs"

    E-print Network

    McQuade, D. Tyler

    Redefining America's "War on Drugs" FSU Center for the Advancement of Human Rights presents Office of National Drug Control Policy (ONDCP) Director Kerlikowske was nominated by President Obama and confirmed by the U.S. Senate as the Director of the Office of National Drug Control Policy. In his position

  12. Show-Me Center

    NSDL National Science Digital Library

    The Show-Me Center is a partnership of four NSF-sponsored middle grades mathematics curriculum development Satellite Centers (University of Wisconsin, Michigan State University, University of Montana, and the Educational Development Center). The group's website provides "information and resources needed to support selection and implementation of standards-based middle grades mathematics curricula." The Video Showcase includes segments on Number, Algebra, Geometry, Measure, and Data Analysis, with information on ways to obtain the complete video set. The Curricula Showcase provides general information, unit goals, sample lessons and teacher pages spanning four projects: the Connected Mathematics Project (CMP), Mathematics in Context (MiC), MathScape: Seeing and Thinking Mathematically, and Middle Grades Math Thematics. The website also posts Show-Me Center newsletters, information on upcoming conferences and workshops, and links to resources including published articles and unpublished commentary on mathematics school reform.

  13. The Truman Show

    Microsoft Academic Search

    Rolf F. Nohr

    The Truman Show is hardly a film you would automatically speak about as a game. At first glance, it is tempting to interpret the story of\\u000a Truman Burbank — his perpetual subjection to the artificial (televisual) world of Seahaven and its gargantuan reality TV project,\\u000a his eventual escape from the “OmniCam Ecosphere” building and the paternalistic surveillance of director Christof

  14. 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

  15. 76 FR 18072 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ...Procedures for Transportation Workplace Drug and Alcohol Testing Programs CFR Correction In...2) * * * (i) Positive, with drug(s)/metabolite(s) noted, with numerical values for the drug(s) or drug...

  16. 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.

  17. 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

  18. 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

  19. Nasal Carriage of Multi-Drug Resistant Panton-Valentine Leucocidin-Positive Methicillin-Resistant Staphylococcus aureus in Children in Tripoli-Libya

    PubMed Central

    Al-haddad, Omaima H.; Zorgani, Abdulaziz; Sifaw Ghenghesh, Khalifa

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonized children are at an increased risk of developing infections than methicillin-sensitive S. aureus colonized children. Nasal specimens from inpatient children, mothers of inpatient children, healthcare workers, and outpatient children at Tripoli Children Hospital (TCH) were examined for MRSA by chromogenic MRSA ID medium. Susceptibility of MRSA isolates to antibiotics was determined by the disc diffusion method. The nasal carriage rate of MRSA among inpatient children (8.3%, 24 of 289), their mothers (11%, 22 of 200), and healthcare workers (12.4%, 22 of 178) was significantly higher than among outpatient children (2.2%, 2 of 91) (P < 0.05, P < 0.02, and P < 0.006, respectively). Of the examined MRSA isolates (N = 35) 10 (28.6%) were positive for Panton-Valentine leucocidin genes by polymerase chain reaction. Multidrug resistance was found in 24.3% (17 of 70) of MRSA isolates. Nasal carriage of multidrug-resistant Panton-Valentine leucocidin-positive MRSA is not uncommon among inpatient children and their mothers in Tripoli. PMID:24493673

  20. American History Picture Show

    NSDL National Science Digital Library

    Ms. Bennion

    2009-11-23

    In class we read Katie's Picture Show, a book about a girl who discovers art first-hand one day at an art museum in London. She realizes she can climb into the paintings, explore her surroundings, and even solve problems for the subjects of the paintings. As part of our unit on American history, we are going to use art to further learn about some of the important events we have been discussing. Each of these works of art depicts an important event in American History. When you click on a picture, you will be able to see the name of the event as well as the artist who created it. You will be using all three pictures for this assignment.Use the websites ...

  1. Club Drugs

    MedlinePLUS

    Club drugs are group of psychoactive drugs. They act on the central nervous system and can cause changes ... Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap ...

  2. Drug Resistance

    MedlinePLUS

    ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ... does poor medication adherence increase the risk of drug resistance? Medication adherence means taking HIV medicines every ...

  3. 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 ...

  4. Frequency of Positive Studies Among Fixed and Flexible Dose Antidepressant Clinical Trials: An Analysis of the Food and Drug Administraton Summary Basis of Approval Reports

    Microsoft Academic Search

    Arif Khan; Shirin R Khan; Gary Walens; Russell Kolts; Earl L Giller

    2003-01-01

    The assumption that the design of an antidepressant clinical trial affects the outcome of that trial is based on sparse data. We sought to examine if the dosing schedule, either a fixed dose or a flexible dose type, in an antidepressant clinical trial affects the frequency with which antidepressants show statistical superiority over placebo. Randomized, placebo-controlled clinical trials of nine

  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. 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...

  7. Drug–drug interaction through molecular structure similarity analysis

    PubMed Central

    Harpaz, Rave; Uriarte, Eugenio; Santana, Lourdes; Rabadan, Raul; Friedman, Carol

    2012-01-01

    Background Drug–drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs. Methods We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. DrugBank was used as a resource for collecting 9454 established DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to identify DDI candidates. Results The methodology was evaluated using as a gold standard the interactions retrieved from the initial DrugBank database. Results demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision of 0.26. Additionally, the methodology was also evaluated in an independent test using the Micromedex/Drugdex database. Conclusion The proposed methodology is simple, efficient, allows the investigation of large numbers of drugs, and helps highlight the etiology of DDI. A database of 58?403 predicted DDIs with structural evidence is provided as an open resource for investigators seeking to analyze DDIs. PMID:22647690

  8. Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function

    PubMed Central

    Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

    2014-01-01

    In this paper, we present a magnetically actuated multimodal drug release mechanism using a tetherless soft capsule endoscope for the treatment of gastric disease. Because the designed capsule has a drug chamber between both magnetic heads, if it is compressed by the external magnetic field, the capsule could release a drug in a specific position locally. The capsule is designed to release a drug in two modes according to the situation. In the first mode, a small amount of drug is continuously released by a series of pulse type magnetic field (0.01–0.03 T). The experimental results show that the drug release can be controlled by the frequency of the external magnetic pulse. In the second mode, about 800 mm3 of drug is released by the external magnetic field of 0.07 T, which induces a stronger magnetic attraction than the critical force for capsule’s collapsing. As a result, a polymeric coating is formed around the capsule. The coated area is dependent on the drug viscosity. This paper presents simulations and various experiments to evaluate the magnetically actuated multimodal drug release capability. The proposed soft capsules could be used as minimally invasive tetherless medical devices with therapeutic capability for the next generation capsule endoscopy. PMID:25378896

  9. Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function.

    PubMed

    Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

    2013-01-01

    In this paper, we present a magnetically actuated multimodal drug release mechanism using a tetherless soft capsule endoscope for the treatment of gastric disease. Because the designed capsule has a drug chamber between both magnetic heads, if it is compressed by the external magnetic field, the capsule could release a drug in a specific position locally. The capsule is designed to release a drug in two modes according to the situation. In the first mode, a small amount of drug is continuously released by a series of pulse type magnetic field (0.01-0.03 T). The experimental results show that the drug release can be controlled by the frequency of the external magnetic pulse. In the second mode, about 800 mm(3) of drug is released by the external magnetic field of 0.07 T, which induces a stronger magnetic attraction than the critical force for capsule's collapsing. As a result, a polymeric coating is formed around the capsule. The coated area is dependent on the drug viscosity. This paper presents simulations and various experiments to evaluate the magnetically actuated multimodal drug release capability. The proposed soft capsules could be used as minimally invasive tetherless medical devices with therapeutic capability for the next generation capsule endoscopy. PMID:25378896

  10. 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

  11. In silico modeling to predict drug-induced phospholipidosis

    SciTech Connect

    Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov; 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.

  12. Drug-Path: a database for drug-induced pathways

    PubMed Central

    Zeng, Hui; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. Database URL: http://www.cuilab.cn/drugpath

  13. 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

  14. New View on Treatment of Drug Dependence

    PubMed Central

    Ranjbaran, Mina; Sahraei, Hedayat

    2014-01-01

    In the 1960s, discovery of pleasure system (defined as reward system) in the brain that may underlie drug reward and addiction encouraged many scientists to investigate the mechanisms by which drug abuse affects central nervous system function. In this regard, investigators developed several drugs targeting the brain reward system for drug dependence therapy. However, no positive results obtained in drug addiction treatment. It seems that more brain systems other than brain reward system must be considered in this regard. PMID:25436090

  15. Drug Cravings

    NSDL National Science Digital Library

    Science Update

    2003-07-14

    Many drug users successfully break their habit in rehab, only to resume abusing drugs once they re-enter the real world. In this Science Update, you'll hear about new research in rats that reveals why staying off drugs can be so difficult.

  16. An Outreach Program in Drug Education; Teaching a Rational Approach to Drug Use

    ERIC Educational Resources Information Center

    Sorensen, James L.; Joffe, Stephen J.

    1975-01-01

    Aimed at encouraging rational decision making about drug use, a peer oriented drug education program was conducted in a community youth project. Youth and leaders shared feelings and knowledge about drugs. Compared with four program dropouts, six participants exhibited more positive attitudes toward the drug group, its leaders and themselves.…

  17. Secondary analyses of data from four studies with fourth-grade children show that sex, race, amounts eaten of standardized portions, and energy content given in trades explain the positive relationship between BMI and energy intake at school-provided meals

    PubMed Central

    Baxter, Suzanne Domel; Paxton-Aiken, Amy E.; Tebbs, Joshua M.; Royer, Julie A.; Guinn, Caroline H.; Finney, Christopher J.

    2012-01-01

    Results from a 2012 article showed a positive relationship between children’s body mass index (BMI) and energy intake at school-provided meals. To help explain that positive relationship, secondary analyses investigated 1) whether the relationship differed by sex and race, and 2) the relationship between BMI and six aspects of school-provided meals—amounts eaten of standardized portions, energy content given in trades, energy intake received in trades, energy intake from flavored milk, energy intake from a la carte ice cream, and breakfast type. Data were from four studies conducted one per school year (1999–2000 to 2002–2003). Fourth-grade children (n=328; 50% female; 54% Black) from 13 schools total were observed eating school-provided breakfast and lunch on one to three days per child for 1,178 total meals (50% breakfast). Children were weighed and measured. Marginal regression models were fit using BMI as the dependent variable. For Purpose One, independent variables were energy intake at school-provided meals, sex, race, age, and study; additional models included interaction terms involving energy intake and sex/race. For Purpose Two, independent variables were the six aspects of school-provided meals, sex, race, age, and study. The relationship between BMI and energy intake at school-provided meals differed by sex (p<0.0001; stronger for females) and race (p=0.0063; stronger for Black children). BMI was positively related to amounts eaten of standardized portions (p<0.0001) and negatively related to energy content given in trades (p=0.0052). Explaining the positive relationship between BMI and energy intake at school-provided meals may contribute to school-based obesity prevention efforts. PMID:23084638

  18. 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

  19. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  20. 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

  1. Cheimical Dependency and Drug Testing in the Workplace

    Microsoft Academic Search

    John D. Osterloh; Charles E. Becker

    1990-01-01

    Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest of the illicit drugs being tested. Highly prevalent drugs can be reliably tested. Although it is prudent to rid the workplace of drug use, there is little

  2. In vitro validation of drug-induced phospholipidosis.

    PubMed

    Park, Sora; Choi, You-Jin; Lee, Byung-Hoon

    2012-01-01

    Intracellular accumulation of phospholipids with lamellar bodies is a hallmark of drug-induced phospholipidosis (PLD) which is caused by impaired phospholipid metabolism of the lysosome. Although it remains uncertain whether PLD is associated with the adverse effects, sponsors generally terminate the development of a candidate drug when PLD is observed in an organ. For drugs that are used without serious adverse events, there should be labels indicating that the drug can induce PLD. We conducted LipidTox and NBD-PE assays for detecting PLD to compare and validate the methods. In the case of contrary results in both assays, electron microscopy was performed to confirm the data. We selected 12 chemicals and divided them into 4 categories: P+S+, PLD and steatosis positive; P+/S-, PLD positive and steatosis negative; P-S+, PLD negative and steatosis positive; P-/S-, PLD and steatosis negative. In general, results showed very good agreement with the known information with some minor discrepancies. LipidTox assay is proven to be a very sensitive method. Considering the contrary results of acetaminophen and menadione in LipidTox and the NBD-PE assay, the combination of two methods using different phospholipids is advantageous to reduce false positives. The finding that acetaminophen was positive in LipidTos assay and increased the frequency of lamellar body implies that acetaminophen is a weak inducer of PLD. PMID:22467016

  3. Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis

    PubMed Central

    Balachandran, Ram K.

    2011-01-01

    Purpose The vitreous humor liquefies with age and readily sloshes during eye motion. The objective was to develop a computational model to determine the effect of sloshing on intravitreal drug transport for transscleral and intra-vitreal drug sources at various locations Methods A finite element model based on a telescopic implicit envelope tracking scheme was developed to model drug dispersion. Flow velocities due to saccadic oscillations were solved for and were used to simulate drug dispersion. Results Saccades induced a three-dimensional flow field that indicates intense drug dispersion in the vitreous. Model results showed that the time scale for transport decreased for the sloshing vitreous when compared to static vitreous. Macular concentrations for the sloshing vitreous were found be much higher than that for the static vitreous. For low viscosities the position of the intravitreal source did not have a big impact on drug distribution. Conclusion Model results show that care should be taken when extrapolating animal data, which are mostly done on intact vitreous, to old patients whose vitreous might be a liquid. The decrease in drug transport time scales and changes in localized concentrations should be considered when deciding on treatment modalities and dosing strategies. PMID:21258958

  4. Treatment of Drug Susceptible Pulmonary Tuberculosis

    PubMed Central

    Shin, Hong-Joon

    2015-01-01

    Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs. PMID:26175767

  5. Plan Showing Cross Bracing Under Upper Stringers, Typical Section Showing ...

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

    Plan Showing Cross Bracing Under Upper Stringers, Typical Section Showing End Framing, Plan Showing Cross Bracing Under Lower Stringers, End Elevation - Covered Bridge, Spanning Contoocook River, Hopkinton, Merrimack County, NH

  6. Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Erlei

    2011-12-01

    Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

  7. Drug Rash (Unclassified Drug Eruption) in Adults

    MedlinePLUS

    newsletter | contact Share | Drug Eruption, Unclassified Information for adults A A A Acute drug eruption with numerous red, raised lesions. Overview A drug rash (drug eruption), also known as a drug ...

  8. 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

  9. 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.

  10. Drug interactions during periodontal therapy in HIV-infected subjects.

    PubMed

    Gonēalves, L de S; Gonēalves, B M L; de Andrade, M A C; Alves, F R F; Junior, A S

    2010-07-01

    Despite the beneficial effect of the HAART, adverse reactions and drug interaction have been observed. Abnormalities in lipid and glucose metabolism make HIV-positive patients to high risk for the development of coronary heart disease and diabetes, respectively. Besides adverse reactions, drug interaction with other medication can also be observed. In fact, drug interaction may interfere in the periodontal therapy in HIV-infected individuals. For instance, fluconazole, ketoconazole, itraconazole, metronidazole, ciprofloxacin, midazolam and triazolam can interact with some antiretroviral medications, such as zidovudine, nevirapine and ritonavir. The aim of the current study was to show to periodontists and general dental practitioners the importance of understanding the drug interaction in HIV-infection in order to establish a better control during periodontal treatment. PMID:20565386

  11. Offered: Offered: Position(s): Position(s)

    E-print Network

    New Hampshire, University of

    training to introduce the basics of a career in the staffing industry -Assigned mentors to guide youCompany: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description IT staffing and Global Services for 82% of the Fortune 500. Ranked #1 in the industry by IT Services Business

  12. Offered: Offered: Position(s): Position(s)

    E-print Network

    New Hampshire, University of

    overall impact to company?s profitability ?Run monthly reports supporting Financial Analysts includingCompany: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description and creative companies making premium chocolate, with six production sites in Europe, two in the USA

  13. Roanoke Area Junior Livestock Show

    E-print Network

    Liskiewicz, Maciej

    & Computations Tom Stanley, Chairman Tyler Painter Beth Hawse Katherine Carter Ribbons & Record Keeping Carolyn Supper at Arena 6:00 PM Hog Show: Showmanship, Market Hog Show and Breeding Gilt Show 7:00 pm Check

  14. Use of genotoxicity data to support clinical trials or positive genetox findings on a candidate pharmaceutical or impurity .... now what?

    PubMed

    Jacobson-Kram, David; Jacobs, Abigail

    2005-01-01

    Results from carcinogenicity studies are generally not available for drugs until the time of approval. Many people, including healthy volunteers are often exposed to pharmacologically active doses of the drug before carcinogenicity results are available. The Food and Drug Administration (FDA) Center for Drug Evaluation and Research uses results of genetic toxicology studies as a surrogate for carcinogenicity during the drug development phase (clinical trials). A number of issues are considered in deciding whether drugs that give positive results in genetic toxicology studies can be given to subjects in clinical trials. These relate to the drug indication, the target population, duration of treatment, and importance of the drug. In general, single-dose clinical studies are permitted regardless of the genetox results. In situations where a genetic toxicology assay showed a positive result, some review divisions have asked sponsors to perform a Syrian hamster embryo (SHE) cell transformation assay or a p53 carcinogenicity study prior to allowing repeat-dose clinical trials to proceed. This paper discusses alternatives to SHE cell and p53 assays when faced with a positive result in a genetic toxicology assay. In addition, this paper discusses factors to consider when setting limits for genotoxic impurities in drug substances and products. PMID:16040563

  15. 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.

  16. 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…

  17. 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.…

  18. 6. VIEW SHOWING DOWNSTREAM FACE OF DAM, SHOWING SEEPAGE CONTROL ...

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

    6. VIEW SHOWING DOWNSTREAM FACE OF DAM, SHOWING SEEPAGE CONTROL REINFORCEMENT, LOOKING SOUTHWEST - High Mountain Dams in Upalco Unit, East Timothy Lake Dam, Ashley National Forest, 8.4 miles North of Swift Creek Campground, Mountain Home, Duchesne County, UT

  19. 10. INTERIOR VIEW SHOWING MOUNTINGS FROM TUNING DEVICE. VIEW SHOWS ...

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

    10. INTERIOR VIEW SHOWING MOUNTINGS FROM TUNING DEVICE. VIEW SHOWS COPPER SHEETING ON WALLS. - Chollas Heights Naval Radio Transmitting Facility, Helix House, 6410 Zero Road, San Diego, San Diego County, CA

  20. Street Drugs and Pregnancy

    MedlinePLUS

    ... drugs > Street drugs and pregnancy Smoking, alcohol and drugs Don’t smoke, drink alcohol or use drugs ... page It's been added to your dashboard . Street drugs and pregnancy A street drug (also called illegal ...

  1. 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).

