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Sample records for drug sensitivity testing

  1. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes

    Science.gov (United States)

    Canetti, G.; Fox, Wallace; Khomenko, A.; Mahler, H. T.; Menon, N. K.; Mitchison, D. A.; Rist, N.; Šmelev, N. A.

    1969-01-01

    In a paper arising out of an informal international consultation of specialists in the bacteriology of tuberculosis held in 1961, an attempt was made to formulate criteria, and specify technical procedures, for reliable tests of sensitivity (the absolute-concentration method, the resistance-ratio method and the proportion method) to the 3 main antituberculosis drugs (isoniazid, streptomycin and p-aminosalicylic acid). Seven years later, a further consultation was held to review the latest developments in the field and to suggest how sensitivity tests might be put to practical use in tuberculosis control programmes. The participants reached agreement on how to define drug sensitivity and resistance, and stressed the importance of using a discrimination approach to the calibration of sensitivity tests. Their views are contained in the present paper, which also includes descriptions of the sensitivity tests used by the Medical Research Council of Great Britain for first- and second-line drugs (minimal inhibitory concentration and resistance-ratio methods), the two main variants of the proportion method developed by the Institut Pasteur, Paris, and a method for calibrating sensitivity tests. PMID:5309084

  2. Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

    Science.gov (United States)

    Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmäki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A

    2017-08-22

    Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.

  3. Evaluation of 5-fluorouracil applicability by multi-point collagen gel droplet embedded drug sensitivity test.

    Science.gov (United States)

    Ochiai, Takumi; Nishimura, Kazuhiko; Noguchi, Hajime; Kitajima, Masayuki; Tsuruoka, Yuko; Takahashi, Yuka

    2005-07-01

    The drug sensitivity of tumor cells is one of key issues to explore individualized therapy for cancer patients. One of such methods is in vitro anticancer drug sensitivity test which is generally based on one drug concentration and contact time. In this study, 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer patients was evaluated by collagen gel droplet embedded drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Cancer cells from 19 patients were measured for 9 drug concentration/contact time conditions (cohort 1) and from 34 patients were measured for 2 drug concentration/contact time conditions (cohort 2) using CD-DST. There was not significant difference in growth inhibition rate for 1.0 microg/ml for 24 h and 0.2 microg/ml for 120 h, which gives the same area under the curve (AUC) (p=0.832) in all 53 patients (cohort 1 and 2). In cohort 1, 9 conditions were successfully measured in 18 of 19 cohort 1 patients (94.7%). The drug concentrations and growth inhibition rate approximated to logarithmic curve for all 3 contact times and 50% inhibitory concentration (IC50) values at 3 contact times could be calculated in these 18 patients. Growth inhibition rate and AUC also approximated to logarithmic curve. These values varied several orders of magnitude among patients. In vitro antitumor effect of 5-FU depended on AUC in colorectal tumor and it might support the use of continuous infusion or oral therapy which generates significant AUC with manageable toxicity. Some patients demonstrating low 5-FU sensitivity could not be indicated for 5-FU based therapy, and non-5-FU therapy should be explored for them.

  4. Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.

    Science.gov (United States)

    Andersson, E I; Pützer, S; Yadav, B; Dufva, O; Khan, S; He, L; Sellner, L; Schrader, A; Crispatzu, G; Oleś, M; Zhang, H; Adnan-Awad, S; Lagström, S; Bellanger, D; Mpindi, J P; Eldfors, S; Pemovska, T; Pietarinen, P; Lauhio, A; Tomska, K; Cuesta-Mateos, C; Faber, E; Koschmieder, S; Brümmendorf, T H; Kytölä, S; Savolainen, E-R; Siitonen, T; Ellonen, P; Kallioniemi, O; Wennerberg, K; Ding, W; Stern, M-H; Huber, W; Anders, S; Tang, J; Aittokallio, T; Zenz, T; Herling, M; Mustjoki, S

    2017-08-14

    T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clinical testing.Leukemia advance online publication, 1 September 2017; doi:10.1038/leu.2017.252.

  5. Immunoassay-Based Drug Tests Are Inadequately Sensitive for Medication Compliance Monitoring in Patients Treated for Chronic Pain.

    Science.gov (United States)

    Snyder, Marion L; Fantz, Corrine R; Melanson, Stacy

    2017-02-01

    Enzyme immunoassays (EIA) have notable limitations for monitoring therapeutic compliance in pain management. Chromatography coupled with mass spectrometry provides definitive results and superior sensitivity and specificity over traditional EIA testing. To analyze and compare the sensitivity of EIA results together with known prescriptions to liquid chromatography-tandem mass spectrometry (LC-MS/MS) for monitoring drug use (and abuse) in patients treated for chronic pain. A total of 530 urine samples from patients being treated for chronic pain were studied. Pain management clinic in the United States. The samples were tested for a profile of chronic pain medications and illicit drugs with commercially available EIA kits followed by analysis with Agilent LC-MS/MS system. The EIAs exhibited poor sensitivity and high rates of false negative results in the pain management setting. For example, 21% of EIA for opiates show false negative results. Mass spectrometry methods were more sensitive, detected a broader range of drugs and metabolites, and could detect non-prescribed drug use and simulations in compliance. Patients do not always accurately report drug use information, and some drugs do not have EIA methods available for comparative purposes. Mass spectrometry is a more robust and reliable method for detection of drugs used in the pain management setting. Due to the extent of undisclosed use and abuse of medications and illicit drugs, LC-MS/MS testing is necessary for adequate and accurate drug detection. In addition, LC-MS/MS methods are superior in terms of sensitivity and number of compounds that can be screened, making this a better method for use in pain management. Key words: Pain management, enzyme immunoassays, mass spectrometry, urine drug testing, prescription status, compliance.

  6. Analysis of Culture and Drug Sensitivity Tests of Mycoplasmas for 387 Patients with Nongonococcal Urethritis (Cervicitis) in Chongqing

    Institute of Scientific and Technical Information of China (English)

    翟志芳; 郝飞; 钟白玉; 黄秀英; 唐书谦; 刁庆春

    2004-01-01

    Objective: To investigate the prevalence of mycoplasma infections and the sensitivity to antibiotics among patients with nongonococcal urethritis or cervicitis (NGU) in Chongqing. Methods: 387 NGU cases with mycoplasma-positive results upon culture were analysed retrospectively. RESULTS: The majority of patients with mycoplasma infections were in the 20-40 year old age group. No significant difference was found between males and females. Ureaplasma urealyticum is the main pathogen of these NGU cases and no clear relationship between its concentration and pathogenic ability was noted. Drug sensitivity was tested against nine antibiotics; the sensitivity rates to josamycin, minocycline and doxycycline were 94.06%, 88.89% and 86.82% respectively, while the resistance rates to lincomycin, ofloxacin, azithromycin and roxthromycin were 74.94%, 42.12%, 41.60% and 40.31% in turn. Conclusions: Josamycin, minocycline and doxycycline could be used as the first choice to treat NGU with mycoplasma infections in Chongqing. It is important to select antibiotics for NGU treatment with mycoplasma infections based on the results of drug sensitivity tests.

  7. A new disposable electrode for electrochemical study of leukemia K562 cells and anticancer drug sensitivity test.

    Science.gov (United States)

    Yu, Chunmei; Zhu, Zhenkun; Wang, Li; Wang, Qiuhong; Bao, Ning; Gu, Haiying

    2014-03-15

    Developing cost-effective and simple analysis tools is of vital importance for practical applications in bioanalysis. In this work, a new disposable electrochemical cell sensor with low cost and simple fabrication was proposed to study the electrochemical behavior of leukemia K562 cells and the effect of anticancer drugs on cell viability. The analytical device was integrated by using ITO glass as the substrate of working electrodes and paper as the electrolytic cell. The cyclic voltammetry of the K562 cells at the disposable electrode exhibited an irreversible anodic peak and the peak current is proportional to the cell number. This anodic peak is attributed to the oxidation of guanine in cells involving two protons per transfer of two electrons. For the drug sensitivity tests, arsenic trioxide and cyclophosphamide were added to cell culture media. As a result, the electrochemical responses of the K562 cells decreased significantly. The cytotoxicity curves and results obtained corresponded well with the results of CCK-8 assays. In comparison to conventional methods, the proposed method is simple, rapid and inexpensive. More importantly, the developed sensor is supposed to be a single-use disposable device and electrodes were prepared "as new" for each experiment. We think that such disposable electrodes with these characteristics are suitable for experimental study with cancer cells or other types of pathogens for disease diagnosis, drug selection and on-site monitoring.

  8. Drugs of Abuse Testing

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Drug Abuse Testing Share this page: Was this page helpful? Also ... of Abuse Screen Related tests: Emergency and Overdose Drug Testing ; Ethanol ; Nicotine ; Phenobarbital ; Testosterone ; Growth Hormone ; Erythropoietin ; IGF- ...