  2. 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…

  3. Drug expenditure and new drug introductions: the Swedish experience.

    PubMed

    Gerdtham, U G; Johannesson, M; Jönsson, B

    1993-09-01

    This article measures the impact of the switch to new and more expensive drugs on the aggregate drug expenditure (both prescription and nonprescription) in Sweden during the period 1974 to 1991, and also on the disaggregated expenditure for 3 medical areas: asthma, hypertension and peptic ulcer disease. During the period studied, nominal drug expenditure increased 6-fold. The retail price index of drugs and the number of prescribed drugs accounted for 51.6 and 5.8% of this increase, respectively. The remaining residual amount accounted for 42.6%. Since the price index of drugs increased more slowly than the overall net price index of goods and services, the relative price of drugs decreased dramatically by about 30%. This means that increases in prices of drugs cannot explain the increase in real inflation-adjusted drug expenditure. We also show that the residual increase can be partly explained by the introduction of new and more expensive drugs. It is therefore argued that economic evaluations which compare the extra costs induced by new drugs with the extra benefits should be undertaken to guide decisions about the prescription of new and more expensive drugs. PMID:10146924

  4. 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

  5. In silico modeling to predict drug-induced phospholipidosis.

    PubMed

    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. PMID:23541745

  6. Polymeric complex micelles with double drug-loading strategies for folate-mediated paclitaxel delivery.

    PubMed

    Li, Min; Liu, Yongjun; Feng, Lixia; Liu, Fengxi; Zhang, Li; Zhang, Na

    2015-07-01

    Drug loading is a key procedure in the preparation of drug-loaded nano-carriers. In this study, the paclitaxel (PTX)-loaded polymeric complex micelles (FA-P123-PTX/PTX micelles) with double drug-loading strategies were designed and prepared to improve the drug loading percentage of carriers and its anti-tumor efficiency. PTX was simultaneously conjugated to pluronic P123 (P123) polymer and encapsulated inside the P123 complex micelle. Folate (FA) was linked to the surface of micelles for the active target delivery of micelles to tumor cells. The FA-P123-PTX/PTX micelles showed spherical shaped with high drug loading of 18.08±0.64%. The results of cellular uptake studies suggested that FA could promote the internalization of micelles into the FR positive cells. FA-P123-PTX/PTX micelles showed significant higher anti-tumor activity against FR positive tumor cells compared to Taxol(®) (p<0.05). Moreover, the FA-P123-PTX/PTX micelles exhibited higher anti-tumor efficacy in B16 bearing mice with better safety property compared with Taxol(®). These results suggested that FA-P123-PTX/PTX micelles with double drug-loading strategies showed great potential for targeted delivery of anti-cancer drugs. PMID:25988283

  7. What Do Blood Tests Show?

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Do Blood Tests Show? Blood tests show whether the levels ... changes may work best. Result Ranges for Common Blood Tests This section presents the result ranges for ...

  8. Asia: Showing the Changing Seasons

    NSDL National Science Digital Library

    Jesse Allen

    1998-09-09

    SeaWiFS false color data showing seasonal change in the oceans and on land for Asia. The data is seasonally averaged, and shows the sequence: fall, winter, spring, summer, fall, winter, spring (for the Northern Hemisphere).

  9. A Panton-Valentine Leucocidin (PVL)Positive Community-Acquired Methicillin-Resistant Staphylococcus aureus (MRSA) Strain, Another Such Strain Carrying a Multiple-Drug Resistance Plasmid, and Other More-Typical PVL-Negative MRSA Strains Found in Japan

    Microsoft Academic Search

    Yoko Takizawa; Ikue Taneike; Saori Nakagawa; Tomohiro Oishi; Yoshiyuki Nitahara; Nobuhiro Iwakura; Kyoko Ozaki; Misao Takano; Teruko Nakayama; Tatsuo Yamamoto

    2005-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was collected from children with bullous impetigo in 2003 and 2004. One strain collected in 2003 was Panton-Valentine leucocidin (PVL) positive. In 2004, a multiple-drug-resistant PVL CA-MRSA strain was isolated from an athlete with a cutaneous abscess. These strains were analyzed by multilocus sequence typing, spa typing, agr typing, coagulase typing, staphylococcal cassette chromosome mec

  10. Detection and prevalence of drug use in arrested drivers using the Dräger Drug Test 5000 and Affiniton DrugWipe oral fluid drug screening devices.

    PubMed

    Logan, Barry K; Mohr, Amanda L A; Talpins, Stephen K

    2014-09-01

    The use of oral fluid (OF) drug testing devices offers the ability to rapidly obtain a drug screening result at the time of a traffic stop. We describe an evaluation of two such devices, the Dräger Drug Test 5000 and the Affiniton DrugWipe, to detect drug use in a cohort of drivers arrested from an investigation of drug impaired driving (n = 92). Overall, 41% of these drivers were ultimately confirmed positive by mass spectrometry for the presence of one or more drugs. The most frequently detected drugs were cannabinoids (30%), benzodiazepines (11%) and cocaine (10%). Thirty-nine percent of drivers with blood alcohol concentrations >0.08 g/100 mL were found to be drug positive. Field test results obtained from OF samples were compared with collected OF and urine samples subsequently analyzed in the laboratory by gas or liquid chromatography-mass spectrometry. The Dräger Drug Test 5000 (DDT5000) and DrugWipe returned overall sensitivities of 51 and 53%, and positive predictive values of 93 and 63%, respectively. The most notable difference in performance was the DDT5000's better sensitivity in detecting marijuana use. Both devices failed to detect benzodiazepine use. Oral fluid proved to be a more effective confirmatory specimen, with more drugs being confirmed in OF than urine. PMID:24894458

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

    PubMed Central

    Nikoli?, Bo˛ana 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

  12. Drugged Driving

    MedlinePLUS

    ... 2014). Why is drugged driving a problem in teens and young adults? Motor vehicle crashes are the ... vehicles killed in Australian road traffic crashes. Accid Anal Prev . 2004;36(2):239-248. Hartman RL, ...

  13. Prescription Drugs

    MedlinePLUS

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  14. Drug Residues

    Microsoft Academic Search

    Philip T. Reeves

    \\u000a The use of veterinary drugs in animal production is necessary for the prevention and treatment of disease; however, such use\\u000a may result in residues. Regulatory authorities administer legislative frameworks which ensure that foods derived from animals\\u000a treated with approved veterinary drugs are safe for human consumption. A human food safety evaluation is conducted as follows:\\u000a it estimates the risk to

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

    E-print Network

    Gates, Kent. S.

    how the three analogs shown below can be prepared. Draw an arrow-pushing mechanism for each step is not active in an in vitro assay, but shows good activity in animal models and human patients. Explain: what

  16. Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle

    E-print Network

    Zhang, Liangfang

    Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle Dual-Drug Delivery Santosh Aryal, Che-Ming Jack Hu, and Liangfang Zhang* A new approach to loading multiple drugs onto the same drug through hydrolyzable linkers to form drug conjugates, is reported. In contrast to loading individual types

  17. Planning a Successful Tech Show

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2011-01-01

    Tech shows are a great way to introduce prospective students, parents, and local business and industry to a technology and engineering or career and technical education program. In addition to showcasing instructional programs, a tech show allows students to demonstrate their professionalism and skills, practice public presentations, and interact…

  18. Satellite positioning

    NASA Technical Reports Server (NTRS)

    Colombo, Oscar L.; Watkins, Michael M.

    1991-01-01

    Developments in satellite positioning techniques and their applications are reviewed on the basis of the theoretical and practical work published by U.S. researchers in 1987-1990. Current techniques are classified into two main categories: satellite laser tracking and radio tracking. Particular attention is given to the Geoscience Laser Ranging System, the Lunar Laser Ranging concept; GPS ephemerides determination, fiducial networks, and reference frame; static GPS positioning; and kinematic GPS positioning.

  19. DrugComboRanker: drug combination discovery based on target network analysis

    PubMed Central

    Huang, Lei; Li, Fuhai; Sheng, Jianting; Xia, Xiaofeng; Ma, Jinwen; Zhan, Ming; Wong, Stephen T.C.

    2014-01-01

    Motivation: Currently there are no curative anticancer drugs, and drug resistance is often acquired after drug treatment. One of the reasons is that cancers are complex diseases, regulated by multiple signaling pathways and cross talks among the pathways. It is expected that drug combinations can reduce drug resistance and improve patients’ outcomes. In clinical practice, the ideal and feasible drug combinations are combinations of existing Food and Drug Administration-approved drugs or bioactive compounds that are already used on patients or have entered clinical trials and passed safety tests. These drug combinations could directly be used on patients with less concern of toxic effects. However, there is so far no effective computational approach to search effective drug combinations from the enormous number of possibilities. Results: In this study, we propose a novel systematic computational tool DrugComboRanker to prioritize synergistic drug combinations and uncover their mechanisms of action. We first build a drug functional network based on their genomic profiles, and partition the network into numerous drug network communities by using a Bayesian non-negative matrix factorization approach. As drugs within overlapping community share common mechanisms of action, we next uncover potential targets of drugs by applying a recommendation system on drug communities. We meanwhile build disease-specific signaling networks based on patients’ genomic profiles and interactome data. We then identify drug combinations by searching drugs whose targets are enriched in the complementary signaling modules of the disease signaling network. The novel method was evaluated on lung adenocarcinoma and endocrine receptor positive breast cancer, and compared with other drug combination approaches. These case studies discovered a set of effective drug combinations top ranked in our prediction list, and mapped the drug targets on the disease signaling network to highlight the mechanisms of action of the drug combinations. Availability and implementation: The program is available on request. Contact: stwong@tmhs.org PMID:24931988

  20. Racial Differences in Graduation Rates From Adult Drug Treatment Courts

    Microsoft Academic Search

    Jerome McKean; Kiesha Warren-Gordon

    2011-01-01

    Drug courts have demonstrated promise as an intervention that is effective in reducing recidivism and thereby providing a viable alternative to incarceration for drug-involved offenders. Despite their promise, it is not clear that African Americans are as likely to have positive outcomes in drug courts as other clients. This article reviews recent research on racial differences in completion of drug

  1. 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).

  2. Recreational drugs.

    PubMed

    Iven, V G

    1998-04-01

    The war against substance abuse continues in today's society and the sports world often seems to be in the middle of all the attention, especially among the media. New recreational drugs arrive on the scene from time to time, much like GHB, but the predominant substances of abuse continue to be marijuana, cocaine, and alcohol. As research evolves in efforts to stay current and determine any potential performance effects of new substances, the literature has changed very little regarding the more common recreational drug and their effects on athletic participation. New studies are emerging comparing recreational drug use among athletes versus nonathletes. Findings include differences among these groups regarding individual sports, team sports, contact versus noncontact sports, and gender-specific sports. Higher risk-taking behavior contribute to these findings and is known to be more prevalent among an athletic population. Overall, illicit drug use in America in 1996 remained about the same as in 1995 after rising steadily since the early 1990s. About 13 million Americans used drugs at least monthly in 1996, up slightly from 12.8 million in 1995. Teenage drug and alcohol use fell to 9% in 1996, down from 10.9% in 1995. Attempts to recognize the early signs of substance abuse and identify those athletes "at risk" of experimenting with elicit drugs are paramount to the optimal treatment response program. The preparticipation examination remains the best initial format for establishing a sound physician-patient relationship. A thorough history including risk factors, family history, and personnel tendencies toward substance abuse should be obtained followed by an ongoing relationship between the athlete and his team physician. The better rapport between the athlete and team physician, the higher likelihood of early recognition of a developing substance abuse problem. Likewise, the earliest intervention usually leads to the most optimal treatment response. PMID:9580840

  3. Glioma-associated endothelial cells show evidence of replicative senescence

    SciTech Connect

    Charalambous, Christiana [Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Virrey, Jenilyn [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Kardosh, Adel [Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Jabbour, Mark N. [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Qazi-Abdullah, Lubna [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Pen, Ligaya [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Zidovetzki, Raphael [Department of Cell Biology and Neuroscience, University of California, Riverside, CA (United States); Schoenthal, Axel H. [Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Chen, Thomas C. [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA (United States); Hofman, Florence M. [Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA (United States) and Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA (United States)]. E-mail: hofman@usc.edu

    2007-04-01

    The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated {beta}-galactosidase (SA-{beta}-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-{beta}-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.

  4. Prescription Drug Abuse

    MedlinePLUS

    ... street drugs. Why Do Some People Abuse Prescription Drugs? Some people experiment with prescription drugs because they ... friends — is actually breaking the law. Continue Which Drugs Are Abused? The most commonly used prescription drugs ...

  5. Teenagers and drugs

    MedlinePLUS

    ... and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... likely your teen's drug use will turn into drug abuse . You can find more information at http://teens. ...

  6. Diarrheal Disease in Show Swine

    E-print Network

    Lawhorn, D. Bruce

    2007-02-27

    Diarrhea, an important problem in show pigs, can be caused by poor nutrition, infectious diseases, internal parasites or a combination of factors. This publication explains how the cause is diagnosed and the illness treated....

  7. Co-lethality studied as an asset against viral drug escape: the HIV protease case

    PubMed Central

    2010-01-01

    Background Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. Results From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. Conclusions These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. Reviewers This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke. PMID:20565756

  8. [Generic drugs].

    PubMed

    Delporte, J P

    2002-01-01

    Various incentives will progressively increase the part of generic drugs on the Belgian market place and will more and more confront the prescriber with the problem of substitution. The equivalence between generic and brand name products and the fear, justified or not, at efficacy or patient safety levels in case of substitution are discussed on the basis of biopharmacy and pharmacokinetic concepts in connection with modalities generally adopted when requesting marketing authorisation. Considering the extent of their utilisation at international level and the low frequency of clinically significant problems linked to bioequivalency, limited to a small number of substances, prescribers should be soon released from their apprehensions on the quality of generic drugs. On another hand, they must be stimulated to be vigilant when they substitute a drug by any other one, especially in the cases of drugs, classes of drugs, or pharmaceutical forms considered as critical and when occurring to patients whose disease or physiological status are able to amplify bioequivalence problems. PMID:11899492

  9. Predicting the Onset of Sexual and Drug Risk Behaviors in HIV-Negative Youths with HIV-Positive Mothers: The Role of Contextual, Self-Regulation, and Social-Interaction Factors

    ERIC Educational Resources Information Center

    Mellins, Claude A.; Dolezal, Curtis; Brackis-Cott, Elizabeth; Nicholson, Ouzama; Warne, Patricia; Meyer-Bahlburg, Heino F. L.

    2007-01-01

    HIV-negative, inner-city adolescents with HIV-infected parents are considered to be at high risk for acquiring HIV themselves. Using a modified theory of health behavior, this study examined the effects of maternal HIV infection and psychosocial variables on the onset of sexual and drug risk behavior in 144 HIV-negative adolescents with and…

  10. 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

  11. HIV infection in females dependent on drugs.

    PubMed

    Wai, B H; Singh, S; Varma, S L

    1996-03-01

    One hundred and seventy-one drug-dependent females in a drug rehabilitation centre were studied to estimate the prevalence of HIV infection among them. Twenty-four (14%) were positive on the Western Blot test. The presence of HIV infection was significantly correlated with syphilis (p < 0.03) and age (p < 0.001); 83% of those who were HIV positive were intravenous drug users. The need for harm reduction programmes to prevent spread of HIV infection among injecting drug users is stressed. PMID:8867206

  12. Diarrheal Disease in Show Swine 

    E-print Network

    Lawhorn, D. Bruce

    2007-02-27

    of gain. Lawsonia intracellularis is the causative bacterium. Though it is rarely the cause of diarrheal disease in show swine, veterinarians consider this organism as a potential cause when making a differ- ential diagnosis. L. intracellularis does.... TGE does not cause human disease. Clinical Diagnosis The stool of the normal pig should be firm and well- formed. When a normal show pig is on free-choice feed and water, the stool tends to loosen to the consistency of a cow patty as feed consumption...

  13. 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.

  14. Participation in drug treatment court and time to rearrest

    Microsoft Academic Search

    Duren Banks; Denise C. Gottfredson

    2004-01-01

    This study uses an experimental design to assess the impact of a drug treatment court on nonviolent felony offenders. The drug court program combines intensive supervision, judicial monitoring, drug testing, and drug treatment to reduce recidivism and other problem behaviors. Survival analyses showed that the drug court sample had a significantly longer time to first rearrest than the control sample.

  15. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided. PMID:11366758

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

    PubMed

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

    2014-07-11

    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. PMID:24960297

  17. Nuclear Positioning

    PubMed Central

    Gundersen, Gregg G.; Worman, Howard J.

    2013-01-01

    SUMMARY The nucleus is the largest organelle and is commonly depicted in the center of the cell. Yet during cell division, migration and differentiation, it frequently moves to an asymmetric position aligned with cell function. We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it. The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins. Finally, we discuss how nuclear position may influence cellular organization and signaling pathways. PMID:23498944

  18. Pembrolizumab Shows Promise for NSCLC.

    PubMed

    2015-06-01

    Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy. PMID:25895920

  19. The OOPSLA trivia show (TOOTS)

    Microsoft Academic Search

    Jeff Gray; Douglas C. Schmidt

    2009-01-01

    OOPSLA has a longstanding tradition of being a forum for discussing the cutting edge of technology in a fun and participatory environment. The type of events sponsored by OOPSLA sometimes border on the unconventional. This event represents an atypical panel that conforms to the concept of a game show that is focused on questions and answers related to OOPSLA themes.

  20. Managing Beef Cattle for Show

    E-print Network

    Herd, Dennis B.; Boleman, Chris; Boleman, Larry L.

    2001-11-16

    in show diets because of its rapid digestion and tendency to cause acido- sis (see the section on health). Oats are excellent for growth and development of steers or heifers. A mixture similar in nutrient content to oats can be formulated with a high...

  1. Microelectronic control of drug delivery.

    PubMed

    Guo, Xin Dong; Prausnitz, Mark R

    2012-07-01

    Microelectronic control of drug delivery devices enables precise management of drug delivery profiles. Iontophoresis patches offer microelectronic control over delivery in a noninvasive manner, but these are limited to the administration of relatively small molecules at small doses. Infusion pumps are widely used for delivery of insulin and other drugs; however, they require an invasive catheter that many patients find inconvenient and can be a site of infection. Implanted pumps avoid these problems, but they require long-term commitment associated with surgical implantation. An alternative is an implanted microchip containing many protected reservoirs filled with drug powder that is selectively released under microelectronic control. This device offers the promise of long-term drug stability in the solid state and precise digital drug dosing. Building on more than 10 years of preclinical studies, this wirelessly controlled microchip technology recently underwent a first-in-human clinical study. The microchip was implanted subcutaneously in the abdomen of eight female patients with osteoporosis. A remote operator was able to establish a wireless link with the microchip to program the schedule of human parathyroid hormone dosing from the device. This study showed that the wireless microchips produced pharmacokinetics similar to those from subcutaneous injections of the drug and produced less variable drug levels in the blood. There were also no toxic or adverse events due to the microchip or drug. This study represents an important step towards more widespread use of microelectronic control of drug delivery to improve pharmaceutical therapies. PMID:22905837

  2. Magic Carpet Shows Its Colors

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The upper left image in this display is from the panoramic camera on the Mars Exploration Rover Spirit, showing the 'Magic Carpet' region near the rover at Gusev Crater, Mars, on Sol 7, the seventh martian day of its journey (Jan. 10, 2004). The lower image, also from the panoramic camera, is a monochrome (single filter) image of a rock in the 'Magic Carpet' area. Note that colored portions of the rock correlate with extracted spectra shown in the plot to the side. Four different types of materials are shown: the rock itself, the soil in front of the rock, some brighter soil on top of the rock, and some dust that has collected in small recesses on the rock face ('spots'). Each color on the spectra matches a line on the graph, showing how the panoramic camera's different colored filters are used to broadly assess the varying mineral compositions of martian rocks and soils.

  3. Frequent childhood geographic relocation: its impact on drug use initiation and the development of alcohol and other drug-related problems among adolescents and young adults.