  9. Haemophilus paragallinarum in chickens in Indonesia: III. Antimicrobial drug sensitivity test ofHaemophilus paragallinarum from chickens suffering of coryza

    OpenAIRE

    1998-01-01

    An agar disc diffusion method was used to examine the sensitivity of 27 Haemophilus paragallinarum (Hpg) isolates consisted of 23 local isolates, 4 standard isolates (serotype A) and Escherichia coli ATCC 24922 as a control to eight antimicrobial drugs (ampicillin, erythromycin, oxytetracycline, doxycycline, neomycin, streptomycin, colistine and sulphanlethoxazole-trimethoprim) . Twenty one out of 23 local isolates of Hpg were sensitive to doxycycline, 19 isolates to ampsllin, 18 isolates to ...

  10. Review of the efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing for patients with cancer.

    Science.gov (United States)

    Cortazar, P; Johnson, B E

    1999-05-01

    The purpose of this study is to review the potential efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing (DST) compared with empiric regimens for patients with cancer. MEDLINE and CANCERLIT were searched for articles published (in English) about prospective clinical trials in which patients were treated with chemotherapy that was selected with the use of in vitro DST. We identified 12 prospective studies that examined the benefit of chemotherapy selected by DST. Five hundred six patients (33%) were treated with chemotherapy that was selected with the use of in vitro DST. The mean response rate for patients treated with in vitro-selected therapy was 27% (range, 10% to 100%; n = 12 studies) compared with 18% (range, 0% to 100%; n = 7 studies) for patients treated with empiric therapy. Five studies (only one randomized) evaluated the impact of chemotherapy selected by in vitro DST on patient survival. Three studies showed that survival was 1 to 4 months longer for the 238 patients treated with empiric chemotherapy compared with that of the 65 patients treated with chemotherapy that was selected by in vitro testing. Two nonrandomized studies showed that survival was 4 or 19 months longer for 27 patients treated with chemotherapy selected by in vitro testing compared with that of 80 patients who were treated with empiric chemotherapy. Only one third of patients entered in prospective trials of in vitro DST were actually treated with an in vitro best regimen. The response rates seem to be better with in vitro selected chemotherapy regimens than with empiric regimens, but the impact on survival has not been adequately addressed.

  11. Assessment of the Worldwide Antimalarial Resistance Network Standardized Procedure for In Vitro Malaria Drug Sensitivity Testing Using SYBR Green Assay for Field Samples with Various Initial Parasitemia Levels.

    Science.gov (United States)

    Cheruiyot, Agnes C; Auschwitz, Jennifer M; Lee, Patricia J; Yeda, Redemptah A; Okello, Charles O; Leed, Susan E; Talwar, Mayank; Murthy, Tushar; Gaona, Heather W; Hickman, Mark R; Akala, Hoseah M; Kamau, Edwin; Johnson, Jacob D

    2016-04-01

    The malaria SYBR green assay, which is used to profilein vitrodrug susceptibility ofPlasmodium falciparum, is a reliable drug screening and surveillance tool. Malaria field surveillance efforts provide isolates with various low levels of parasitemia. To be advantageous, malaria drug sensitivity assays should perform reproducibly among various starting parasitemia levels rather than at one fixed initial value. We examined the SYBR green assay standardized procedure developed by the Worldwide Antimalarial Resistance Network (WWARN) for its sensitivity and ability to accurately determine the drug concentration that inhibits parasite growth by 50% (IC50) in samples with a range of initial parasitemia levels. The initial sensitivity determination of the WWARN procedure yielded a detection limit of 0.019% parasitemia.P. falciparumlaboratory strains and field isolates with various levels of initial parasitemia were then subjected to a range of doses of common antimalarials. The IC50s were comparable for laboratory strains with between 0.0375% and 0.6% parasitemia and for field isolates with between 0.075% and 0.6% parasitemia for all drugs tested. Furthermore, assay quality (Z') analysis indicated that the WWARN procedure displays high robustness, allowing for drug testing of malaria field samples within the derived range of initial parasitemia. The use of the WWARN procedure should allow for the inclusion of more malaria field samples in malaria drug sensitivity screens that would have otherwise been excluded due to low initial parasitemia levels.

  12. Haemophilus paragallinarum in chickens in Indonesia: III. Antimicrobial drug sensitivity test ofHaemophilus paragallinarum from chickens suffering of coryza

    Directory of Open Access Journals (Sweden)

    Sri Poernomo

    1998-12-01

    Full Text Available An agar disc diffusion method was used to examine the sensitivity of 27 Haemophilus paragallinarum (Hpg isolates consisted of 23 local isolates, 4 standard isolates (serotype A and Escherichia coli ATCC 24922 as a control to eight antimicrobial drugs (ampicillin, erythromycin, oxytetracycline, doxycycline, neomycin, streptomycin, colistine and sulphanlethoxazole-trimethoprim . Twenty one out of 23 local isolates of Hpg were sensitive to doxycycline, 19 isolates to ampsllin, 18 isolates to oxytetracycline, 17 isolates to sulphametoxazole-trimethoprim, 16 isolates to erythromycin, and 13 isolates to neomycin, while 13 isolates were resistance to colistine and 11 isolates were also resistance to streptomycin .

  13. Anticancer drug sensitivity by human tumor clonogenic assay.

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    Hiraki,Shunkichi

    1986-10-01

    Full Text Available The anticancer drug sensitivity of human cancers was tested by the human tumor clonogenic assay (HTCA. Of 152 human cancer specimens tested, 63 (41% formed more than 30 tumor cell colonies in control plates and could be used to evaluate the drug sensitivity of tumor cells. In 42 (93% of 45 clinical trials in 24 patients, a parallel correlation was observed between the in vitro anticancer drug sensitivity measured by the HTCA and the clinical response of tumors to anticancer drugs. These results suggest that the HTCA is a good technique for the in vitro test of the anticancer drug sensitivity of human cancers.

  14. Algorithms for Drug Sensitivity Prediction

    Directory of Open Access Journals (Sweden)

    Carlos De Niz

    2016-11-01

    Full Text Available Precision medicine entails the design of therapies that are matched for each individual patient. Thus, predictive modeling of drug responses for specific patients constitutes a significant challenge for personalized therapy. In this article, we consider a review of approaches that have been proposed to tackle the drug sensitivity prediction problem especially with respect to personalized cancer therapy. We first discuss modeling approaches that are based on genomic characterizations alone and further the discussion by including modeling techniques that integrate both genomic and functional information. A comparative analysis of the prediction performance of four representative algorithms, elastic net, random forest, kernelized Bayesian multi-task learning and deep learning, reflecting the broad classes of regularized linear, ensemble, kernelized and neural network-based models, respectively, has been included in the paper. The review also considers the challenges that need to be addressed for successful implementation of the algorithms in clinical practice.

  15. Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients.

    Science.gov (United States)

    Higashiyama, Masahiko; Oda, Kazuyuki; Okami, Jiro; Maeda, Jun; Kodama, Ken; Imamura, Fumio; Minamikawa, Kazuhiko; Takano, Toshikazu; Kobayashi, Hisayuki

    2010-06-01

    The collagen gel droplet embedded culture drug test (CD-DST), is an in vitro anticancer drug sensitivity test. The test has been used with various types of malignant tumors, but the significance of clinical application remains unknown. The aim of the present study is to evaluate the ability of this test to predict the response to chemotherapy in non-small cell lung cancer (NSCLC) patients. From January 2000 through March 2007, CD-DST data using the primary tumor specimens to anticancer drugs such as cisplatin (CDDP), carboplatin (CBDCA), paclitaxel (PAC), docetaxel (TXT), gemcitabine (GEM), and vinorelbine (VNR), was successfully obtained from 382 patients that underwent a radical resection for NSCLC. Eighty-one of those patients received 1st line chemotherapy using a "new generation" of anticancer drugs for postoperative recurrence. The chemotherapy regimen consisted of a CDDP (or CBDCA)-based combination (N=41), non-CDDP-based combination (N=1) and single agent (N=39). The predictability of the chemotherapeutic effect by the CD-DST data was analyzed retrospectively. Partial response (PR) was obtained in 24 patients (response rate=30%), stable disease (SD) in 33 (41%) and progressive disease (PD) in 24 (30%). Forty-two patients underwent chemotherapy with one or more CD-DST-sensitive drugs, 21 of whom showed PR (RR=50%), whereas only 3 (8%) patients showed PR with chemotherapy with regimen including no CD-DST-sensitive drugs. Good predictability was obtained, with a 50% positive predictive value (PPV) for PR and a 92% negative predictive value (NPV) by CD-DST. The predictive accuracy for the response based on the CD-DST data was 70%. Interestingly, a subset analysis according to recurrence site showed that the predictive accuracy was highest (86%) for CD-DST-based chemotherapy for recurrence in the lymph nodes. The application of the CD-DST for "new generation" anticancer drugs using surgically resected specimens of primary lesion in NSCLC patients may be