    PubMed

    DeWit, D J

    1998-01-01

    Early geographic relocation has been implicated as an important correlate of psychopathology, learning difficulties, and behavioural problems among child and adolescent populations, yet systematic studies of the potential influence of relocation on youthful drug use have not been conducted. This study explored the relationship between number of geographic moves before the age of 16 and the timing of onset of drug use and progression to drug-related problems. Data were obtained from 3,700 young adults aged 18 to 35 years participating in the 1990-1991 Ontario Mental Health Supplement, a large random probability survey of the residents of the Province of Ontario, Canada. Holding constant potential confounding factors, results showed highly significant positive relationships between moving and early initiation of illicit drugs including marijuana, hallucinogens, crack/cocaine, and illicit use of prescribed drugs. Among marijuana users, moving was also associated with a hastening of time to marijuana-related problems. Relationships between moving and measures of alcohol use/problems (onset of first drink, onset of any alcohol-related problem) were either weak or nonsignificant. Important sex differences were found, with statistically significant relationships between moving and early drug use initiation and progression occurring primarily among males. Future research is required to test for possible mediating mechanisms linking relocation with drug use as well as moderating influences. Efforts should also focus on finding out why drug use appears to be a more common response to relocation among boys. PMID:9768299

  4. Drug Filtering

    NSDL National Science Digital Library

    Lawrence F. Iles

    2010-01-01

    In this math meets health science activity, learners observe a model of exponential decay, and how kidneys filter blood. Learners will calculate the amount of a drug in the body over a period of time. Then, they will make and analyze the graphical representation of this exponential function. This lesson guide includes questions for learners, assessment options, extensions, and reflection questions.

  5. Drug Guide

    MedlinePLUS

    ... Bath Salts. Read More > Caffeine What is Caffeine? Caffeine is a psychoactive stimulant. Read More > Cocaine/Crack What is Cocaine? Cocaine is a drug extracted from the leaves of the coca plant. It is a potent brain stimulant and one ...

  6. Pig and the Poultry Show 

    E-print Network

    Sloan

    2009-01-01

    directed toward 1ncreasing d1gestibi11ty of the gra1n. Fitch and Wolberg (2l) found that 435 of the grain of Kansas Orange and 36K of the grain of Atlas Sorgo s1lage was voided intact in the animal's feces. Analysis of the vo1ded grains showed... whole kernels, but the starchy endosperm had been digested. Davis and Waldern (14) observed that 7. 1~~ of the kernels and 1. 2? of the whole s1lage DM appeared in the feces as whole kernels. The propor- tion of in v1tro digestible dry matter ( IVDDM...

  7. Managing Beef Cattle for Show 

    E-print Network

    Herd, Dennis B.; Boleman, Chris; Boleman, Larry L.

    2001-11-16

    . Protein supplements?Feeds such as cottonseed meal, soybean meal and linseed meal increase the protein content of the diet. Small amounts (less than 3 percent) of fish meal, dried blood meal, corn gluten meal, linseed meal and brewers or distillers grains... of nutritional ailments of acidosis, bloat and possibly founder. A big full middle on a steer can be more effectively controlled by limiting feed and water the last few weeks before show, not by elimi- nating hay from the diet. Hay should be free of mold, dust...

  8. 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...

  9. 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...

  10. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...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)...

  11. 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)...

  12. 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)...

  13. Drug models of schizophrenia.

    PubMed

    Steeds, Hannah; Carhart-Harris, Robin L; Stone, James M

    2015-02-01

    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

  14. 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.

  15. 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.

  16. 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.

  17. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

  18. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    1998-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the ?-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:9803978

  19. Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells

    PubMed Central

    Boussouar, Amina; Barette, Caroline; Nadon, Robert; Saint-Léger, Adelaļde; Broucqsault, Natacha; Ottaviani, Alexandre; Firozhoussen, Arva; Lu, Yiming; Lafanechčre, Laurence; Gilson, Eric; Magdinier, Frédérique; Ye, Jing

    2013-01-01

    We took advantage of the ability of human telomeres to silence neighboring genes (telomere position effect or TPE) to design a high-throughput screening assay for drugs altering telomeres. We identified, for the first time, that two dietary flavones, acacetin and chrysin, are able to specifically alleviate TPE in human cells. We further investigated their influence on telomere integrity and showed that both drugs drastically deprotect telomeres against DNA damage response. However, telomere deprotection triggered by shelterin dysfunction does not affect TPE, indicating that acacetin and chrysin target several functions of telomeres. These results show that TPE-based screening assays represent valuable methods to discover new compounds targeting telomeres. PMID:23962900

  20. Drug safety sciences and the bottleneck in drug development.

    PubMed

    Watkins, P B

    2011-06-01

    During a recent review of a new drug application for treatment of a chronic disease, US Food and Drug Administration (FDA) regulators agreed with the sponsor's assessment of efficacy. However, it was noted that two subjects receiving active treatment experienced abnormal liver chemistries that possibly, but not definitely, indicated a liver safety liability. The sponsor was told that a prerequisite for approval would be a new clinical trial involving 20,000 patients treated for 1 year, with 10,000 receiving the new drug and 10,000 receiving a comparator treatment. The sponsor is now faced with the substantial costs involved in undertaking such a large study, the loss of patent life during the conduct and analysis of the study, and the prospect of losing in-class market position. If the drug is ultimately approved, this detour will result in costs and potential revenue loss to the sponsor of well over $1 billion. PMID:21593756

  1. Screening for drugs in oral fluid: illicit drug use and drug driving in a sample of Queensland motorists.

    PubMed

    Davey, J; Leal, N; Freeman, J

    2007-05-01

    Police Services in a number of Australian states have indicated random roadside drug testing will be implemented to target drug driving. This paper outlines research conducted to provide an estimate of the prevalence of drug driving in a sample of Queensland drivers. Oral fluid samples were collected from 781 drivers who volunteered to participate at Random Breath Testing (RBT) sites in a large Queensland regional area. Illicit substances tested for included cannabis (delta 9 tetrahydrocannibinol [THC]), amphetamine type substances, heroin and cocaine. Drivers also completed a self-report questionnaire regarding their drug-related driving behaviour. Samples that were drug-positive at initial screening were sent to a government laboratory for confirmation. Oral fluid samples from 27 participants (3.5%) were confirmed positive for at least one illicit substance. The most common drugs detected in oral fluid were cannabis (delta 9 THC) (n = 13) followed by amphetamine type substances (n = 11). A key finding was that cannabis was also confirmed as the most common self-reported drug combined with driving and that individuals who tested positive to any drug through oral fluid analysis were also more likely to report the highest frequency of drug driving. Furthermore, a comparison between drug vs drink driving detection rates for the study period revealed a higher detection rate for drug driving (3.5%) vs drink driving (0.8%). This research provides evidence that drug driving is relatively prevalent on Queensland Roads. The paper will further outline the study findings and present possible directions for future drug driving research. PMID:17454020

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

    PubMed

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

    2014-01-01

    This article examines the US Army's Medical Review Officer (MRO) drug positive urinalysis evaluations from 2009 through 2012. We retrospectively analyzed nearly 70,000 MRO results by year, drug and Army component. Of the MRO reviewable positive results, the Army's unauthorized drug positive rate was 22.21%. The component rates were 20.81, 24.17 and 26.09% for the Active Duty, Reserve and National Guard, respectively. By drug, the average unauthorized rates over these 4 years were 13.78% for oxycodone, 24.62% oxymorphone, 18.56% d-amphetamine, 98.04% d-methamphetamine, 21.97% codeine, 45.21% morphine and 100% steroids. In 2012 testing began for hydrocodone and hydromorphone and their unauthorized rates were 12.32 and 15.04%, respectively. The Army's unauthorized drug positive rate peaked in 2012 when it increased over 44% from the previous year. The 2012 rates in decreasing order were steroids > D-methamphetamine > morphine > oxymorphone > oxycodone > codeine > D-amphetamine > hydromorphone > hydrocodone. This comprehensive analysis showed that the majority of the Army's MRO reviews were associated with the use of authorized prescriptions; however, there appears to be significant abuse of oxycodone and D-amphetamine. PMID:25002456

  3. Adolescents and Drug Abuse: Clinical Use of Urine Drug Screening.

    ERIC Educational Resources Information Center

    James, William H.; Moore, David D.

    1997-01-01

    Study examines the use of urine screening as a clinical diagnostic procedure to assess and monitor adolescents in a school-based outpatient program (N=296). Random screening provides little information regarding diagnostic level and pattern of drug use; however it may be helpful in bringing about positive behavior change. (EMK)

  4. Computational Techniques in Fragment Based Drug Discovery

    Microsoft Academic Search

    Hugo O. Villar; Mark R. Hansen

    2007-01-01

    Fragment based drug discovery is gaining acceptance as a complement to other more established techniques to identify leads and optimize drug candidates. In this review we illustrate areas where fragment based drug discovery has had an impact and point to some examples that show how fragment based analysis is being applied to new arenas. The traditional uses of computational methods

  5. Drug Filtering

    NSDL National Science Digital Library

    This lesson from Illuminations looks at exponential decay. The example of how kidneys filter blood is used. The material asks students to determine the amount of a drug that remains in the body over a period of time. Students will predict behavior by an exponential decay model and graph an exponential set of data. The lesson is appropriate for grades 9-12 and should require 1 class period to complete.

  6. Casimir experiments showing saturation effects

    E-print Network

    Bo E. Sernelius

    2009-10-27

    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 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.

  7. Casimir experiments showing saturation effects

    SciTech Connect

    Sernelius, Bo E. [Division of Theory and Modeling, Department of Physics, Chemistry and Biology, Linkoeping University, SE-581 83 Linkoeping (Sweden)

    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.

  8. Changing Positions.

    ERIC Educational Resources Information Center

    LaRose, Albert J.

    1987-01-01

    Describes one search for a middle- or upper-management academic library position within the context of concerns expressed by respondents in a 1985 survey of 1,400 American Library Association (ALA) members by Bernstein and Leach. Factors examined include locale; availability and salary; staff relations; the application; the screening process; and…

  9. 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

  10. 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.

  11. Drugs Approved for Leukemia

    MedlinePLUS

    ... Questions to Ask Your Doctor about Treatment Research Drugs Approved for Leukemia This page lists cancer drugs ... Hairy Cell Leukemia Drugs Approved for Meningeal Leukemia Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) ...

  12. Drug Plan Coverage Rules

    MedlinePLUS

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  13. 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.

  14. Therapeutic Drug Monitoring

    MedlinePLUS

    ... this website will be limited. 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. 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.

  16. Drug abuse first aid

    MedlinePLUS

    Drug abuse is the misuse or overuse of any medication or drug, including alcohol. This article discusses first ... use of these drugs is a form of drug abuse. Legitimate medications can be abused by people who ...

  17. Drugs and their effects

    NSDL National Science Digital Library

    Olivia Worland (Purdue University; Biological Sciences)

    2008-07-07

    There are many illegal drugs in existence. These drugs are often dangerous to create and extremely harmful to the human body. Drugs are addictive and can ultimately cause death if drug abuse or over-dosages occur.

  18. [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…

  19. 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,…

  20. Understanding and Counseling the Chronic Drug User

    ERIC Educational Resources Information Center

    Dyer, Wayne W.; Vriend, John

    1975-01-01

    The authors present a paradigm of external and internal thinking as these apply as causes for positive and negative emotional shifts. The concepts of internally and externally oriented thinking are discussed, and these are related to counseling the dependent drug user. Strategies for dealing with the dependent drug user are presented. (Author)

  1. Familiar drugs may prevent cancer

    Microsoft Academic Search

    R A Sharma; A J Gescher; K J OByrne; W P Steward

    2001-01-01

    Despite positive results in large scale chemoprevention trials, many physicians are unaware of the potential cancer preventive properties of drugs in common usage. The antioestrogen tamoxifen and the selective cyclo-oxygenase-2 inhibitor celecoxib have been licensed in the USA for the chemoprevention of breast and colorectal cancers respectively in selected high risk individuals. Similarly, folate and retinol have been shown to

  2. An Experimental Trial of Adaptive Programming in Drug Court: Outcomes at 6, 12 and 18 Months

    PubMed Central

    Marlowe, Douglas B.; Festinger, David S.; Dugosh, Karen L.; Benasutti, Kathleen M.; Fox, Gloria; Harron, Ashley

    2013-01-01

    Objectives Test whether an adaptive program improves outcomes in drug court by adjusting the schedule of court hearings and clinical case-management sessions pursuant to a priori performance criteria. Methods Consenting participants in a misdemeanor drug court were randomly assigned to the adaptive program (n = 62) or to a baseline-matching condition (n = 63) in which they attended court hearings based on the results of a criminal risk assessment. Outcome measures were re-arrest rates at 18 months post-entry to the drug court and urine drug test results and structured interview results at 6 and 12 months post-entry. Results Although previously published analyses revealed significantly fewer positive drug tests for participants in the adaptive condition during the first 18 weeks of drug court, current analyses indicate the effects converged during the ensuing year. Between-group differences in new arrest rates, urine drug test results and self-reported psychosocial problems were small and non-statistically significant at 6, 12 and 18 months post-entry. A non-significant trend (p = .10) suggests there may have been a small residual impact (Cramer's ? = .15) on new misdemeanor arrests after 18 months. Conclusions Adaptive programming shows promise for enhancing short-term outcomes in drug courts; however, additional efforts are needed to extend the effects beyond the first 4 to 6 months of enrollment. PMID:25346652

  3. 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…

  4. Systematic Drug Repositioning Based on Clinical Side-Effects

    Microsoft Academic Search

    Lun Yang; Pankaj Agarwal

    2011-01-01

    Drug repositioning helps fully explore indications for marketed drugs and clinical candidates. Here we show that the clinical side-effects (SEs) provide a human phenotypic profile for the drug, and this profile can suggest additional disease indications. We extracted 3,175 SE-disease relationships by combining the SE-drug relationships from drug labels and the drug-disease relationships from PharmGKB. Many relationships provide explicit repositioning

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

    PubMed

    Burillo-Putze, G; Dķaz, 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

  6. Positivity of Quasilocal Mass

    E-print Network

    Chiu-Chu Melissa Liu; Shing-Tung Yau

    2003-06-19

    Motivated by the important work of Brown adn York on quasilocal energy, we propose definitions of quasilocal energy and momentum surface energy of a spacelike 2-surface with positive intrinsic curvature in a spacetime. We show that the quasilocal energy of the boundary of a compact spacelike hypersurface which satisfies the local energy condition is strictly positive unless the spacetime is flat along the spacelike hypersurface.

  7. Drug use, drug prohibition and minority communities

    Microsoft Academic Search

    Patrick R. Clifford

    1992-01-01

    Drug problems, including alcohol and tobacco abuse, present major public health concerns for the American people. Drug abuse and its related difficulties have been associated with both increased morbidity and premature mortality. In the United States, ethnic minorities have experienced the overall negative impact of drug abuse much more severely than the general population. The impact of drug prohibition in

  8. drug sales

    Microsoft Academic Search

    Gerhard Nahler

    \\u000a Drug sales (in million US$) in the top seven European pharmaceutical markets were in 1995 as follows: Germany 16.4, France\\u000a 14.3, Italy 7.5, UK 6.0, Spain 4.6, Netherlands 2.0, Belgium 1.9; US: 52.5, Canada: 3.4, Japan: 26.8; the five leading therapeutic\\u000a category in the seven top European markets are cardiovasculars (11.7), alimentary\\/metabolism (9.1), CNS (6.2), anti-infectives\\u000a (5.3), and respiratory agents

  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. Repurposed drugs in metabolic disorders.

    PubMed

    Finsterer, Josef; Frank, Marlies

    2013-01-01

    Drug repurposing (drug repositioning, drug reprofiling, drug retasking) gains increasing importance as the development of new drugs becomes increasingly expensive. Though only a few compounds have been approved for new indications in the field of metabolic disorders, there are a number of substances which have the potential to become reprofiled in a new indication. Generally, reprofiled drugs for metabolic disorders can be classified in three groups. Group A contains those of which both, the original and repurposed indication, concern metabolic disorders. Group B comprises drugs, which were originally approved for non-metabolic disorders but show beneficial effects for metabolic disorders after repurposing. Group C comprises drugs, which were originally approved for metabolic disorders and are effective for non-metabolic disorders in their repurposed indication. Repurposed drugs in the field of metabolic disorders of group A include tetra-hydrobiopterin, originally indicated for phenylketonuria and now also approved for tetrahydrobiopterindeficiency, coenzyme-Q, originally approved for primary coenzyme-Q deficiency and reprofiled for statin-myopathy, and colesevelam, originally approved to reduce elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) and now being approved for type-2-diabetes. An example of group C is phenylbutyrate, which was originally approved for urea-cycle disorders and meanwhile gained approval for progressive familial intrahepatic cholestasis type 2 due to mutations in the ABCB11 gene. Still additional compounds used to treat metabolic (non-metabolic) disorders show promising effects in non-metabolic (metabolic disorders) after repurposing in cell and tissue models. Future investigations will need to identify which candidate drugs may leave the pipeline status to acquire approval for new indications. PMID:24059459

  11. Construct anticancer drug-drug correlation network

    Microsoft Academic Search

    Jiao Li; Pamela Crowell; Jake Yue Chen

    2009-01-01

    Network biology methods have been promising in linking diseases, genes, and drugs. In this study, we propose a novel computational method to construct drug-drug correlation networks, which consist of drug compounds as network graph nodes and correlated protein-drug profiles above a pre-determined threshold as network graph edges. This computational method is based on extensions of related work on identifying disease-specific

  12. 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.

  13. Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles.

    PubMed

    Xu, Rong; Wang, QuanQiu

    2015-06-01

    Targeted anticancer drugs such as imatinib, trastuzumab and erlotinib dramatically improved treatment outcomes in cancer patients, however, these innovative agents are often associated with unexpected side effects. The pathophysiological mechanisms underlying these side effects are not well understood. The availability of a comprehensive knowledge base of side effects associated with targeted anticancer drugs has the potential to illuminate complex pathways underlying toxicities induced by these innovative drugs. While side effect association knowledge for targeted drugs exists in multiple heterogeneous data sources, published full-text oncological articles represent an important source of pivotal, investigational, and even failed trials in a variety of patient populations. In this study, we present an automatic process to extract targeted anticancer drug-associated side effects (drug-SE pairs) from a large number of high profile full-text oncological articles. We downloaded 13,855 full-text articles from the Journal of Oncology (JCO) published between 1983 and 2013. We developed text classification, relationship extraction, signaling filtering, and signal prioritization algorithms to extract drug-SE pairs from downloaded articles. We extracted a total of 26,264 drug-SE pairs with an average precision of 0.405, a recall of 0.899, and an F1 score of 0.465. We show that side effect knowledge from JCO articles is largely complementary to that from the US Food and Drug Administration (FDA) drug labels. Through integrative correlation analysis, we show that targeted drug-associated side effects positively correlate with their gene targets and disease indications. In conclusion, this unique database that we built from a large number of high-profile oncological articles could facilitate the development of computational models to understand toxic effects associated with targeted anticancer drugs. PMID:25817969

  14. 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.

  15. 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.

  16. 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

  17. CCMR: Drug Delivery Using Nanoparticles

    NSDL National Science Digital Library

    Lin, Joyce

    2005-08-17

    Safe and nontoxic drug delivery is an ongoing area of research. Some current methods of drug delivery include the use of nanoparticles, hydrogels, dendrimers, and micelles. Nanoparticles can be used as vehicles in which to transport certain drugs to cancerous cells. A certain class of nanoparticles called clays is especially useful in synthesizing these drug delivery vehicles. Layered Double Hydroxides (LDHs) are a type of hydrotalcite clay with a structure similar to smectite clays. They have a general structure that consists of layers of metal hydroxides connected to a layer of another metal hydroxide by hydrogen bonding. LDHs are made up of layers of a trivalent and a divalently charged cation coordinated by six oxygen atoms. The resulting structure consists of two-dimensional sheets with positively charged faces and negatively charged edges that are stacked together via hydrogen bonding between hydroxyl groups on adjacent sheets. These sheets generally have a very high aspect ratio, resulting in a large surface area. The positively charged layers are balanced by the presence of anions between them. A wide variety of LDHs can be synthesized depending on the various cations and interlayer anions used. Characterization of the LDHs themselves as well as LDHs intercalated with the drugs was performed using X-ray diffraction and TEM and SEM microscopy.