  16. In vitro drug sensitivity in canine lymphoma

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    Pawlak Aleksandra

    2016-03-01

    Full Text Available Introduction: Due to the high heterogeneity of canine lymphoma, the aim of the present study was to test in vitro the chemosensitivity of canine high-grade primary lymphoma cells to various cytostatic drugs commonly used to treat dogs: 4-HO-cyclophosphamide, doxorubicin, dexamethasone, prednisolone, vincristine, etoposide, chlorambucil, lomustine, and cytosine arabinoside. Material and Methods: To determine the cell viability and drug ability to induce apoptosis two different tests were used: an MTT assay and annexin V/propidium iodide staining. Results: Both in vitro tests were found to be useful tools. Significant differences in the sensitivity, depending on the drug type, between B-, T- and mixed/null-type lymphoma cells were found for the majority of the tested drugs. B-type cells were the most sensitive in vitro, whereas T-type cells seemed to be the most resistant. Doxorubicin, chlorambucil, etoposide, and vincristine most strongly reduced the cell viability and induced apoptosis. Conclusion: In vitro assays, such as the MTT test and especially the annexin V/PI assay, may be useful tools for predicting a response to the treatment of high-grade lymphoma in dogs or improving the treatment outcomes in individual animals.

  17. Simple flow cytometric detection of haemozoin containing leukocytes and erythrocytes for research on diagnosis, immunology and drug sensitivity testing

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    Grobusch Martin P

    2011-03-01

    . Conclusions A simple modification of a flow cytometer allows for rapid and reliable detection and quantification of Hz-containing leukocytes and the analysis of differential surface marker expression in the same sample of Hz-containing versus non-Hz-containing leukocytes. Importantly, it distinguishes different maturation stages of parasitized RBC and may be the basis of a rapid no-added-reagent drug sensitivity assay.

  18. Monitoring the drug-sensitivity of Plasmodium falciparum in coastal towns in Madagascar by use of in vitro chemosensitivity and mutation detection tests

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    Rason M.A.

    2002-09-01

    Full Text Available The dissemination of mutant and resistant strains of Plasmodium falciparum makes a considerable contribution to the spread of drug-resistant malaria. Populations around harbours and airports could be particularly exposed to Plasmodium isolates introduced with imported cases of malaria. The use of chloroquine as well as the use of and sulfadoxine/pyrimethamine is currently an effective method for treating uncomplicated cases of malaria in Madagascar. As part of a monitoring programme, in vitro methods were used to assess the sensitivity of P. falciparum isolates in two coastal towns in Madagascar: Mahajanga on the west coast and Toamasina on the east coast. All of the isolates from both sites were sensitive to amodiaquine, quinine, pyrimethamine and cycloguanil. All of the isolates from Mahajanga were sensitive to chloroquine (n = 25; mean IC50 = 22.6 nM, 95 % confidence interval: 16.8-28.7 nM, whereas three of the isolates from Toamasina were resistant to chloroquine (n = 18; mean IC50 = 66.3 nM; 95 % confidence interval : 42.6-90 nM, The frequency of the Pfcrt Thr-76 and the dhfr Asn- 108 mutations was estimated by PCR/RFLP. The 43 P. falciparum isolates examined, including the three in vitro chloroquine-resistant isolates from Toamasina were all wild-type (Lys-76. Phenotyping and genotyping studies suggested that the prevalence of chloroquine- and pyrimethamine-resistant isolates and of mutant strains of P. falciparum is very low. These results showed that in vitro test and genotyping of resistance markers approaches could be successfully used to monitor the emergence of drug-resistant malaria and to try to alleviate the lack of medical teams able to carry out in vivo test. The possible hazard/risk associated with imported cases of malaria is discussed.

  19. Price Sensitivity of Demand for Prescription Drugs

    DEFF Research Database (Denmark)

    Skipper, Lars; Simonsen, Marianne; Skipper, Niels

    This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity....

  20. Survival of patients with limited-stage small cell lung cancer treated with individualized chemotherapy selected by in vitro drug sensitivity testing.

    Science.gov (United States)

    Cortazar, P; Gazdar, A F; Woods, E; Russell, E; Steinberg, S M; Williams, J; Ihde, D C; Johnson, B E

    1997-05-01

    Our purpose was to study the feasibility of determining individualized chemotherapy regimens by in vitro drug sensitivity testing (DST) for patients with limited-stage small cell lung cancer (SCLC) and to evaluate patient response and survival. Fifty-four previously untreated patients with limited-stage small cell cancer were studied. Fresh tumor specimens for DST were collected, when possible, from patients' biopsies before the start of treatment. The differential staining cytotoxicity assay was used to determine the in vitro sensitivity of the tumor cells to different drugs. From these results, an in vitro best regimen (IVBR), a three-drug combination of previously proven efficacy of seven active drugs in SCLC, was selected. Patients were initially treated with four cycles of etoposide/cisplatin and concurrent radiotherapy. This was followed by four cycles of either individualized chemotherapy regimens based on the results of DST or, when DST results were not available, four cycles of vincristine, doxorubicin, and cyclophosphamide. Eighteen patients (33%) underwent biopsy procedures that provided tissue specimens for DST. The biopsy specimens contained tumor cells in 16 of 18 patients. The median duration from diagnosis to start of treatment was 22 days (range, 4-58 days) for the 18 patients who underwent elective thoracic biopsies compared to 21 days (range, 2-74 days) for members of the group that did not (P2 = 0.58). Time from thoracic biopsy to initiation of chemotherapy was a median of 4 days (range, 2-22 days). DST was done in 10 patients, and IVBR was administered to 8 patients. The median actuarial survival of 8 patients treated with their IVBR was 38.5 months compared to 19 months for the 46 patients treated with empiric chemotherapy. Selection of individualized chemotherapy regimens is labor intensive but feasible in limited-stage SCLC. Treatment with an individualized IVBR in our patients was associated with prolonged patient survival; however, because

  1. Local Sensitivity and Diagnostic Tests

    NARCIS (Netherlands)

    Magnus, J.R.; Vasnev, A.L.

    2004-01-01

    In this paper we confront sensitivity analysis with diagnostic testing.Every model is misspecified, but a model is useful if the parameters of interest (the focus) are not sensitive to small perturbations in the underlying assumptions. The study of the e ect of these violations on the focus is calle

  2. An analysis of sensitivity tests

    Energy Technology Data Exchange (ETDEWEB)

    Neyer, B.T.

    1992-03-06

    A new method of analyzing sensitivity tests is proposed. It uses the Likelihood Ratio Test to compute regions of arbitrary confidence. It can calculate confidence regions for the parameters of the distribution (e.g., the mean, {mu}, and the standard deviation, {sigma}) as well as various percentiles. Unlike presently used methods, such as those based on asymptotic analysis, it can analyze the results of all sensitivity tests, and it does not significantly underestimate the size of the confidence regions. The main disadvantage of this method is that it requires much more computation to calculate the confidence regions. However, these calculations can be easily and quickly performed on most computers.

  3. 鸭疫里氏杆菌的分离鉴定及药敏试验%Isolation, Identification and Drug-sensitivity Tests of Riemerella anatipestifer Isolates

    Institute of Scientific and Technical Information of China (English)

    潘淑惠; 王璇; 郭光容; 徐景峨; 吴位珩; 杨莉; 余波

    2011-01-01

    为鸭疫里氏杆菌病的防治提供参考,2009年5月,对贵州某肉鸭养殖场送检病鸭进行了剖检病变观察、细菌分离鉴定,并进行了药敏试验.结果表明,分离细菌通过细菌形态、染色特性、生化试验、培养特征鉴定为鸭疫里氏杆菌,7株菌对头孢拉定、头孢曲松钠、头孢噻肟和氟苯尼考高度敏感,对庆大霉素、新霉素、青霉素、多粘菌素B、氟哌酸、复方新诺明、链霉素和卡那霉素耐药.%To make references for prevention and treatment of Riemerella anatipestifer, in May 2009, pathological changes of sick duck was observed, bacteria were isolated and identified and drug-sensitivity tests were carried out in Guizhou meat duck farm. The results showed that the isolated bacteria were identified as Riemerella anatipestifer by bacterium form, biochemistry and cultured characteristics. The seven strains were highly susceptible to cefradine, ceftriaxone sodium, cefotaxime, florfenicol, not susceptible to gentamicin, neomycin, penicillin, polymyxin B, norfloxacin, sinomin compositea, streptomycin and kanamycin.

  4. Price Sensitivity of Demand for Prescription Drugs

    DEFF Research Database (Denmark)

    Simonsen, Marianne; Skipper, Lars; Skipper, Niels

    2016-01-01

    We investigate price sensitivity of demand for prescription drugs, using drug purchase records for the entire Danish population. We identify price responsiveness by exploiting variation in prices caused by kinked reimbursement schemes and implement a regression kink design. The results suggest so...... price responsiveness with corresponding price elasticities ranging from −0.2 to −0.7. Individuals with chronic disease and especially individuals above the age of 65 respond less to the price of drugs.......We investigate price sensitivity of demand for prescription drugs, using drug purchase records for the entire Danish population. We identify price responsiveness by exploiting variation in prices caused by kinked reimbursement schemes and implement a regression kink design. The results suggest some...