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

    PubMed

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

    2015-08-01

    Background Parent or self-reported drug allergy claims frequently overestimate the real incidence of hypersensitivity reactions. A detailed and algorithmic diagnostic evaluation of drug reactions may allow a proper diagnosis. Objective The aim of this study was to determine the confirmation rates and risk factors for confirmed allergic drug reactions in children. Setting Mersin University Hospital in Turkey. Method The study consisted of children between ages of 8 months and 18 years with the history of suspected drug allergy as reported by the clinician or the patients. Parents were interviewed by a clinician to complete questionnaires that included questions about demographic data and characteristics of index drug reaction. Immediate reactions (IRs) were assessed with immediate-reading skin prick (SPT) and intradermal tests (IDT). Nonimmediate reactions (NIRs) were assessed with SPT, both early and delayed reading of IDT and patch tests. In case of negative skin tests, drug provocation tests were performed. The possible risk factors for confirmed drug allergy in univariate analysis (p < 0.1) were entered into the multivariate logistic regression analysis to determine independent predictors. Main outcome measure (1) Confirmation rates of drug allergy (2) Risk factors related to confirmed drug allergy in children. Results We evaluated a total of 180 suspected drug allergy reactions in 97 children, mainly to antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and anticonvulsants. Among all suspected allergic drug reactions, 97 (53.9 %) were immediate type and 83 (46.1 %) were non-immediate type. The average time interval between the reaction and allergologic work-up was 5 months. Drug allergy confirmation rates were 30.1 % for beta-lactams, 27.2 % for non-betalactams, 21.1 % for NSAIDs and 30 % for anticonvulsants. Eight of 54 confirmed NIRs showed positivity on immediate skin tests. Regulatory T cells, TGF-? and IL-10 levels were not different between groups with and without confirmed drug allergy. A strong family and personal history of drug allergy were found to be significantly related to the confirmed allergic drug reactions. Conclusion Parent or self-reported drug allergy should be evaluated with a standardized diagnostic work-up before strict prohibitions are made. In addition, family and personal histories of drug allergy were significant risk factors related to allergic drug reactions in children. PMID:25822038

  19. Family Role in the Reintegration Process of Recovering Drug AddictsA Qualitative Review of Israeli Offenders

    Microsoft Academic Search

    Lior Gideon

    2007-01-01

    In an outcome evaluation of recovering addicts who participated in a prison-based therapeutic community, 39 clients, a nonrandomized subsample, are interviewed about their rehabilitation and reintegration experience. This study focuses on the family as the main source of support and as an agent of change for the recovering drug addict. Although many studies show marriage and family to be positively

  20. Marathon Group Counseling with Illicit Drug Users: A Study of the Effects of Two Groups for 1 Month.

    ERIC Educational Resources Information Center

    Page, Richard C.

    1983-01-01

    Assessed the effectiveness of marathon counseling in producing lasting attitude changes in two groups of 28 imprisoned female drug users. Results showed both groups changed the attitudes of participants in positive ways, even though one group discussed unresolved issues of the past while the other discussed current conflicts. (JAC)

  1. 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…

  2. 2. VIEW OF ELEVATOR AT SECOND FLOOR BEDROOM, SHOWING ELEVATOR ...

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

    2. VIEW OF ELEVATOR AT SECOND FLOOR BEDROOM, SHOWING ELEVATOR CAR IN THE 'STUCK' POSITION, WHERE IT REMAINED FROM 1942 UNTIL REMOVAL IN 1985, LOOKING NORTHEAST - 72 Marlborough Street, Residential Hydraulic Elevator, Boston, Suffolk County, MA

  3. 6. VIEW FROM WESTERN ABUTMENT, SHOWING SIDE ELEVATION OF BRIDGE ...

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

    6. VIEW FROM WESTERN ABUTMENT, SHOWING SIDE ELEVATION OF BRIDGE No. Z-6 IN OPEN POSITION. - Chicago, Milwaukee & St. Paul Railway, Bridge No. Z-6, Spanning North Branch of Chicago River, South of Cortland Street, Chicago, Cook County, IL

  4. 8. VIEW, LOOKING NORTH, SHOWING NORTH SHORE AND OPERATOR'S HOUSE ...

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

    8. VIEW, LOOKING NORTH, SHOWING NORTH SHORE AND OPERATOR'S HOUSE WITH BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Mystic River Bridge, Spanning Mystic River between Groton & Stonington, Groton, New London County, CT

  5. 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

  6. 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

  7. The Impact of Trauma on Drug Users' Identities

    ERIC Educational Resources Information Center

    Etherington, Kim

    2007-01-01

    This article addresses drug users' identity construction, and invites counsellors, psychotherapists, researchers and others who work with drug misusers to notice how cultural and societal discourses can shape drug misusers' stories, and the positions from which helpers listen and respond to them. By representing and analysing parts of two life…

  8. The impact of trauma on drug users’ identities

    Microsoft Academic Search

    Kim Etherington

    2007-01-01

    This article addresses drug users’ identity construction, and invites counsellors, psychotherapists, researchers and others who work with drug misusers to notice how cultural and societal discourses can shape drug misusers’ stories, and the positions from which helpers listen and respond to them. By representing and analysing parts of two life stories, gathered as part of a wider narrative inquiry, this

  9. Misplaced marketing Misplaced fears of off label prescription drug marketing

    Microsoft Academic Search

    Chester S. Galloway

    2003-01-01

    The United State Food and Drug Administration gives approval for prescription drugs that are shown to be safe and effective to treat specific conditions. But once the drug is available, physicians can prescribe it for other “off label” uses, the positive therapeutic side effects that are discovered by the medical communities’ own information networks. The pharmaceutical manufacturers would like to

  10. The social constructions of drug users in professional interventions

    Microsoft Academic Search

    Pilar Albertķn; Jenny Cubells; Lupicinio Ińiguez

    2011-01-01

    This qualitative study analyses the construction of a subject who uses drugs (injected drugs) so as to offer psychosocial proposals for social healthcare interventions within this collective, and thereby contribute to social healthcare policies that optimise treatment for drug use. The results indicate that identity is connected to positions that are activated in interactions and relationships between users and professionals

  11. Workplace drug prevention programs: does zero tolerance work?

    Microsoft Academic Search

    Stephen Mehay; Natalie J. Webb

    2007-01-01

    Current drug policy in the US military mandates frequent random drug testing of service members and dismissal of those who test positive for illegal drugs. This article analyses the economic costs and benefits of this zero tolerance policy as applied in the US Navy. Program effects consist of the actual number of detected users and the predicted number of deterred

  12. Advantages of atmospheric pressure photoionization mass spectrometry in support of drug discovery.

    PubMed

    Cai, Yanxuan; Kingery, David; McConnell, Oliver; Bach, Alvin C

    2005-01-01

    The performance of the atmospheric pressure photoionization (APPI) technique was evaluated against five sets of standards and drug-like compounds and compared to atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). The APPI technique was first used to analyze a set of 86 drug standards with diverse structures and polarities with a 100% detection rate. More detailed studies were then performed for another three sets of both drug standards and proprietary drug candidates. All 60 test compounds in these three sets were detected by APPI with an overall higher ionization efficiency than either APCI or ESI. Most of the non-polar compounds in these three sets were not ionized by APCI or ESI. Analysis of a final set of 201 Wyeth proprietary drug candidates by APPI, APCI and ESI provided an additional comparison of the ionization techniques. The detection rates in positive ion mode were 94% for APPI, 84% for APCI, and 84% for ESI. Combining positive and negative ion mode detection, APPI detected 98% of the compounds, while APCI and ESI detected 91%, respectively. This analysis shows that APPI is a valuable tool for day-to-day usage in a pharmaceutical company setting because it is able to successfully ionize more compounds, with greater structural diversity, than the other two ionization techniques. Consequently, APPI could be considered a more universal ionization method, and therefore has great potential in high-throughput drug discovery especially for open access liquid chromatography/mass spectrometry (LC/MS) applications. PMID:15912481

  13. 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)…

  14. Twist Positivity

    NASA Astrophysics Data System (ADS)

    Jaffe, Arthur

    1999-11-01

    We study a heat kernel e-?H defined by a self-adjoint Hamiltonian H acting on a Hilbert space H, and a unitary representation U(g) of a symmetry group G of H, normalized so that the ground vector of H is invariant under U(g). The triple {H, U(g), H} defines a twisted partition function Zg and a twisted Gibbs expectation <·>g, Zg=TrH(U(g-1) e-?H) and <·>g=TrH(U(g-1)·e-?H)/TrH(U(g-1) e-?H). We say that {H, U(g), H} is twist positive if Zg>0. We say that {H, U(g), H} has a Feynman-Kac representation with a twist U(g), if one can construct a function space and a probability measure d?g on that space yielding (in the usual sense on products of coordinates) <·>g=?·d?g. Bosonic quantum mechanics provides a class of specific examples that we discuss. We also consider a complex bosonic quantum field ?(x) defined on a spatial s-torus Ts and with a translation-invariant Hamiltonian. This system has an (s+1)-parameter abelian twist group Ts×R that is twist positive and that has a Feynman-Kac representation. Given ??Ts and ??R, the corresponding paths are random fields ?(x, t) that satisfy the twist relation?(x, t+?)=ei???(x-?, t). We also utilize the twist symmetry to understand some properties of "zero-mass" limits, when the twist ?, ? lies in the complement of a set ?sing of singular twists.

  15. Dimeric drug polymeric nanoparticles with exceptionally high drug loading and quantitative loading efficiency.

    PubMed

    Cai, Kaimin; He, Xi; Song, Ziyuan; Yin, Qian; Zhang, Yanfeng; Uckun, Fatih M; Jiang, Chen; Cheng, Jianjun

    2015-03-18

    Encapsulation of small-molecule drugs in hydrophobic polymers or amphiphilic copolymers has been extensively used for preparing polymeric nanoparticles (NPs). The loadings and loading efficiencies of a wide range of drugs in polymeric NPs, however, tend to be very low. In this Communication, we report a strategy to prepare polymeric NPs with exceptionally high drug loading (>50%) and quantitative loading efficiency. Specifically, a dimeric drug conjugate bearing a trigger-responsive domain was designed and used as the core-constructing unit of the NPs. Upon co-precipitation of the dimeric drug and methoxypoly(ethylene glycol)-block-polylactide (mPEG-PLA), NPs with a dimeric drug core and a polymer shell were formed. The high-drug-loading NPs showed excellent stability in physiological conditions. No premature drug or prodrug release was observed in PBS solution without triggering, while external triggering led to controlled release of drug in its authentic form. PMID:25741752

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

    PubMed

    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

  17. 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

  18. [The development from drug to designer drug.

    PubMed

    Askaa, Bjarke; Horwitz, Henrik; Wųien, Vidar André; Hųgberg, 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

  19. AIDSinfo Drug Database

    MedlinePLUS

    ... APIs Widgets Order Publications Skip Nav AIDS info Drug Database Home > Drugs Espańol Text Size Drugs by class Collapse All | Expand All FDA-approved ... for health care providers and patients. Search the Drug Database Help × Search by drug name Performs a ...

  20. 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.

  1. Effects of Drug Abuse

    MedlinePLUS

    Listen to this page Effects of Drug Abuse Drug abuse hurts the people who take drugs AND the people around them, including families , kids , and ... HIV/AIDS Click here to learn more about effects of specific drugs . VIDEO: Why Are Drugs So ...

  2. 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

  3. GENDER-RESPONSIVE DRUG COURT TREATMENT

    PubMed Central

    Messina, Nena; Calhoun, Stacy; Warda, Umme

    2014-01-01

    This pilot study compared outcomes for 94 women offenders in San Diego County, California, who participated in four drug court programs. Women were randomized to gender-responsive (GR) programs using Helping Women Recover and Beyond Trauma or standard mixed-gender treatment. Data were collected at program entry, during treatment, and approximately 22 months after treatment entry. Bivariate and multivariate analyses were conducted. Results showed that GR participants had better in-treatment performance, more positive perceptions related to their treatment experience, and trends indicating reductions in posttraumatic stress disorder (PTSD) symptomology. Both groups improved in their self-reported psychological well-being and reported reductions in drug use (p < .06) and arrest (a diagnosis of PTSD was the primary predictor of reductions in rearrest, p < .04). Findings show some beneficial effects of adding treatment components oriented toward women’s needs. Significant questions remain, particularly around PTSD and whether it should be targeted to improve substance use outcomes for women. PMID:24839331

  4. HIV risks among injecting drug users in Vietnam: a review of the research evidence.

    PubMed

    Do, Khoi; Minichiello, Victor; Hussain, Rafat

    2012-09-01

    Injecting drug use plays a critical role in the transmission of HIV in Vietnam. This paper provides a comprehensive review of studies on risks of HIV infection among injecting drug users (IDUs) in Vietnam. Current research evidence shows that the age at which drug initiation starts is becoming younger and the transition time between non-injecting to injecting drug use becoming shorter. The practice of needle sharing and unprotected sex was quite common among the IDUs. Although most of the IDUs generally had good knowledge of HIV transmission routes, most IDUs were not aware of their infection status. Data from a national surveillance programme shows that a third of the IDUs were HIV positive. Amongst all HIV positive cases, almost two-thirds had a history of intravenous drug use. A number of studies have identified a range of risk factors and barriers to minimize the risk of HIV infection in IDUs. This paper discusses these issues and makes recommendations for changes to HIV/AIDS policies, programme interventions as well as future research on the topic. PMID:22716107

  5. Drugs, poverty, pregnancy, and foster care in Los Angeles, California, 1989 to 1991.

    PubMed Central

    Lewis, M A; Leake, B; Giovannoni, J; Rogers, K; Monahan, G

    1995-01-01

    To determine the characteristics and childbearing histories of women whose infants entered foster care in Los Angeles County, we examined the cases of 1,155 drug-using women whose infants were removed from them at birth and 236 non-drug-using women whose infants were also removed at birth by court order (July 1989 through March 1991). All of the women were indigent, and less than half had graduated from high school. The drug-using women frequently had criminal records, and more than a quarter were homeless. Many comparison women had mental health problems, and some (16.7%) were teenagers under court custody. Overall, 80% of all the children born to both groups of women were under court jurisdiction. Data obtained after study infants' births on 926 drug-using women observed for 18 months revealed that 22% had borne another infant who was placed in foster care; half of these infants had a positive drug immunoassay. Of the 185 non-drug-using women with 18-month follow-ups, 7.6% had borne another child who was in foster care. The magnitude of the repeated childbearing recorded among both groups of women in this study shows that preventive programs including family planning, mental health services, and drug prevention or rehabilitation programs have not reached this population. PMID:8533405

  6. Participatory design for drug-drug interaction alerts.

    PubMed

    Luna, Daniel; Otero, Carlos; Almerares, Alfredo; Stanziola, Enrique; Risk, Marcelo; Gonzįlez Bernaldo de Quirós, Fernįn

    2015-01-01

    The utilization of decision support systems, in the point of care, to alert drug-drug interactions has been shown to improve quality of care. Still, the use of these systems has not been as expected, it is believed, because of the difficulties in their knowledge databases; errors in the generation of the alerts and the lack of a suitable design. This study expands on the development of alerts using participatory design techniques based on user centered design process. This work was undertaken in three stages (inquiry, participatory design and usability testing) it showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction in the system. PMID:25991099

  7. Prescription Drugs and Cold Medicines

    MedlinePLUS

    ... Drugs of Abuse » Prescription Drugs & Cold Medicines Prescription Drugs & Cold Medicines Email Facebook Twitter What is Prescription Drug Abuse: Some medications have psychoactive (mind-altering) properties ...

  8. Characterization of drug-lysozyme conjugates by sheathless capillary electrophoresis-time-of-flight mass spectrometry.

    PubMed

    Haselberg, R; Harmsen, S; Dolman, M E M; de Jong, G J; Kok, R J; Somsen, G W

    2011-07-18

    Drug-protein conjugates have been widely used for the cell-specific targeting of drugs to cells that can bind and internalize the proteinaceous carrier. For renal drug targeting, lysozyme (LZM) can be used as an effective carrier that accumulates in proximal tubular cells. We used capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF-MS) for the characterization of different drug-LZM conjugates. A recently developed prototype porous tip sprayer was employed for sheathless electrospray ionization (ESI) CE-MS interfacing. In order to prevent adsorption of LZM conjugates to the capillary wall, a positively charged polyethylenimine capillary coating was used in combination with a low-pH background electrolyte. Drug-LZM products had been prepared by first coupling BOC-l-methionine hydroxysuccinimide ester (BOCmet) to lysine residues of LZM followed by conjugation with the kinase inhibitors LY364947, erlotinib, or Y27632 via a platinum(II)-based linker. CE-TOF-MS of each preparation showed narrow symmetrical peaks for the various reaction products demonstrating that drug-LZM conjugates remained stable during the CE analysis and subsequent ESI. Components observed in the drug-LZM products were assigned based on their relative migration times and on molecular mass as obtained by TOF-MS. The TOF-MS data obtained for the individual components revealed that the preparations contained LZM carrying one or two drug molecules, next to unmodified and BOCmet-modified LZM. Based on relative peak areas (assuming an equimolar response for each component) a quantitative conjugate profile could be derived for every preparation leading to drug loading values of 0.4-0.6 mol drug per mole protein. PMID:21645662

  9. The Effects of Social Contact on Drug Use: Behavioral Mechanisms Controlling Drug Intake

    PubMed Central

    Strickland, Justin C.; Smith, Mark A.

    2014-01-01

    The social environment plays a critical role in determining the likelihood that an individual will use drugs or will develop a drug use disorder. Recent evidence obtained from preclinical studies reveals that proximal social factors (i.e., those factors that are immediately present at the time of drug exposure) exert a particularly strong influence on both drug-seeking and drug-taking behavior. These studies are advancing our understanding of the role of the social environment in drug use by showing that the rewarding and reinforcing effects of drugs depend on (1) whether other individuals are immediately present and (2) whether those individuals are also using drugs. Furthermore, the preclinical literature examining the role of social learning in behavior maintained by nondrug reinforcers reveals a number of behavioral mechanisms by which social contact may influence drug use, as well as potential ways the social environment may be modified to prevent or reduce drug use. Additional research is needed to determine potential age and sex differences in the effects of social contact on drug use, to determine the generality of the current findings across different pharmacological classes of drugs, and to determine the role of social contact on drug intake during different transitional stages of drug use disorders; however, enough evidence now exists to begin implementing social interventions in clinical and at-risk populations. PMID:24188170

  10. Drugs Approved for Neuroblastoma

    MedlinePLUS

    ... Your Doctor about Treatment Research Drugs Approved for Neuroblastoma This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. ...

  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. National Drug IQ Challenge

    MedlinePLUS

    ... Challenge / 2014 National Drug IQ Challenge 2014 National Drug IQ Challenge Get Started! Correct/Total Questions: Score: ... 301-443-1124 See 2015's Chat Day Transcript Drugs: Shatter the Myths Order Free Copies Now for ...

  14. Save on Drug Costs

    MedlinePLUS

    ... Medicare 2015 costs at a glance Save on drug costs If you meet certain income and resource ... call 711. Other ways to lower your prescription drug costs Look into generic drugs. Ask your doctor ...

  15. Medication/Drug Allergy

    MedlinePLUS

    ... of Allergy & Clinical Immunology View full profile 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. Drug Overdose Deaths, Hospitalizations,

    E-print Network

    MacAdam, Keith

    Drug Overdose Deaths, Hospitalizations, and Emergency Department Visits in Kentucky, 2000 - 2012 #12; Kentucky Injury Preven on and Research Center Drug Overdose Deaths, Hospitaliza ons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Drug overdose deaths, 20002012

  17. Polymers influencing transportability profile of drug

    PubMed Central

    Gaikwad, Vinod L.; Bhatia, Manish S.