  5. Drug testing in American schools

    Directory of Open Access Journals (Sweden)

    C.J. Russo

    2003-08-01

    Full Text Available As the use of illegal drugs has reached epidemic proportions in schools, educational leaders in the United States have turned to drug testing in attempting to maintain learner discipline. To this end, the United States Supreme Court has addressed the issue twice in the past eight years. In 1995, the Court permitted drug testing in Acton v. Vernonia School District 47J. More recently, in Board of Education of Independent School District No. 92 of Pottawatomie v. Earls (2002, the Court upheld suspicionless drug testing of learners who wished to participate in extracurricular activities. Even though drug testing has yet to emerge as an issue in South Africa, Earls is significant for educational leaders and policy makers in South Africa since it involves concerns under the National Policy on Privacy. More specifically, under Items 20 and 21 of the South African National Policy on the Management of Drug Abuse (SA, 1996b searches and drug testing should only be used where there is reasonable suspicion, the same standard applied by American courts. However, unlike the United States, the South African policy prohibits random searches and/or drug testing. Thus, due to constitutional and educational issues that drug testing raises, a timely discussion of this matter should be of interest to educational leaders and policy makers in South Africa.

  6. Adulterants in Urine Drug Testing.

    Science.gov (United States)

    Fu, S

    Urine drug testing plays an important role in monitoring licit and illicit drug use for both medico-legal and clinical purposes. One of the major challenges of urine drug testing is adulteration, a practice involving manipulation of a urine specimen with chemical adulterants to produce a false negative test result. This problem is compounded by the number of easily obtained chemicals that can effectively adulterate a urine specimen. Common adulterants include some household chemicals such as hypochlorite bleach, laundry detergent, table salt, and toilet bowl cleaner and many commercial products such as UrinAid (glutaraldehyde), Stealth® (containing peroxidase and peroxide), Urine Luck (pyridinium chlorochromate, PCC), and Klear® (potassium nitrite) available through the Internet. These adulterants can invalidate a screening test result, a confirmatory test result, or both. To counteract urine adulteration, drug testing laboratories have developed a number of analytical methods to detect adulterants in a urine specimen. While these methods are useful in detecting urine adulteration when such activities are suspected, they do not reveal what types of drugs are being concealed. This is particularly the case when oxidizing urine adulterants are involved as these oxidants are capable of destroying drugs and their metabolites in urine, rendering the drug analytes undetectable by any testing technology. One promising approach to address this current limitation has been the use of unique oxidation products formed from reaction of drug analytes with oxidizing adulterants as markers for monitoring drug misuse and urine adulteration. This novel approach will ultimately improve the effectiveness of the current urine drug testing programs. © 2016 Elsevier Inc. All rights reserved.

  7. Pathogens distribution and drug sensitivity of chronic dacryocystitis

    Directory of Open Access Journals (Sweden)

    Yang-Yang Xie

    2014-10-01

    Full Text Available AIM: To analyze the pathogens and drug sensitivity of chronic dacryocystitis in order to provide evidence for clinical drug use.METHODS: Lacrimal secretion of 171 cases with chronic dacryocystitis was sampled for pathogenic bacteria culture identification and drug sensitivity test. Based on the results, the isolation rate of pathogens strains, the pathogens kind of chronic dacryoeystitis, main pathogens of chronic dacryocystitis, and sensitive drug for pathogens were analyzed.RESULTS: The isolation rate of pathogens strains was 76.61%(131 cases. The pathogens constituting the chronic dacryocystitis were predominantly gram-positive coccus,the percentage was 72.52%(95 cases, among which staphylococcus hominis occupied 27.48%(36 cases, staphylococcus epidermidis 16.79%(22 cases, streptococcus viridans 12.98%(17 cases. The majority of these bacteria were sensitive to cefoperazone-sulbactam, tobramycin, gentamicin and levofloxacin. For gram-positive coccus, cefoperazone-sulbactam, gentamicin and tobramycin were the most sensitive drug. For gram-negative bacilli, cefoperazone-sulbactam, tobramycin and levofloxacin were most sensitive drug.CONCLUSION: Staphylococcus hominis is the main pathogen of chronic dacryocystitis, tobramycin can be used as the first choice for local treatment of chronic dacryocystitis.