    2013-01-01

    Drug release from various polymers is generally governed by the type of polymer/s incorporated in the formulation and mechanism of drug release from polymer/s. A single polymer may show one or more mechanisms of drug release out of which one mechanism is majorly followed for drug release. Some of the common mechanisms of drug release from polymers were, diffusion, swelling, matrix release, leaching of drug, etc. Mechanism or rate of drug release from a polymer or a combination of polymers can be predicted by using different computational methods or models. These models were capable of predicting drug release from its dosage form in advance without actual formulation and testing of drug release from dosage form. Quantitative structure–property relationship (QSPR) is an important tool used in the prediction of various physicochemical properties of actives as well as inactives. Since last several decades QSPR has been applied in new drug development for reducing the total number of drugs to be synthesized, as it involves a selection of the most desirable compound of interest. This technique was also applied in predicting in vivo performance of drug/s for various parameters. QSPR serves as a predictive tool to correlate structural descriptors of molecules with biological as well as physicochemical properties. Several researchers have contributed at different extents in this area to modify various properties of pharmaceuticals. The present review is focused on a study of different polymers that influence the transportability profiles of drugs along with the application of QSPR either to study different properties of polymers that regulate drug release or in predicting drug transportability from different polymer systems used in formulations. PMID:24227951

  18. Drug Laws and Drug Law Enforcement

    Microsoft Academic Search

    Edward M. Brecher

    1986-01-01

    The problem of drug use and abuse has been present in American society ever since its inception, and many different laws have been enacted, both at the federal and state level, to combat drug use. The question that arises is how effective have these laws been or what has their impact been on reducing drug use within the United States?

  19. 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

  20. Drug induced `softening' in phospholipid monolayers

    NASA Astrophysics Data System (ADS)

    Basak, Uttam Kumar; Datta, Alokmay; Bhattacharya, Dhananjay

    2015-06-01

    Compressibility measurements on Langmuir monolayers of the phospholipid Dimystoryl Phospatidylcholine (DMPC) in pristine form and in the presence of the Non-steroidal Anti-inflammatory Drug (NSAID) Piroxicam at 0.025 drug/lipid (D/L) molecular ratio at different temperatures, show that the monolayer exhibits large increase (and subsequent decrease) in compressibility due to the drug in the vicinity of the Liquid Expanded - Liquid Condensed (LE-LC) phase transition. Molecular dynamics simulations of the lipid monolayer in presence of drug molecules show a disordering of the tail tilt, which is consistent with the above result.

  1. Generic drugs in dermatology: part II.

    PubMed

    Payette, Michael; Grant-Kels, Jane M

    2012-03-01

    In part I, we discussed new drug development, reviewed the history of the generic drug industry, described how generic drugs are approved by the US Food and Drug Administration, and defined the concepts of bioequivalence and therapeutic equivalence. Herein, we explore various factors impacting generic drug use across the different parties involved: the prescriber, the pharmacist, the patient, and the payer. We also include original cost analysis of dermatologic brand name and generic drugs and show the potential cost savings that can be achieved through generic substitution. We conclude with a review of the data addressing potential differences in the effectiveness of brand name versus generic drugs in dermatology. The cost of brand name and generic medications is highly variable by pharmacy, state, and payer. We used one source (www.drugstore.com) as an example and for consistency across all medications discussed herein. Prices included here may not reflect actual retail prices across the United States. PMID:22342022

  2. Provocation tests in diagnosing drug hypersensitivity.

    PubMed

    Bousquet, Philippe-Jean; Gaeta, Francesco; Bousquet-Rouanet, Laure; Lefrant, Jean-Yves; Demoly, Pascal; Romano, Antonino

    2008-01-01

    A position paper by the European Network for Drug Allergy (ENDA), the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity, defines drug provocation tests (DPTs) as "the controlled administration of a drug in order to diagnose drug hypersensitivity reactions". The DPT is widely considered to be the "gold standard" to establish or exclude the diagnosis of hypersensitivity to a certain substance, as it not only reproduces hypersensitivity symptoms, but also any other adverse clinical manifestation, irrespective of the mechanism. The DPT can be harmful and thus should only be considered after balancing the risk-benefit ratio in the individual patient. The ENDA position paper specifies two main indications for DPTs with the suspected compounds: 1. to exclude hypersensitivity in non-suggestive histories of drug hypersensitivity and in patients with non-specific symptoms, such as vagal symptoms under local anesthesia; 2. to establish a firm diagnosis in suggestive histories of drug hypersensitivity with negative, non-conclusive, or non-available allergologic tests. A positive DPT result optimizes allergen avoidance, while a negative one allows a false label of drug hypersensitivity to be removed. For these reasons, DPTs are often carried out to exclude a diagnosis of hypersensitivity to beta-lactams when other allergologic tests are negative. DPTs are also performed when the sensitivity of allergologic tests for evaluating allergic reactions to certain drugs, such as non-beta-lactam antibiotics, heparins, and glucocorticoids, is limited. On the other hand, DPTs are also performed to diagnose hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in subjects with the cross-reactive pattern, because both skin tests and in vitro diagnostic methods are ineffective in such patients. PMID:18991698

  3. Misuse of corticosteroids in some of the drugs dispensed as preparations from alternative systems of medicine in India.

    PubMed

    Gupta, S K; Kaleekal, T; Joshi, S

    2000-12-01

    Screening for corticosteroids carried out on 120 samples of alternative medicines which were dispensed to patients suffering mainly from asthma, arthritis, etc., showed that 38.32% of them were adulterated with steroids. Most of these samples were submitted for screening by either a medical practitioner or the patients themselves, who suspected effects of steroids from these drugs. The percentage of steroid positivity was determined in ayurvedic drugs, homeopathic drugs, and unknown or other category of drugs. The presence of steroids in these drugs given for different ailments such as asthma, arthritis, and unknown/other ailments was also tabulated. The results show that a high percentage of these samples contained corticosteroids, however, the distribution of positivity amongst groups was not statistically significant. The lack of proper quality control mechanisms to verify ingredients or efficacy of 'alternative medicines' has led to the proliferation of the practice of dispensing spurious drugs containing corticosteroids as alternative medicines. This study aims to highlight the existence of 'quick fix' remedies dispensed as 'alternative medicines' which not only cause extensive adverse health effects to the patients but also bring alternative systems of medicines into disrepute. The deliberate contamination of corticosteroids with alternative systems of medicine by some practitioners is a cause of great concern. Such practices may not only disgrace alternative systems of medicine but may also lead to adverse side-effects on chronic exposure. PMID:11338919

  4. 28. VIEW SOUTHWEST, EAST ABUTMENT SHOWING BASCULE LEAF IN RAISED ...

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

    28. VIEW SOUTHWEST, EAST ABUTMENT SHOWING BASCULE LEAF IN RAISED POSITION WITH THE EXTREME UPPER PORTION OF THE BASCULE RACK GEAR SHOWING IN THE LOWER RIGHT PORTION OF THE PHOTOGRAPH - Tomlinson Bridge, Spanning Quinnipiac River at Forbes Street (U.S. Route 1), New Haven, New Haven County, CT

  5. 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

  6. Current research in drug metabolism, drug transport and drug development.

    PubMed

    Johansson, Inger; Ingelman-Sundberg, Magnus

    2008-11-01

    The field of drug metabolism, drug transport and drug development is rapidly advancing. The fast progress of genomic knowledge, as well as improvements and development of novel methods, makes this field particularly dynamic. These advancements encompass the understanding of epigenetics in the regulation of the enzymes, novel animal model systems that allow the study of endogenous and exogenous function of the gene products, the development of P450 enzymes as drug targets and novel methods for studying ADME aspects during drug development. In order to give an update of the current situation in the field, the 17th International Symposium of Microsomes and Drug Oxidations, chaired by Larry Kaminsky, was held in Saratoga July 6-10, 2008, attracting 310 participants. The meeting consisted of 8 plenary sessions, 12 symposia with a total of 60 lectures and 185 abstracts. This report provides a summary of the meeting. PMID:19180270

  7. Drugs in development for tuberculosis.

    PubMed

    Ginsberg, Ann M

    2010-12-01

    Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain. These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues; rising and disturbing rates of multidrug- and extensively drug-resistant TB; the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co-epidemic. Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first- and second-line TB drugs. Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient age. This article reviews the challenges faced by those trying to develop these novel regimens and the key agents currently in clinical testing for TB; the latter are organized for discussion into three categories: (i) novel drugs (TMC207, SQ109, sudoterb [LL3858]); (ii) present first-line TB drugs being re-evaluated to optimize their efficacy (rifampicin, rifapentine); and (iii) currently licensed drugs for other indications and 'next-generation' compounds of the same chemical class being repurposed for TB (gatifloxacin and moxifloxacin; linezolid, PNU100480 and AZD5847; metronidazole, OPC-67683 and PA-824). PMID:21080738

  8. Obese women show greater delay discounting than healthy-weight women

    Microsoft Academic Search

    Rosalyn E. Weller; Edwin W. Cook; Kathy B. Avsar; James E. Cox

    2008-01-01

    Delay discounting (DD) is a measure of the degree to which an individual is driven by immediate gratification vs. the prospect of larger, but delayed, rewards. Because of hypothesized parallels between drug addiction and obesity, and reports of increased delay discounting in drug-dependent individuals, we hypothesized that obese individuals would show higher rates of discounting than controls. Obese and healthy-weight

  9. Forensic toxicological analyses of drugs in tissues in formalin solutions and in fixatives.

    PubMed

    Uekusa, Kyoko; Hayashida, Makiko; Ohno, Youkichi

    2015-04-01

    Forensic toxicological drug analyses of human specimens are usually performed immediately after autopsy or on frozen preserved tissues. Occasionally, cases require analysis of drugs from tissues fixed in formalin solution. To improve the estimation of the level of drug in tissues following formalin fixation, we studied drug concentrations in human tissues, liver and kidney, that were collected from a drug-positive autopsy case. Parts of tissues were preserved in formalin solution for 1, 3, 6 and 13 months. Tissues obtained before and after preservation, along with tissue-exposed fixatives, were assayed using gas chromatography-mass spectrometry; all of the samples were assayed for the presence of drugs and changes in the drug concentrations both before and after preservation in formalin. Concentrations of assayed drugs decreased upon fixation in formalin; levels of these drugs did not necessarily show further decreases during subsequent storage in fixative, up to 13 months. Distinct trends in drug levels were found in liver and kidney. In liver, the levels of chlorpromazine, levomepromazine, and promethazine decreased to 23-39% at 1 month after preservation; all 3 of these drugs were detected at all tested time points of preservation. Bromazepam was not detected at 13 months after preservation. Milnacipran was the most unstable after preservation in formalin solution among all of the assayed drugs. In kidney, all assayed drugs exhibited reduced stability during preservation compared to levels in liver. Methamphetamine and methylenedioxymethamphetamine were not detected in any time points of tissues. The proportions of the drugs that remained within the tissues differed between liver and kidney. Also, S-oxide compounds of chlorpromazine and levomepromazine, which were not observed before preservation, were detected in fixed liver tissues and their fixatives at 3, 6 and 13 months of preservation. These results suggest that analyses in formalin-fixed tissues need to include analysis of various organ-tissues and their fixatives at multiple time points for the duration of preservation. These analyses should include detection of chemical degradation/denaturation products, such as S-oxides of chlorpromazine and levomepromazine. PMID:25700112

  10. A potential role for creatine in drug abuse?

    PubMed

    D'Anci, Kristen E; Allen, Patricia J; Kanarek, Robin B

    2011-10-01

    Supplemental creatine has been promoted for its positive health effects and is best known for its use by athletes to increase muscle mass. In addition to its role in physical performance, creatine supplementation has protective effects on the brain in models of neuronal damage and also alters mood state and cognitive performance. Creatine is found in high protein foods, such as fish or meat, and is also produced endogenously from the biosynthesis of arginine, glycine, and methionine. Changes in brain creatine levels, as measured using magnetic resonance spectroscopy, are seen in individuals exposed to drugs of abuse and depressed individuals. These changes in brain creatine indicate that energy metabolism differs in these populations relative to healthy individuals. Recent work shows that creatine supplementation has the ability to function in a manner similar to antidepressant drugs and can offset negative consequences of stress. These observations are important in relation to addictive behaviors as addiction is influenced by psychological factors such as psychosocial stress and depression. The significance of altered brain levels of creatine in drug-exposed individuals and the role of creatine supplementation in models of drug abuse have yet to be explored and represent gaps in the current understanding of brain energetics and addiction. PMID:21399936

  11. Drug delivery by tattooing to treat cutaneous leishmaniasis.

    PubMed

    Shio, Marina Temi; Paquet, Marilene; Martel, Caroline; Bosschaerts, Tom; Stienstra, Stef; Olivier, Martin; Fortin, Anny

    2014-01-01

    This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites. Based on this, in vivo efficacy is demonstrated using a 10 day tattooing-mediated treatment in mice infected with L. major and L. mexicana. In both models this regimen results in rapid clinical recovery with complete regression of skin lesions by Day 28. Parasite counts and histopathology examination confirm high treatment efficacy at the parasitic level. Low amount of drug required for tattooing combined with fast clinical recovery may have a positive impact on CL patient management. This first example of tattoo-mediated drug delivery could open to new therapeutic interventions in the treatment of skin diseases. PMID:24561704

  12. Anti-anginal drugs

    PubMed Central

    Goldbarg, Alberto; Paxinos, James; Miller, Russell R.

    1970-01-01

    This review of studies on anti-anginal agents and their use in the anginal syndrome shows nitroglycerin to be unsurpassed in clinical effectiveness. It has a rapid onset of action. Its duration of action is relatively short but the need for a more prolonged effect has not been demonstrated. Most anginal attacks subside upon resting and the requirement for relief is immediate rather than prolonged. A long-acting anti-anginal agent would have some value if it could prevent precipitation of an anginal episode but there is no convincing evidence to indicate that these drugs have this capability. In general, clinical experience with long-acting nitrites is relatively unsatisfactory.

  13. Therapeutic drug monitoring of old and newer anti-epileptic drugs.

    PubMed

    Neels, Hugo M; Sierens, Ann C; Naelaerts, Kristine; Scharpé, Simon L; Hatfield, George M; Lambert, Willy E

    2004-01-01

    The aim of the present paper is to provide information concerning the setting up and interpretation of therapeutic drug monitoring (TDM) for anti-epileptic drugs. The potential value of TDM for these drugs (including carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pheneturide, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide) is discussed in relation to their mode of action, drug interactions and their pharmacokinetic properties. The review is based upon available literature data and on observations from our clinical practice. Up until approximately 15 years ago anti-epileptic therapeutics were restricted to a very few drugs that were developed in the first half of the 20th century. Unfortunately, many patients were refractory to these drugs and a new generation of drugs has been developed, mostly as add-on therapy. Although the efficacy of the newer drugs is no better, there is an apparent improvement in drug tolerance, combined with a diminished potential for adverse drug interactions. All new anticonvulsant drugs have undergone extensive clinical studies, but information on the relationship between plasma concentrations and effects is scarce for many of these drugs. Wide ranges in concentrations have been published for seizure control and toxicity. Few studies have been undertaken to establish the concentration-effect relationship. This review shows that TDM may be helpful for a number of these newer drugs. PMID:15576287

  14. Dynorphin and the Pathophysiology of Drug Addiction

    PubMed Central

    Shippenberg, T.S.; Zapata, A.; Chefer, V.I.

    2009-01-01

    Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that may ensue. As drug use becomes more compulsive, motivation for natural rewards that normally drive behavior decreases. The discontinuation of drug use is associated with somatic signs of withdrawal, dysphoria, anxiety and anhedonia. These consequences of drug use are thought to contribute to the maintenance of drug use and to the reinstatement of compulsive drug use that occurs during the early phase of abstinence. Even, however, after prolonged periods of abstinence, 80-90% of human addicts relapse to addiction suggesting that repeated drug use produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response (habit) learning. A major goal of addiction research is the identification of the neural mechanisms by which drugs of abuse produce these effects. This article will review data showing that the dynorphin/?-opioid receptor system serves an essential function in opposing alterations in behavior and brain neurochemistry that occur as a consequence of repeated drug use and that aberrant activity of this system may not only contribute to the dysregulation of behavior that characterizes addiction but to individual differences in vulnerability to the pharmacological actions of cocaine and alcohol. We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/?-opioid receptor system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction. PMID:17868902

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

    PubMed

    Delaveris, Gerd Jorunn Mųller; 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

  16. 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

  17. Workplace drug testing, different matrices different objectives.

    PubMed

    Tsanaclis, Lolita M; Wicks, John F C; Chasin, Alice A M

    2012-02-01

    Drug testing is used by employers to detect drug use by employees or job candidates. It can identify recent use of alcohol, prescription drugs, and illicit drugs as a screening tool for potential health and safety and performance issues. Urine is the most commonly used sample for illicit drugs. It detects the use of a drug within the last few days and as such is evidence of recent use; but a positive test does not necessarily mean that the individual was impaired at the time of the test. Abstention from use for three days will often produce a negative test result. Analysis of hair provides a much longer window of detection, typically 1 to 3 months. Hence the likelihood of a falsely negative test using hair is very much less than with a urine test. Conversely, a negative hair test is a substantially stronger indicator of a non-drug user than a negative urine test. Oral fluid (saliva) is also easy to collect. Drugs remain in oral fluid for a similar time as in blood. The method is a good way of detecting current use and is more likely to reflect current impairment. It offers promise as a test in post-accident, for cause, and on-duty situations. Studies have shown that within the same industrial settings, hair testing can detect twice as many drug users as urine testing. PMID:22362574

  18. Inheritance and Drug Response

    Microsoft Academic Search

    Alan E. Guttmacher; Francis S. Collins; Richard Weinshilboum

    2003-01-01

    he promise of pharmacogenetics, the study of the role of in - heritance in the individual variation in drug response, lies in its potential to identify the right drug and dose for each patient. Even though individual dif- ferences in drug response can result from the effects of age, sex, disease, or drug inter- actions, genetic factors also influence both

  19. 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 ...

  20. Graphing Current Drug Data

    NSDL National Science Digital Library

    Graphing Current Drug Data gives (1) some current views on the drug issue, (2) a history of drug use, (3) specific data on alcohol, caffeine, cocaine, marijuana and nicotine, and (4) data on high school drug trends from 1975-1985. The unit could supply graphing data for any math class 7-12, and could also be used in a social studies class.

  1. discoveries in drugs and

    E-print Network

    Glasser, Benjamin J.

    New discoveries in drugs and medicinal products are happening rapidly.One of the greatest that developing new drugs requires an enormous amount of time and money. On av- erage, introducing a new drug product to market takes approximately 15 years and $650 million. A drug product consists of therapeutics

  2. Disentangling the Correlates of Drug Use in a Clinic and Community Sample: A Regression Analysis of the Associations between Drug Use, Years-of-School, Impulsivity, IQ, Working Memory, and Psychiatric Symptoms

    PubMed Central

    Heyman, Gene M.; Dunn, Brian J.; Mignone, Jason

    2014-01-01

    Years-of-school is negatively correlated with illicit drug use. However, educational attainment is positively correlated with IQ and negatively correlated with impulsivity, two traits that are also correlated with drug use. Thus, the negative correlation between education and drug use may reflect the correlates of schooling, not schooling itself. To help disentangle these relations we obtained measures of working memory, simple memory, IQ, disposition (impulsivity and psychiatric status), years-of-school and frequency of illicit and licit drug use in methadone clinic and community drug users. We found strong zero-order correlations between all measures, including IQ, impulsivity, years-of-school, psychiatric symptoms, and drug use. However, multiple regression analyses revealed a different picture. The significant predictors of illicit drug use were gender, involvement in a methadone clinic, and years-of-school. That is, psychiatric symptoms, impulsivity, cognition, and IQ no longer predicted illicit drug use in the multiple regression analyses. Moreover, high risk subjects (low IQ and/or high impulsivity) who spent 14 or more years in school used stimulants and opiates less than did low risk subjects who had spent <14?years in school. Smoking and drinking had a different correlational structure. IQ and years-of-school predicted whether someone ever became a smoker, whereas impulsivity predicted the frequency of drinking bouts, but years-of-school did not. Many subjects reported no use of one or more drugs, resulting in a large number of “zeroes” in the data sets. Cragg’s Double-Hurdle regression method proved the best approach for dealing with this problem. To our knowledge, this is the first report to show that years-of-school predicts lower levels of illicit drug use after controlling for IQ and impulsivity. This paper also highlights the advantages of Double-Hurdle regression methods for analyzing the correlates of drug use in community samples. PMID:25009508

  3. Position Announcement Fellowship/Contract Position

    E-print Network

    Yamamoto, Keith

    Position Announcement Fellowship/Contract Position Epidemiologist ­ Monitoring & Evaluation. This 2-year contract position will be located in the Epidemiology and Strategic Information Branch (ESIB Conduct a review of existing tools, draft minimum data elements, draft data collection tools, recommend

  4. [Drug residues in food fish].

    PubMed

    Hartmann, S; Friedrich, A; Baum, F; Goetze, L

    1990-07-01

    The present paper reviews different possibilities of pharmacolegal residues in fish. Sometimes the treatment of fish with registered drugs in therapeutical dosage is provable in spite of keeping the withdrawal time. To that experiences of the persistence and values of Chloramphenicol, Chlortetracycline and Furazolidone proved after therapeutical treatment in fish correlated to the water temperature are compared with results of experiments documented in literature. Investigations on the residues of Enrofloxacin after application of different doses to rainbow trout were carried out. Sometimes the proof of drug residues in fish can be done without an advanced treatment. The recontamination of fish with drugs or their metabolites in environment is discussed as a possibility for drug residues. The carry-over-effect of drug during the animal food production can be also the reason for residues in fish. Experiments with Chloramphenicol contaminated feed in rainbow trout show residues in muscle of fish higher than 10 ppb during the feeding period. Finally the results of residues different drug used in fish--given in literature--are collected in two tables. PMID:2205463

  5. Comparison of caspase-3 activation in tumor cells upon treatment of chemotherapeutic drugs using capillary electrophoresis.

    PubMed

    Sha, Shuang; Jin, Honglin; Li, Xiao; Yang, Jie; Ai, Ruiting; Lu, Jinling

    2012-05-01

    Caspases play important roles in cell apoptosis. Measurement of the dynamics of caspase activation in tumor cells not only facilitates understanding of the molecular mechanisms of apoptosis but also contributes to the development, screening, and evaluation of anticancer drugs that target apoptotic pathways. The fluorescence resonance energy transfer (FRET) technique provides a valuable approach for defining the dynamics of apoptosis with high spatio-temporal resolution. However, FRET generally functions in the single-cell level and becomes ineffective when applied in the high throughput detection of caspase activation. In the current study, a FRET sensor was combined with capillary electrophoresis (CE) to achieve a high throughput method for cellular caspase detection. The FRET-based CE system is composed of a homemade CE system and a laser source for detecting the dynamics of caspase-3 in various cells expressing sensors of caspase-3 that have been treated with anticancer drugs, such as cell cycle-independent drug cisplatin and specific cell cycle drugs camptothecin and etoposide, as well as their combination with tumor necrosis factor (TNF). A positive correlation between the caspase-3 activation velocity and drug concentration was observed when the cells were treated with cisplatin, but cells induced by camptothecin and etoposide did not show any apparent correlation with their concentrations. Moreover, different types of cells presented distinct sensitivities under the same drug treatment, and the combination treatment of TNF and anticancer drugs significantly accelerated the caspase-3 activation process. Its high throughput capability and detection sensitivity make the FRET-based CE system a useful tool for investigating the mechanisms of anticancer drugs and anticancer drug screening. PMID:22528748

  6. Smart drugs: green shuttle or real drug?

    PubMed

    Cornara, L; Borghesi, B; Canali, C; Andrenacci, M; Basso, M; Federici, S; Labra, M

    2013-11-01

    We have combined morphological, molecular, and chemical techniques in order to identify the plant and chemical composition of some last-generation smart drugs, present on the market under the following names: Jungle Mistic Incense, B-52, Blendz, and Kratom 10x. Micromorphological analyses of botanical fragments allowed identification of epidermal cells, stomata, trichomes, starch, crystals, and pollen. DNA barcoding was carried out by the plastidial gene rbcL and the spacer trnH-psbA as universal markers. The combination of morphological and molecular data revealed a mixture of plants from different families, including aromatic species, viz., Lamiaceae and Turneraceae. GC-MS and LC-MS analyses on ethanol or methanol extracts showed the presence of synthetic cannabinoids, including JWH-250 in Jungle, JWH-122 in B-52, and JWH-073 and JWH-018 in Blendz. In Kratom 10x, only the indole alkaloid mitragynine was detected. All the identified synthetic cannabinoids, apart from mitragynine, are under the restriction of law in Italy (TU 309/90). Synthetic cannabinoid crystals were also identified by scanning electron microscopy and energy dispersive X-ray spectroscopy, which also detected other foreign organic chemicals, probably preservatives or antimycotics. In Kratom only leaf fragments from Mitragyna speciosa, containing the alkaloid mitragynine, were found. In the remaining products, aromatic plant species have mainly the role of hiding synthetic cannabinoids, thus acting as a "green shuttle" rather than as real drugs. Such a multidisciplinary approach is proposed as a method for the identification of herbal blends of uncertain composition, which are widely marketed in "headshops" and on the Internet, and represent a serious hazard to public health. PMID:23842669

  7. Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery

    PubMed Central

    2015-01-01

    Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy. PMID:24483627

  8. Drug problems in China: recent trends, countermeasures, and challenges.

    PubMed

    Chen, Zhonglin; Huang, Kaicheng

    2007-02-01

    Drug crime in China is on an overall rising trend. Major drug crime cases are becoming more common, the types of drugs being trafficked are more diverse, and the smuggling and trafficking of drugs into the country and the smuggling of precursor chemicals out of the country have formed a bidirectional cycle. Drug crimes in China have also begun to show a conspicuous trend of internationalization. China's main countermeasures against drug crimes have been to pass new laws and regulations against drugs, to increase the efforts to eradicate cultivation, to establish and expand "drug-free communities" programs, and to strengthen international cooperation in antidrug campaigns. The existing problems demand prompt solutions, which include a shortage of funding and lack of accurate knowledge about prevalence of drug abuse and related data for scientifically studying the drug problems. PMID:17210659

  9. Drug–Drug Interaction Prediction Assessment

    Microsoft Academic Search

    Jihao Zhou; Zhaohui Qin; Quinney K. Sara; Seongho Kim; Zhiping Wang; Stephen D. Hall; Lang Li

    2009-01-01

    Model-based drug–drug interaction (DDI) is an important in-silico tool to assess the in vivo consequences of in vitro DDI. Before its general application to new drug compounds, the DDI model is always established from known interaction data. For the first time, tests for difference and equivalent tests are implemented to compare reported and model-base simulated DDI (log AUCR) in the

  10. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID:22043389

  11. Therapeutic drug monitoring of cytotoxic drugs

    PubMed Central

    Lennard, L

    2001-01-01

    Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are several reasons, but one major drawback is the lack of established therapeutic concentration ranges. Combination chemotherapy makes the establishment of therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as when that drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centres, and some of these protocols are now part of large multicentre trials. Nonetheless, methotrexate is the only agent which is routinely monitored in most treatment centres. An additional factor, especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes which play a major role in drug metabolism. Monitoring of therapy could include assay of phenotypic enzyme activities or genotype in addition to, or instead, the more traditional measurement of parent drug or drug metabolites. The cytotoxic activities of mercaptopurine and fluorouracil are regulated by thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD), respectively. Lack of TPMT functional activity produces life-threatening mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can influence the bioavailability, pharmacokinetics, toxicity and efficacy of their substrate drugs. PMID:11564055

  12. The calibration shows a linear relationship between the diffraction ring diameter and axial position.

    E-print Network

    Petta, Jason

    with a Tunable Acoustic Gradient Lens Stefanos Logothetis1, Ting-Hsuan Chen2, Craig B. Arnold2 1. Haverford, Princeton, NJ, 08540 Abstract Our work focuses on using a tunable acoustic gradient (TAG) lens in order Arnold. "Multiscale Bessel beams generated by a tunable acoustic gradient index of refraction lens

  13. 1979-80 Financial Statistics for Current Cost of Education... Showing San Joaquin Delta College Position...

    ERIC Educational Resources Information Center

    DeRicco, Lawrence A.

    The costs of education per unit of Average Daily Attendance (ADA) are detailed in this two-part report for 70 California community college districts for the academic year 1979-80. Both Part I, which presents data excluding non-resident ADA, and Part II, which presents figures including non-resident ADA, begin with tables which rank order the…

  14. Many sequence-specific chromatin modifying protein-binding motifs show strong positional

    E-print Network

    Marińo-Ramķrez, Leonardo

    for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8900 Rockville Pike Marin~ o-Rami´rez3 and David Landsman1, * 1 Computational Biology Branch, National Center

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

    E-print Network

    Atlantic Ocean fishing trip, where commercial longline gear was regularly used by southern Spanish Spanish fishermen operating in the Atlantic Ocean and Mediterranean Sea according to their experience (1981) observed, through radio-tracking, that in the Atlantic Ocean swordfish follow isoluminic

  16. 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)

  17. Drug and Alcohol Arrests Increased in 1999.

    ERIC Educational Resources Information Center

    Nicklin, Julie L.

    2001-01-01

    U.S. Department of Education (DOE) data showed a 1999 increase in drug and alcohol arrests on college campuses. Also, the number of reported sex offenses rose by 6 percent from 1998-99. Some experts question the validity of the year-to-year comparisons and the DOE data. Presents statistics on sex offenses, drug use, and drinking and football. (SM)

  18. 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

  19. Magnetic nanoparticles with a pH-sheddable layer for antitumor drug delivery.

    PubMed

    Wang, Jingjing; Gong, Chu; Wang, Yinong; Wu, Guolin

    2014-06-01

    A dually responsive nanocarrier with a multilayer core-shell architecture was prepared based on Fe3O4@SiO2 nanoparticles successively coated with poly(benzyl L-aspartate) (PBLA) and poly(ethylene glycol) (PEG) for the purpose of tumor specific drug delivery applications. In this system, PEG chains are connected to the surface via pH-sensitive benzoic-imine bonds and serve as a pH-sheddable hydrophilic corona. Meanwhile, the PBLA segments serve as a hydrophobic middle layer used to load the drugs via hydrophobic interactions. The Fe3O4@SiO2 nanoparticle functions as a superparamagnetic core used to direct the drug loaded nanocarrier to the target pathological site. The obtained materials were characterized with FT-IR, (1)H NMR, dynamic light scattering, zeta-potential, TEM, TGA, and hysteresis loop analysis. An anticancer drug doxorubicin (DOX) was selected as the model drug loaded into the nanocarrier, which was relatively stable under physiological conditions due to its neutral hydrophilic shell, and could quickly release the drug in response to increased acidity via shedding of the PEG shells through cleavage of the intermediate benzoic-imine bonds. Meanwhile, the neutral shell shedding would reveal a positively charged nanoparticle surface that is readily taken up by tumor cells. These pH- and magnetic-responsive nanoparticles showed significant potential for use in the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy. PMID:24768265

  20. 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.

  1. 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.

  2. Drug specificity in drug versus food choice in male rats.

    PubMed

    Tunstall, Brendan J; Riley, Anthony L; Kearns, David N

    2014-08-01

    Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena. PMID:24886157

  3. Synthesis and characterization of silane coated magnetic nanoparticles/glycidylmethacrylate-grafted-maleated cyclodextrin composite hydrogel as a drug carrier for the controlled delivery of 5-fluorouracil.

    PubMed

    Anirudhan, Thayyath S; Divya, Peethambaran L; Nima, Jayachandran

    2015-10-01

    A novel drug delivery system (DDS), 3-methacryloxypropyl trimethoxy silane coated magnetic nanoparticles polymerized with glycidylmethacrylate-grafted-maleated cyclodextrin (MPTMS-MNP-poly-(GMA-g-MACD)) was prepared in the presence of ethyleneglycoldimethacrylate as cross-linker and a,a'-azobisisobutyronitrile as initiator and characterized by means of SEM, FT-IR, XRD, DLS, VSM and TEM. The encapsulation efficiency (EE) and drug loading efficiency (DLE) of the DDS were tested using various formulations of DDS. The DDS showed activity against gram positive and negative bacteria. The cytotoxicity studies were also performed using MCF-7 (human breast carcinoma) cells and found that the drug carrier is biocompatible and it shows sustained and controlled release of drug to the targeted site. The drug release mechanism was found to obey non-Fickian diffusion (n=0.709) method where polymer relaxation and drug diffusion played important roles in drug release. In this DDS, advantages of core magnetic nanoparticles and host-guest interactions of ?-CD were combined for the controlled delivery of 5-Fluorouracil (5-FU) to maintain the therapeutic index of the drug. PMID:26117779

  4. 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

  5. Granulomatous Drug Eruptions.

    PubMed

    Dodiuk-Gad, Roni P; Shear, Neil H

    2015-07-01

    Granuloma formation is usually regarded as a means of defending the host from persistent irritants of either exogenous or endogenous origin. Noninfectious granulomatous disorders of the skin encompass a challenging group of diseases owing to their clinical and histologic overlap. Drug reactions characterized by a granulomatous reaction pattern are rare, and defined by a predominance of histiocytes in the inflammatory infiltrate. This review summarizes current knowledge on the various types of granulomatous drug eruptions, focusing on the 4 major types: interstitial granulomatous drug reaction, drug-induced accelerated rheumatoid nodulosis, drug-induced granuloma annulare, and drug-induced sarcoidosis. PMID:26143430

  6. Ask Your Pharmacist Generic Drugs

    E-print Network

    Ask Your Pharmacist Generic Drugs ...real medicines at high quality, low cost What Is a Generic Drug? A drug patent gives a drug company the sole right to sell a new drug. The company sells its new drug under its own brand name. By law, other companies cannot sell this drug until the term

  7. 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

  8. Anxiety sensitivity and self-reported reasons for drug use.

    PubMed

    Stewart, S H; Karp, J; Pihl, R O; Peterson, R A

    1997-01-01

    Two studies examined the relationships between anxiety sensitivity (AS), drug use, and reasons for drug use. In Study 1, 229 university students (57% F) completed the Anxiety Sensitivity Index (ASI) and a drug use survey, assessing use of a variety of drugs within the last month, and coping reasons for drug use. Consistent with a modified tension-reduction hypothesis, ASI scores were positively correlated with the number of both anxiety- and depression-related reasons for drug use endorsed. In Study 2, 219 university students (74% F) completed the ASI and a drug use survey, assessing use of several drugs (e.g., alcohol, cigarettes, caffeine, and marijuana/hashish) within the last year, and primary reasons (coping, affiliative, or enhancement) for the use of each drug. Marijuana/hashish users reported lower ASI scores than non-users supporting a negative relation between AS and the use of cannabis. ASI scores were positively correlated with the use of alcohol primarily to cope, and negatively correlated with the use of alcohol primarily to affiliate, among both gender groups, and ASI scores were positively correlated with the use of nicotine primarily to cope among the females. Implications of these findings for understanding risk for abuse of stress-response-dampening drugs by high AS individuals are discussed. PMID:9494951

  9. Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury)

    E-print Network

    Blanchette, Robert A.

    of rodents Disease induction in animal models (e.g. cancer) #12;1. Drug solubilization through engineering of biophysical properties ofp y p p endogenous macromolecules and their transport across the cellular barriers soluble drugs AntiAnti angiogenic therapy for ovarian cancerangiogenic therapy for ovarian cancer

  10. Drugs@FDA: FDA Approved Drug Products

    MedlinePLUS

    ... A to Z Index Follow FDA En Espańol Enter Search terms Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products ... Search by Drug Name, Active Ingredient, or Application Number Enter at least three characters: Advanced Search Browse by ...

  11. Clinically relevant drug interactions with antiepileptic drugs

    PubMed Central

    Perucca, Emilio

    2006-01-01

    Some patients with difficult-to-treat epilepsy benefit from combination therapy with two or more antiepileptic drugs (AEDs). Additionally, virtually all epilepsy patients will receive, at some time in their lives, other medications for the management of associated conditions. In these situations, clinically important drug interactions may occur. Carbamazepine, phenytoin, phenobarbital and primidone induce many cytochrome P450 (CYP) and glucuronyl transferase (GT) enzymes, and can reduce drastically the serum concentration of associated drugs which are substrates of the same enzymes. Examples of agents whose serum levels are decreased markedly by enzyme-inducing AEDs, include lamotrigine, tiagabine, several steroidal drugs, cyclosporin A, oral anticoagulants and many cardiovascular, antineoplastic and psychotropic drugs. Valproic acid is not enzyme inducer, but it may cause clinically relevant drug interactions by inhibiting the metabolism of selected substrates, most notably phenobarbital and lamotrigine. Compared with older generation agents, most of the recently developed AEDs are less likely to induce or inhibit the activity of CYP or GT enzymes. However, they may be a target for metabolically mediated drug interactions, and oxcarbazepine, lamotrigine, felbamate and, at high dosages, topiramate may stimulate the metabolism of oral contraceptive steroids. Levetiracetam, gabapentin and pregabalin have not been reported to cause or be a target for clinically relevant pharmacokinetic drug interactions. Pharmacodynamic interactions involving AEDs have not been well characterized, but their understanding is important for a more rational approach to combination therapy. In particular, neurotoxic effects appear to be more likely with coprescription of AEDs sharing the same primary mechanism of action. PMID:16487217

  12. Immune-Based Drug Shows Potential Against Another Form of Lung Cancer

    MedlinePLUS

    ... reviewed medical journal. SOURCES: New England Journal of Medicine , online, May 31, 2015; Luis Paz-Ares, M.D., Ph.D., professor of medicine, Hospital Universitario 12 de Octubre, Madrid, Spain; Gregory ...

  13. 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

  14. 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

  15. Show morphing of Clinton to Bush General Comments

    E-print Network

    Jacobs, David

    1 Morphing Demo · Show morphing of Clinton to Bush #12;2 General Comments · Morphing is an example, it's widely used. · Morphing provides a good example of the connection between discrete to interpolation position as well as appearance of features. #12;3 Fading · This is morphing with trivial

  16. 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

  17. 20. DOWNSTREAM VIEW OF THE INTAKE STRUCTURE, SHOWING THE SLIDE ...

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

    20. DOWNSTREAM VIEW OF THE INTAKE STRUCTURE, SHOWING THE SLIDE GATES FOR THE CONTROLLED OUTLET, IN POSITION FOR INSTALLATION.... Volume XVII, No. 15, November 13, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  18. 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

  19. [Drugs diverted from reaching drug addicts].

    PubMed

    Poirier, M F; Ginestet, D

    1995-06-01

    To divert from use of psychotropic drugs can take from of a classic toxicomania, sometimes isolated, frequently in association with other toxics: alcohol, opioids. Drugs frequently concerned are anxiolytics: benzodiazepines with a short half-life. Use during more than four months, dependent personality, are risk-factors. Among the other psychotropics, only certain stimulant antidepressants, like amineptine, justify of a particular attention. Drugs of which indication is not psychotropic can induce abuses: more than morphine itself, drugs including opioids or relating are in great demand by drug-addicts: antalgic like dextropropoxyphene or anticough like Neocodion, this one off the prescription. Anorectics, ephedrine vasoconstrictors and beta-stimulants abuse remains frequent. PMID:7659984

  20. Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

    PubMed Central

    Liu, Zhichao; Shi, Qiang; Ding, Don; Kelly, Reagan; Fang, Hong; Tong, Weida

    2011-01-01

    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60–70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the “Rule of Three” was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity. PMID:22194678

  1. Antibiotic resistance in Gram-positive cocci

    Microsoft Academic Search

    J Jeljaszewicz; G Mlynarczyk; A Mlynarczyk

    2000-01-01

    Gram-positive cocci still predominate as a cause of nosocomial- and community-acquired infections. These organisms frequently reveal a high natural, intrinsic resistance to antimicrobials. Additionally, these bacteria are able to acquire resistance to frequently used drugs rapidly through selective pressure of the environment and via the genetic evolution of bacteria. The wide application of antimicrobials in medical and veterinary practice, usage

  2. University of Florida Bee College Honey Show

    E-print Network

    Jawitz, James W.

    University of Florida Bee College Honey Show A REMINDER TO JUDGES 1. Judging will begin promptly or the Honey Show Manager only. 3. The Show will provide color grading glasses if required, towel, basin equipment (see judges checklist). For cake judging, knifes will be provided by the Honey Show Manager. 4

  3. Drug Violations and Aviation Accidents: Findings from the U.S. Mandatory Drug Testing Programs

    PubMed Central

    Li, Guohua; Baker, Susan P.; Zhao, Qi; Brady, Joanne E.; Lang, Barbara H.; Rebok, George W.; DiMaggio, Charles

    2012-01-01

    Aims To assess the role of drug violations in aviation accidents. Design Case-control analysis. Setting Commercial aviation in the United States. Participants Aviation employees who were tested for drugs during 1995 through 2005 under the post-accident testing program (cases, n=4,977) or under the random testing program (controls, n=1,129,922). Measurements Point prevalence of drug violations, odds ratio of accident involvement, and attributable risk in the population. A drug violation was defined as a confirmed positive test for marijuana (? 50 ng/ml), cocaine (? 300 ng/ml), amphetamines (?1000 ng/ml), opiates (? 2000 ng/ml), or phencyclidine (? 25 ng/ml). Findings The prevalence of drug violations was 0.64% [95% confidence interval (CI), 0.62–0.65%] in random drug tests and 1.82% (95% CI, 1.47–2.24%) in post-accident tests. The odds of accident involvement for employees who tested positive for drugs was almost three times the odds for those who tested negative (odds ratio 2.90, 95% CI, 2.35–3.57), with an estimated attributable risk of 1.2%. Marijuana accounted for 67.3% of the illicit drugs detected. The proportion of illicit drugs represented by amphetamines increased progressively during the study period, from 3.4% in 1995 to 10.3% in 2005 (p<0.0001). Conclusions Use of illicit drugs by aviation employees is associated with a significantly increased risk of accident involvement. Due to the very low prevalence, drug violations contribute to only a small fraction of aviation accidents. PMID:21306594

  4. Positive position control of robotic manipulators

    NASA Technical Reports Server (NTRS)

    Baz, A.; Gumusel, L.

    1989-01-01

    The present, simple and accurate position-control algorithm, which is applicable to fast-moving and lightly damped robot arms, is based on the positive position feedback (PPF) strategy and relies solely on position sensors to monitor joint angles of robotic arms to furnish stable position control. The optimized tuned filters, in the form of a set of difference equations, manipulate position signals for robotic system performance. Attention is given to comparisons between this PPF-algorithm controller's experimentally ascertained performance characteristics and those of a conventional proportional controller.

  5. 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.

  6. 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.

  7. 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)

  8. Substance use - prescription drugs

    MedlinePLUS

    ... kinds of drugs that are misused include depressants, opioids, and stimulants. DEPRESSANTS These medicines are also known ... if they try to stop the drug abruptly. OPIOIDS Opioids are powerful painkillers. They are prescribed to ...

  9. 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 Print this page Share this page E-mail ...

  10. 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, ...

  11. 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.

  12. Animal Drug Safety FAQs

    MedlinePLUS

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... Animal & Veterinary Safety & Health Frequently Asked Questions Animal Drug Safety Frequently Asked Questions I gave my dog ...

  13. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  14. Access to Investigational Drugs

    MedlinePLUS

    ... drugs include mechanisms such as an expanded access protocol or a special or compassionate exception. The sponsor ... Expanded Access The purpose of an expanded access protocol is to make investigational drugs that have significant ...

  15. Thrombocytopenia - drug induced

    MedlinePLUS

    ... and a seizure medication called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  16. Information for Consumers (Drugs)

    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 Print this page Share this page E-mail ...

  17. Antifungal Application of Nonantifungal Drugs

    PubMed Central

    Stylianou, Marios; Kulesskiy, Evgeny; Lopes, José Pedro; Granlund, Margareta; Wennerberg, Krister

    2014-01-01

    Candida species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ?150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-Candida activity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against Candida albicans. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active against Candida spp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-Candida activities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different Candida spp., including Candida glabrata. Thus, this screen reveals agents that were previously unknown to be anti-Candida agents, which allows for the design of novel therapies against invasive candidiasis. PMID:24277040

  18. Drug Use History, Drug Test Consequences, and the Perceived Fairness of Organizational Drug Testing Programs

    Microsoft Academic Search

    Donald M. Truxillo; James L. Normandy; Talya N. Bauer

    2001-01-01

    We explored the effects of drug use history (current\\/recent user of drugs, used\\/tried drugs, never tried drugs) and a measure of drug test consequences (termination versus rehabilitation) on the perceived fairness of organizational drug testing (DT). Data were collected as part of a statewide telephone survey of the general adult population. Personal drug use history and DT consequences interacted such

  19. Rethinking drug policy: an integrity preserving compromise position

    E-print Network

    Crispino, Azzurra

    2006-10-30

    the chronically runny nose. Sniffing and dilated pupils are the most recognized signs of a cocaine user. Chronic cocaine use can lead to paranoia and formication, a phenomenon wherein the user believes there are ants crawling under her skin, which can lead... difference between PCP and LSD, and its biggest danger, is that PCP ?can result in mood disorders, acute anxiety, paranoia and violent behavior,? and can also substantially increase the strength of the user, creating an artificially strong and violent...

  20. Drug Abuse Resistance

    NSDL National Science Digital Library

    Mrs. Koyle

    2005-03-22

    STUDENTS NEED TO BE AWARE OF THE DANGERS OF DRUGS! The following includes helpful ways to learn about drug abuse resistance. Please finish the smoking quiz for class discussion on Friday! If parents would like a helpful resource on how to teach their children to say no to drugs and alcohol. See NIDA for Teens : The Science Behind Drug Abuse Click on the following link ...

  1. Drug Testing in Hair

    Microsoft Academic Search

    Pascal Kintz

    Given the limitations of self-reports on drug use, testing for drugs-of-abuse is important for most clinical and forensic\\u000a toxicological situations, both for assessing the reality of the intoxication and for evaluation of the level of drug impairment.\\u000a It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use.\\u000a The presence of

  2. DrugDigest

    NSDL National Science Digital Library

    DrugDigest is a "noncommercial, evidence-based, consumer health and drug information site dedicated to empowering consumers to make informed choices about drugs and treatment options." This exhaustive Web site offers a variety of resources to help readers manage their health, including easy-to-read reference materials, a potentially life-saving drug interactions database, informative news and features, and eBulletins -- an email service that delivers news and information on selected health conditions, free of charge.

  3. Characterization of serotonin transporter gene (SLC6A4) polymorphisms and its association with drug dependence in a Jordanian Arab population.

    PubMed

    Al-Eitan, Laith Naser; Jaradat, Saied Ali; Qin, Wenwen; Wildenauer, Diah Mutiara B; Wildenauer, Dieter D B; Hulse, Gary K; Tay, Guan K

    2014-08-01

    Drug dependence is a pattern of repeated self-administration of a drug, which can result in tolerance, withdrawal and compulsive drug-taking behaviour. It has been recently suggested that 5-HTTLPR (LL/LS/SS) variants and rs25531 (A/G) polymorphism in the serotonin transporter gene (SLC6A4) may play a role in drug dependence. The current study aimed to (1) identify allelic, haplotypic and genotypic frequencies of the 5-HTTLPR variants and rs25531 polymorphisms of SLC6A4 gene in drug and nondrug-dependent Jordanian Arab population and (2) determine whether there is an association of these variants in a drug-dependent population from the same area. Jordanian drug male addicts of Arab descent (n = 192) meeting the Diagnostic and Statistical Manual of Mental Disorders - Fourth edition criteria for drug dependence and 230 healthy male controls from an ethnically homogenous Jordanian Arab population were examined. Genotyping was performed using the restriction fragment length polymorphism-polymerase chain reaction-based method to genotype the 5-HTTLPR variants and detect the A/G polymorphism at position rs25531. The biallelic analysis revealed that the frequency of 5-HTTLPR (LL/LS/SS) genotypes was statistically significant different between drug-dependent individuals and controls (? (2) (2, N = 422), p = 0.04). Drug-dependent subjects had a higher frequency of 'L' allele. However, using the triallelic approach, the estimated frequency of haplotypes (SA , SG , LA and LG ) and phased genotypes (LA /LA , LA /SA , LA /LG , SA /SA and SA /SG) did not show significant association with drug dependence (? (2) (3, N = 422), p = 0.53 and ? (2) (4, N = 422), p = 0.06, respectively). This study suggests a putative role of the 5-HTTLPR for drug dependence in the Jordanian Nationals of Arab ancestry. PMID:23033208

  4. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    NASA Astrophysics Data System (ADS)

    Hamlekhan, Azhang; Sinha-Ray, Suman; Takoudis, Christos; Mathew, Mathew T.; Sukotjo, Cortino; Yarin, Alexander L.; Shokuhfar, Tolou

    2015-06-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT.

  5. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

    PubMed

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raśl J

    2014-04-27

    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

  6. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease

    PubMed Central

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raśl 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

  7. Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis

    PubMed Central

    Borrell, Sņnia; Teo, Youjin; Giardina, Federica; Streicher, Elizabeth M.; Klopper, Marisa; Feldmann, Julia; Müller, Borna; Victor, Tommie C.; Gagneux, Sebastien

    2013-01-01

    Background and objectives: Multidrug resistant (MDR) bacteria are a growing threat to global health. Studies focusing on single antibiotics have shown that drug resistance is often associated with a fitness cost in the absence of drug. However, little is known about the fitness cost associated with resistance to multiple antibiotics. Methodology: We used Mycobacterium smegmatis as a model for human tuberculosis (TB) and an in vitro competitive fitness assay to explore the combined fitness effects and interaction between mutations conferring resistance to rifampicin (RIF) and ofloxacin (OFX); two of the most important first- and second-line anti-TB drugs, respectively. Results: We found that 4 out of 17 M. smegmatis mutants (24%) resistant to RIF and OFX showed a statistically significantly higher or lower competitive fitness than expected when assuming a multiplicative model of fitness effects of each individual mutation. Moreover, 6 out of the 17 double drug-resistant mutants (35%) had a significantly higher fitness than at least one of the corresponding single drug-resistant mutants. The particular combinations of resistance mutations associated with no fitness deficit in M. smegmatis were the most frequent among 151 clinical isolates of MDR and extensively drug-resistant (XDR) Mycobacterium tuberculosis from South Africa. Conclusions and implications: Our results suggest that epistasis between drug resistance mutations in mycobacteria can lead to MDR strains with no fitness deficit, and that these strains are positively selected in settings with a high burden of drug-resistant TB. Taken together, our findings support a role for epistasis in the evolution and epidemiology of MDR- and XDR-TB. PMID:24481187

  8. 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… ...

  9. 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…

  10. 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…

  11. Nanosuspensions in drug delivery

    Microsoft Academic Search

    Barrett E. Rabinow

    2004-01-01

    A surprisingly large proportion of new drug candidates emerging from drug discovery programmes are water insoluble, and therefore poorly bioavailable, leading to abandoned development efforts. These so-called 'brickdust' candidates can now be rescued by formulating them into crystalline nanosuspensions. In the process of overcoming issues involving solubility, additional pharmacokinetic benefits of the drugs so formulated have come to be appreciated.

  12. A Thermally Activated Drug

    E-print Network

    Paris-Sud XI, Université de

    to collapse. Candidate cooling mechanisms based on endothermic chemical reac- tions, the Peltier effectA Thermally Activated Drug Delivery System Based on a Thermoresponsive Polymer and a Cooling Device implanted drug delivery system. The deliv- ery device consists of a cooling material coated by a drug

  13. A Drug Education Program.

    ERIC Educational Resources Information Center

    Chapel Hill City Schools, NC.

    GRADES OR AGES: K-12. SUBJECT MATTER: Drug education. ORGANIZATION AND PHYSICAL APPEARANCE: The introductory material includes objectives, a discussion of drugs as a community problem, suggestions for teaching about drugs, and the teaching of values. The program content is divided into primary grades, grade four, grade five, grade six, the middle…

  14. Educating against Drug Abuse.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This book is a compilation of drug education and drug abuse prevention materials collected by United Nations Educational, Scientific and Cultural Organization (UNESCO) along with example of activities carried out by various countries. It opens with four introductory papers by separate authors: (1) "Prevention of Drug Dependence: A Utopian Dream?"…

  15. Employee Drug Testing

    Microsoft Academic Search

    Charles Neuhaus Jr; Richard Caplan

    1992-01-01

    The authors examine the limitations of employee drug testing as a method of improving productivity and safety in the workplace. Attempts to modify licit and illicit drug use, including prohibition, are briefly reviewed, and the importance of social setting is underscored. The authors discourage the widespread use of employee drug testing because of problems in interpreting the significance of test

  16. 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.

  17. Drugs and the Coach.

    ERIC Educational Resources Information Center

    Clarke, Kenneth S., Ed.

    This volume is based on the premise that professional preparation for coaching should include viable experiences in drug education, with particular reference to coping with drug-related problems. The first section provides general information on the purposes and effects of drugs, controls, and concepts of doping. The second section deals with four…

  18. Drug Free Campus Statement.

    ERIC Educational Resources Information Center

    Casper Coll., WY.

    These three brief documents, a policy statement, a summary of pertinent laws on alcohol and illegal drugs, and a substance addiction specialist curriculum description, taken together describe the Casper College (Wyoming) drug and alcohol abuse prevention program. The policy statement briefly summarizes the health risks associated with drug and…

  19. National Drug Control Strategy.

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, Washington, DC.

    This report presents a comprehensive blueprint for new direction and effort in the national fight against illegal drug use. It is the result of an intensive review of federal anti-drug efforts to date and incorporates advice and recommendations from hundreds of interested and involved anti-drug leaders outside the federal government. The…

  20. Inferring cuisine--drug interactions using the linked data approach.

    PubMed

    Jovanovik, Milos; Bogojeska, Aleksandra; Trajanov, Dimitar; Kocarev, Ljupco

    2015-01-01

    Food - drug interactions are well studied, however much less is known about cuisine - drug interactions. Non-native cuisines are becoming increasingly more popular as they are available in (almost) all regions in the world. Here we address the problem of how known negative food - drug interactions are spread in different cuisines. We show that different drug categories have different distribution of the negative effects in different parts of the world. The effects certain ingredients have on different drug categories and in different cuisines are also analyzed. This analysis is aimed towards stressing out the importance of cuisine - drug interactions for patients which are being administered drugs with known negative food interactions. A patient being under a treatment with one such drug should be advised not only about the possible negative food - drug interactions, but also about the cuisines that could be avoided from the patient's diet. PMID:25792182

  1. Inferring Cuisine - Drug Interactions Using the Linked Data Approach

    PubMed Central

    Jovanovik, Milos; Bogojeska, Aleksandra; Trajanov, Dimitar; Kocarev, Ljupco

    2015-01-01

    Food - drug interactions are well studied, however much less is known about cuisine - drug interactions. Non-native cuisines are becoming increasingly more popular as they are available in (almost) all regions in the world. Here we address the problem of how known negative food - drug interactions are spread in different cuisines. We show that different drug categories have different distribution of the negative effects in different parts of the world. The effects certain ingredients have on different drug categories and in different cuisines are also analyzed. This analysis is aimed towards stressing out the importance of cuisine - drug interactions for patients which are being administered drugs with known negative food interactions. A patient being under a treatment with one such drug should be advised not only about the possible negative food - drug interactions, but also about the cuisines that could be avoided from the patient's diet. PMID:25792182

  2. Biodegradable fibre scaffolds incorporating water-soluble drugs and proteins.

    PubMed

    Ma, J; Meng, J; Simonet, M; Stingelin, N; Peijs, T; Sukhorukov, G B

    2015-07-01

    A new type of biodegradable drug-loaded fibre scaffold has been successfully produced for the benefit of water-soluble drugs and proteins. Model drug loaded calcium carbonate (CaCO3) microparticles incorporated into poly(lactic acid-co-glycolic acid) (PLGA) fibres were manufactured by co-precipitation of CaCO3 and the drug molecules, followed by electrospinning of a suspension of such drug-loaded microparticles in a PLGA solution. Rhodamine 6G and bovine serum albumin were used as model drugs for our release study, representing small bioactive molecules and protein, respectively. A bead and string structure of fibres was achieved. The drug release was investigated with different drug loadings and in different pH release mediums. Results showed that a slow and sustained drug release was achieved in 40 days and the CaCO3 microparticles used as the second barrier restrained the initial burst release. PMID:26155976

  3. POSITION DESCRIPTION POSITION TITLE: Research Assistant

    E-print Network

    McCormack, Jon

    POSITION DESCRIPTION POSITION TITLE: Research Assistant POSITION NUMBER: DEPARTMENT/UNIT: Clayton and sound arts. KEY RESULTS AREAS AND RESPONSIBILITIES The Research Assistant will be expected, the Research Assistant's duties will be focussed on developmental modelling, ecosystem modelling, and on new

  4. Prevalence of drug use in commercial tractor-trailer drivers.

    PubMed

    Couper, Fiona J; Pemberton, Melissa; Jarvis, Anjanette; Hughes, Marty; Logan, Barry K

    2002-05-01

    An enforcement emphasis project, "Operation Trucker Check," was established in order to determine the extent to which commercial tractor-trailer drivers were operating their vehicles while impaired by drugs. A total of 1079 drivers and their vehicles were assessed for driver and equipment violations, and drivers additionally underwent preliminary field sobriety tests conducted by drug recognition expert (DRE) officers. Anonymous urine specimens for drug analysis were requested, and 822 urine specimens were obtained in total. Compliance with the drug-testing portion was voluntary, and there was a 19% refusal rate. Overall, 21% of the urine specimens tested positive for either illicit, prescription, and/or over-the-counter drugs, and 7% tested positive for more than one drug. Excluding caffeine and nicotine, the largest number of positive findings (9.5%) were for CNS stimulants, such as methamphetamine, amphetamine, phentermine, ephedrine/pseudoephedrine, and cocaine. The second most frequently encountered drug class were the cannabinoids, with 4.3% of drivers testing positive for marijuana metabolites. Only 11 drivers (1.3%) were positive for alcohol. Sixteen truck drivers (1.6%) were charged with driving under the influence of drugs after a full DRE evaluation was conducted. The results indicate that in spite of comprehensive drug testing in the trucking industry, some tractor-trailer drivers are continuing to take illicit and other drugs with the potential of having a negative effect on their driving ability. On the other hand, only a few drivers were, in fact, deemed to be under the influence of drugs at the time of driving when evaluated by DRE officers. PMID:12051337

  5. New Hampshire Guide 4-H Dog Shows

    E-print Network

    New Hampshire, University of

    New Hampshire Guide to 4-H Dog Shows UNH Cooperative Extension 4-H Youth Development Moiles House cooperating. #12;NH Guide to 4-H Dog Shows i Table of Contents INTRODUCTION .................................................................................................................................2 Purpose of the 4-H Dog Project

  6. Flat Globe: Showing the Changing Seasons

    NSDL National Science Digital Library

    Jesse Allen

    1998-09-09

    SeaWiFS false color data showing seasonal change in the oceans and on land for the entire globe. The data is seasonally averaged, and shows the sequence: fall, winter, spring, summer, fall, winter, spring (for the Northern Hemisphere).

  7. For Some Breast Cancers, New Drug May Be Treatment Option

    Cancer.gov

    Results from an international clinical trial suggest that women with metastatic, HER2-positive breast cancer that is no longer responding to the targeted therapy trastuzumab (Herceptin) may soon have a new treatment option. Women who received the investigational drug trastuzumab emtansine (T-DM1) lived more than 3 months longer without their tumors progressing than women who received the chemotherapy drug capecitabine (Xeloda) and the targeted drug lapatinib (Tykerb).

  8. Mussel-inspired protein-mediated surface functionalization of electrospun nanofibers for pH-responsive drug delivery.

    PubMed

    Jiang, J; Xie, J; Ma, B; Bartlett, D E; Xu, A; Wang, C-H

    2014-03-01

    pH-responsive drug delivery systems could mediate drug releasing rate by changing the pH values at specific times as per the pathophysiological need of the disease. This paper demonstrates that a mussel-inspired protein polydopamine coating can tune the loading and releasing rate of charged molecules from electrospun poly(?-caprolactone) (PCL) nanofibers in solutions with different pH values. In vitro release profiles show that the positive charged molecules release significantly faster in acidic than those in neutral and basic environments within the same incubation time. The results of fluorescein diacetate staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays show the viability of cancer cells after treatment with doxorubicin-released media at different pH values qualitatively and quantitatively, indicating that the media containing doxorubicin that were released in solutions at low pH values could kill a significantly higher number of cells than those released in solutions at high pH values. Together, the pH-responsive drug delivery systems based on polydopamine-coated PCL nanofibers could have potential application in the oral delivery of anticancer drugs for treating gastric cancer and in vaginal delivery of anti-viral drugs or anti-inflammatory drugs, which could raise their efficacy, deliver them to the specific target and minimize their toxic side effects. PMID:24287161

  9. Mussel inspired protein-mediated surface functionalization of electrospun nanofibers for pH-responsive drug delivery

    PubMed Central

    Jiang, Jiang; Xie, Jingwei; Ma, Bing; Bartlett, David E.; Xu, An; Wang, Chi-Hwa

    2014-01-01

    pH-responsive drug delivery systems could mediate drug releasing rate by changing pH values at specific time as per the pathophysiological need of the disease. Herein, we demonstrated a mussel inspired protein polydopamine coating can tune the loading and releasing rate of charged molecules from electrospun poly (?-caprolactone) (PCL) nanofibers in solutions with different pH values. In vitro release profiles showed that the positive charged molecules released significantly faster in acidic than those in neutral and basic environments within the same incubation time. The results of fluorescein diacetate staining and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed the viability of cancer cells after treatment with doxorubicin released media at different pH values qualitatively and quantitatively, indicating the media contained doxorubicin which was released in solutions at low pH values could kill significantly higher number of cells than that released in solutions at high pH values. Together, the pH-responsive drug delivery systems based on polydopamine-coated PCL nanofibers could have potential applications in oral delivery of anticancer drugs for treating gastric cancer and vaginal delivery of anti-viral drugs or anti-inflammatory drugs, which could raise their efficacy, deliver them to the specific target, and minimize their toxic side effects. PMID:24287161

  10. Detectability of new psychoactive substances, 'legal highs', in CEDIA, EMIT, and KIMS immunochemical screening assays for drugs of abuse.

    PubMed

    Beck, Olof; Rausberg, Linnea; Al-Saffar, Yasir; Villen, Tomas; Karlsson, Lennart; Hansson, Therese; Helander, Anders

    2014-05-01

    The increasing number of new psychoactive substances made available for recreational drug use has created a challenge for clinical toxicology and drug testing laboratories. As a consequence, the routine immunoassay drug testing may become less effective due to an increased occurrence of false negative and false positive screening results. This work aimed to extend the knowledge about analytical cross-reactivity of new substances in selected CEDIA, EMIT, and KIMS immunoassays for drugs-of-abuse screening. Urine standards were prepared by spiking blank urine with 45 new substances. Authentic urine samples from intoxication cases identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were also studied. Several new psychoactive substances were demonstrated to display cross-reactivity in the immunoassays. CEDIA Amphetamine/Ecstasy and EMIT d.a.u. Amphetamine Class tests showed the highest reactivity towards the new drugs, which was expected since many have amphetamine-like structure and activity. In the samples from authentic cases, five new substances displayed 100% detection rate in the CEDIA Amphetamine/Ecstasy test. In conclusion, cross-reactivity data in routine urine drug screening immunoassays for a number of new psychoactive substances not studied before were reported. In both spiked and authentic urine samples, some new substances showed significant cross-reactivity and are thus detectable in the routine screening methods. PMID:24665024

  11. Fluorescent graphene oxide via polymer grafting: an efficient nanocarrier for both hydrophilic and hydrophobic drugs.

    PubMed

    Kundu, Aniruddha; Nandi, Sudipta; Das, Pradip; Nandi, Arun K

    2015-02-18

    Functionalized graphene-based drug delivery vehicles have conquered a significant position because functionalization improves its biocompatibility and stability in cell medium, leaving sufficient graphitic basal plane for drug loading through ?-? stacking. In this study, poly(N-isopropylacrylamide) (PNIPAM) is covalently grafted from the surface of graphene oxide (GO) via a facile, eco-friendly and an easy procedure of free radical polymerization (FRP) using ammonium persulfate initiator. Various spectroscopic and microscopic studies confirm the successful grafting of PNIPAM from GO surface. PNIPAM-grafted GO (GPNM) exhibits enhanced thermal stability, improved dispersibility both in aqueous and cell medium, and better biocompatibility and cell viability compared to GO. Interestingly, GPNM displays an exciting fluorescence property in aqueous medium, which is a hike of intensity at 36 °C due to the lower critical solution temperature (LCST) of PNIPAM chains (32 °C). Moreover both hydrophilic (doxorubicin (DOX)) and hydrophobic (indomethacin (IMC)) drugs loaded on the surface of GPNM hybrid exhibits its efficacy as an efficient carrier for both types of drugs. Cellular uptakes of free DOX and DOX-loaded GPNM (GPNM-DOX) are evidenced both from optical and fluorescence imaging of live cells, and the efficiency of drug is significantly improved in the loaded system. The release of DOX from GPNM-DOX was achieved at pH 4, relevant to the environment of cancer cells. The pH-triggered release of hydrophobic drug was also studied using UV-vis spectroscopy via alginate encapsulation, showing a great enhancement at pH = 7.4. The IMC is also found to be released by human serum albumin using dialysis technique. The GPNM nanomaterial shows the property of simultaneous loading of DOX and IMC as well as pH-triggered simultaneous release of both of the drugs. PMID:25612470

  12. Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs

    E-print Network

    Barthelat, Francois

    Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs 1gauthier@emt.inrs.ca #12;Why macromolecules in drug delivery? 2gauthier@emt.inrs.ca Classic chemotherapy Drug delivery? Targeting A carrier for small drugs A release mechanism (if necessary) Protection of drug cargo #12;How? 3

  13. Inside Gun Shows What Goes On

    E-print Network

    Leistikow, Bruce N.

    Inside Gun Shows What Goes On When Everybody Thinks Nobody's Watching Epilogue #12;Inside Gun Shows;Epilogue In February 2010, I attended a Crossroads of the West gun show at the Arizona State Fairgrounds here an update on each of the Phoenix obser- vations made in the photo-essay portion of Inside Gun

  14. Inside Gun Shows What Goes On

    E-print Network

    Leistikow, Bruce N.

    Preface Inside Gun Shows What Goes On When Everybody Thinks Nobody's Watching #12;#12;Inside Gun-Violence Effort. She put gun shows on my radar and is an ace straw-purchase spotter. Thanks also to Barbara Claire a great public institution. He was right. #12;Contents Preface Executive Summary Gun Shows in Context How

  15. Inside Gun Shows What Goes On

    E-print Network

    Nguyen, Danh

    Inside Gun Shows What Goes On When Everybody Thinks Nobody's Watching Executive Summary #12;Inside Gun Shows What Goes on When Everybody Thinks Nobody's Watching Garen Wintemute, MD, MPH Violence;Executive Summary Gun shows are surrounded by controversy. On the one hand, they are important economic

  16. Pharmacogenetics and Pharmacogenomics II: Genetic Determinants of Drug Responses and Adverse Drug Reactions

    Microsoft Academic Search

    Stephane Dalle; Sandra Knowles; Neil H. Shear

    \\u000a The ability to predict efficacy and safety is crucial for drug discovery and development. To date, there are only a few genetic\\u000a biomarkers whose clinical validity in predicting drug response has been clearly established; for example, HER-2\\/neu-positivity\\u000a in breast cancer as a predictor of response to trastuzumab (Herceptin) [1]. Patient variability in response to medications\\u000a can range from failure to

  17. Progressive cellular immune impairment leading to development of AIDS: two-year prospective study of HIV infection in drug addicts.

    PubMed Central

    Fernandez-Cruz, E; Fernandez, A M; Gutierrez, C; Garcia-Montes, M; de la Morena, M T; Rodriguez-Villanueva, J; Longo, N; Zabay, J M

    1988-01-01

    We have studied immunological, serological and clinical abnormalities in 264 HIV-positive and HIV-negative drug abusers. Ninety percent of the 264 drug addicts (mean age 26 +/- 0.8 years) were found to have HIV antibodies and there was a significant increase (P less than 0.01) in the frequency of HIV antibody positivity with increasing duration of exposure to parenteral drug abuse. There was a very strong correlation between the progressive decline of the mean T4+ helper/inducer cells and T4+/T8+ ratio, the low response to pokeweed mitogen and the more severe clinical manifestations of HIV infection. Impairment of delayed-type hypersensitivity reaction to recall antigens was only seen in group IV as defined by the Center for Disease Control. Within group IV, anergy was found to be highly associated (83%) in patients with opportunistic infections. All other HIV-positive addicts from groups II and III, as well as HIV-negative addicts had normal in vivo responses to test antigens. We have also analysed in a prospective follow-up lasting 6-24 months, the evolution of HIV infection in a cohort of 50 HIV-antibody-positive drug addicts. Thirty-two percent showed clinical progression and most of the drug addicts that proceeded to full-blown AIDS developed anergy (82%) prior to clinical deterioration with development of opportunistic infections. We conclude, that in seropositive drug addicts a low absolute count of helper/inducer cells (mean +/- s.e. = 243 +/- 48 cells/mm3), a low response to pokeweed mitogen and anergy are predictive markers of progression to AIDS. PMID:3261660

  18. Drug-induced phospholipidosis.

    PubMed

    Anderson, Nora; Borlak, Jürgen

    2006-10-01

    Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. Organs affected by phospholipidosis exhibit inflammatory reactions and histopathological changes. Despite significant advances in the understanding of drug-altered lipid metabolism, the relationship between impaired phospholipid metabolism and drug-induced toxicity remains enigmatic. Here we review molecular features of inheritable lysosomal storage disorders as a molecular mimicry of drug-induced phospholipidosis for an improved understanding of adverse drug reaction. PMID:16979167

  19. Drug metabolism in microorganisms.

    PubMed

    Murphy, Cormac D

    2015-01-01

    Several wild type and recombinant microorganisms can transform drugs to the equivalent human metabolites. Fungi, such as Cunninghamella spp., and Streptomyces bacteria express cytochrome P450 (CYP) enzymes that enable analogous phase I (oxidative) reactions with a wide range of drugs. The gene encoding the bifunctional CYP102A1 in Bacillus megaterium can be expressed easily in E. coli, and extensive mutagenesis experiments have generated numerous variants that can produce human drug metabolites. Additionally, human CYP isoforms have been expressed in various hosts. The application of microbial CYPs to the production of human drug metabolites is reviewed, and additional applications in the field of drug development are considered. PMID:25179825

  20. Drug-induced sensorineural deafness caused by antithyroid drugs: a rare side effect.

    PubMed

    Raja, U Y; Kumar, A; Possamai, V; Warner, D; Barton, D

    2010-09-01

    Acute ototoxicity is a rare but important complication of antithyroid drugs. Although previous cases have been reported in the medical literature, these cases occurred in younger patients with serological evidence of lupus-like syndrome with positive antidouble-stranded deoxyribonucleic acid and antineutrophil cytoplasmic antibodies. We describe the case of a 68-year-old Caucasian male who developed deafness and tinnitus one week after being prescribed carbimazole. The management options include stopping the culprit drug, treatment with immunosuppressive drugs and referring the patient for urgent thyroidectomy. Healthcare professionals who prescribe antithyroid drugs should be aware of this rare but potentially serious complication, so that early drug withdrawal and referral for surgery can be considered. PMID:21127764

  1. DEA Multimedia Drug Library: Marijuana

    MedlinePLUS

    ... OPERATIONS Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip DRUG INFO Drug Fact Sheets ... Operations Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip Drug Info Drug Fact Sheets ...

  2. Trends in Prescription Drug Abuse

    MedlinePLUS

    ... HIV/AIDS Medical Consequences Mental Health Pain Prevention Substance Abuse in Military Life Treatment Trends & Statistics Publications Funding ... Drug Abuse » Trends in prescription drug abuse Prescription Drug Abuse Email Facebook Twitter Trends in prescription drug abuse ...

  3. Drugs Approved for Esophageal Cancer

    Cancer.gov

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

  4. Drugs Approved for Skin Cancer

    Cancer.gov

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

  5. How to Read Drug Labels

    MedlinePLUS

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  6. Drugs Approved for Liver Cancer

    Cancer.gov

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

  7. Drugs Approved for Vulvar Cancer

    Cancer.gov

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

  8. Drugs Approved for Kaposi Sarcoma

    Cancer.gov

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

  9. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

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

  10. Drugs Approved for Endometrial Cancer

    Cancer.gov

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

  11. Drugs Approved for Bone Cancer

    Cancer.gov

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

  12. Drugs Approved for Penile Cancer

    Cancer.gov

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

  13. Drugs Approved for Vaginal Cancer

    Cancer.gov

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

  14. Drug Use Forecasting in 1992.

    ERIC Educational Resources Information Center

    National Institute of Justice Journal, 1993

    1993-01-01

    Presents results from the 1992 Drug Use Forecasting (DUF) program that measures illicit drug use among persons arrested for criminal behavior. Adult use of specific drugs, male juvenile drug use, and the role of the DUF are explored. (GLR)

  15. Medical Consequences of Drug Abuse

    MedlinePLUS

    ... Home » Related Topics » Medical Consequences Medical Consequences of Drug Abuse Email Facebook Twitter Drug addiction is a brain ... and lung disease can all be affected by drug abuse. Some of these effects occur when drugs are ...

  16. Orphanet Berichtsreihe Orphan Drugs Datenerhebung

    E-print Network

    Manstein, Dietmar J.

    Orphanet Berichtsreihe Orphan Drugs Datenerhebung Verzeichnis der in Europa zugelassenen Orphan Drugs Mit europäischer Orphan-Drug-Designation und europäischer Marktzulassung* Mit europäischer Marktzulassung* ohne vorherige Orphan-Drug-Designation *Zentrales Zulassungsverfahren der Europäischen

  17. Positive basis for surface skein algebras.

    PubMed

    Thurston, Dylan Paul

    2014-07-01

    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

  18. Prevalence of psychoactive substances, alcohol, illicit drugs, and medicines, in Spanish drivers: a roadside study.

    PubMed

    Gómez-Talegón, Trinidad; Fierro, Inmaculada; Gonzįlez-Luque, Juan Carlos; Colįs, Monica; López-Rivadulla, Manuel; Javier Įlvarez, F

    2012-11-30

    Following population, geographic, road type and time criteria, Spain has carried out random, roadside controls of 3302 representative sample of Spanish drivers, including saliva analysis for 24 psychoactive substances and alcohol breath tests. The 81.4% of the drivers were male, with an average age of 34.8±11.8 (mean±SD). The 17% of the drivers were found to be positive to any of the substances analysed. The 6.6% of the drivers found positive to alcohol (>0.05 mg/l in breath), 11% were found positive to any illicit drug, and 2% were positive to one of the medicines analysed. Some drivers were positive in more than one substance. The most common illicit drugs among Spanish drivers were cannabis (7.7%), or cocaine (3.5%), either alone or combined with other substances. The most prevalent medicines were the benzodiazepines (1.6%). As a tendency, higher figures for positive cases were observed among males than in females (being statistically significant the differences for alcohol, cannabis and cocaine). Alcohol and cocaine positive cases were more frequently found among drivers of urban roads. Alcohol positive cases (alone, >0.05 mg/l), were more likely found as age increase (OR=1.02), those driving in urban roads (OR=2.13), and driving at any period than weekdays, while alcohol+drugs cases were more likely found among males (OR=2.819), those driving on urban road (OR=2.17) and driving at night periods. Finding a medicines positive case was more likely as elder the driver was (OR=1.05). There have been differences in the prevalence of positive cases of alcohol, cannabis and cocaine, in relation to the period of the week: in three cases the highest prevalence seen in night time. This study shows the high prevalence of psychoactive substances and alcohol in Spanish drivers, mainly illicit drugs (cannabis). This question requires a response from the authorities and from society, with an integral and multi-disciplinary approach that can heighten the population's awareness of the risks of driving under the influence of certain substances. PMID:22947432

  19. Testing Drugs Versus Testing For Drug Use: Private Risk Management in the Shadow of the Criminal Law

    E-print Network

    MacCoun, Robert J.

    2007-01-01

    analysis found no measurable association between either random or “for cause” drug testinganalysis adding the 2002 data, see Ryoko Yamaguchi et al. , Drug TestingDrug Awareness, early 1970s Table 2 shows data from the national testing program of PharmChem’s Analysis

  20. Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery

    PubMed Central

    Sim, E; Abuhammad, A; Ryan, A

    2014-01-01

    Arylamine N-acetyltransferases (NATs) are polymorphic drug-metabolizing enzymes, acetylating arylamine carcinogens and drugs including hydralazine and sulphonamides. The slow NAT phenotype increases susceptibility to hydralazine and isoniazid toxicity and to occupational bladder cancer. The two polymorphic human NAT loci show linkage disequilibrium. All mammalian Nat genes have an intronless open reading frame and non-coding exons. The human gene products NAT1 and NAT2 have distinct substrate specificities: NAT2 acetylates hydralazine and human NAT1 acetylates p-aminosalicylate (p-AS) and the folate catabolite para-aminobenzoylglutamate (p-abaglu). Human NAT2 is mainly in liver and gut. Human NAT1 and its murine homologue are in many adult tissues and in early embryos. Human NAT1 is strongly expressed in oestrogen receptor-positive breast cancer and may contribute to folate and acetyl CoA homeostasis. NAT enzymes act through a catalytic triad of Cys, His and Asp with the architecture of the active site-modulating specificity. Polymorphisms may cause unfolded protein. The C-terminus helps bind acetyl CoA and differs among NATs including prokaryotic homologues. NAT in Salmonella typhimurium supports carcinogen activation and NAT in mycobacteria metabolizes isoniazid with polymorphism a minor factor in isoniazid resistance. Importantly, nat is in a gene cluster essential for Mycobacterium tuberculosis survival inside macrophages. NAT inhibitors are a starting point for novel anti-tuberculosis drugs. Human NAT1-specific inhibitors may act in biomarker detection in breast cancer and in cancer therapy. NAT inhibitors for co-administration with 5-aminosalicylate (5-AS) in inflammatory bowel disease has prompted ongoing investigations of azoreductases in gut bacteria which release 5-AS from prodrugs including balsalazide. PMID:24467436