  8. Health care organization drug testing.

    Science.gov (United States)

    Brooks, J P; Dempsey, J

    1992-09-01

    Health care managers are being required to respond to the growing concerns of the public about alcohol and drug use in the health care workplace. To this end, the following recommendations are offered. A drug testing policy should be developed with input from and support of employees and unions. "For cause" testing should be used because it results in more definitive results and better employee acceptance. Unless there are compelling reasons for random testing, "for cause" testing is the preferable method. All levels of employees and the medical staff should be subject to the drug-testing policy. Rehabilitation rather than punishment should be emphasized in dealing with employees with alcohol and drug problems.

  9. Implications of Drug Testing Cheerleaders

    Science.gov (United States)

    Trachsler, Tracy A.; Birren, Genevieve

    2016-01-01

    With the untimely death of a University of Louisville cheerleader due to an accidental drug overdose in the summer of 2014, the athletic department representatives took steps to prevent future incidents by adding cheerleaders to the randomized drug testing protocols conducted at the university for the student-athletes involved in National…

  10. Common Interferences in Drug Testing.

    Science.gov (United States)

    Smith, Michael P; Bluth, Martin H

    2016-12-01

    Interferences relating to laboratory toxicology testing refer to results which differ from their true value and are often encountered in the setting of a drug screen compared with confirmatory testing. Such interferences fall into two general categories; those that cause false positive results (when a drug screen is positive but confirmatory testing is negative) and those that cause false negative results (when a drug screen is negative when in reality the sample donor has ingested the tested substance). Such interferences can result from differences in laboratory testing methodology, reagent and analyte cross reactivity, limits of analyte detection, instrument resolution, reporting cutoff, sample processing, tissue type and sample adulteration among others. Awareness of the possible causes of such interferences are integral to proper laboratory result interpretation and patient management. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Combined Species Identification and Drug Sensitivity Testing in Mycobacteria.

    Science.gov (United States)

    Ceyssens, Pieter-Jan; Soetaert, Karine; Timke, Markus; Van den Bossche, An; Sparbier, Katrin; De Cremer, Koen; Kostrzewa, Markus; Hendrickx, Marijke; Mathys, Vanessa

    2017-02-01

    Species identification and drug susceptibility testing (DST) of mycobacteria are important yet complex processes traditionally reserved for reference laboratories. Recent technical improvements in matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has started to facilitate routine mycobacterial identifications in clinical laboratories. In this paper, we investigate the possibility of performing phenotypic MALDI-based DST in mycobacteriology using the recently described MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA). We randomly selected 72 clinical Mycobacterium tuberculosis and nontuberculous mycobacterial (NTM) strains, subjected them to MBT-ASTRA methodology, and compared its results to current gold-standard methods. Drug susceptibility was tested for rifampin, isoniazid, linezolid, and ethambutol (M. tuberculosis, n = 39), and clarithromycin and rifabutin (NTM, n = 33). Combined species identification was performed using the Biotyper Mycobacteria Library 4.0. Mycobacterium-specific MBT-ASTRA parameters were derived (calculation window, m/z 5,000 to 13,000, area under the curve [AUC] of >0.015, relative growth [RG] of drug resistance profiles which corresponded to standard testing results. Turnaround times were not significantly different in M. tuberculosis testing, but the MBT-ASTRA method delivered on average a week faster than routine DST in NTM. Databases searches returned 90.4% correct species-level identifications, which increased to 98.6% when score thresholds were lowered to 1.65. In conclusion, the MBT-ASTRA technology holds promise to facilitate and fasten mycobacterial DST and to combine it directly with high-confidence species-level identifications. Given the ease of interpretation, its application in NTM typing might be the first in finding its way to current diagnostic workflows. However, further validations and automation are required before routine implementation can be envisioned

  12. Are standard tests sensitive enough to evaluate effects of human pharmaceuticals in aquatic biota? Facing changes in research approaches when performing risk assessment of drugs.

    Science.gov (United States)

    Aguirre-Martínez, G V; Owuor, M A; Garrido-Pérez, C; Salamanca, M J; Del Valls, T A; Martín-Díaz, M L

    2015-02-01

    Nowadays, the presence of pharmaceutical products in aquatic environments is not only common, but is also of significant concern regarding the adverse effect they may produce to aquatic biota. In order to determine the adverse effects of caffeine (CAF), ibuprofen (IBU), carbamazepine (CBZ) and novobiocin (NOV), at environmental occurring concentrations, standardized endpoints applied in current guidelines were evaluated in four organisms including bioluminescence response in Vibrio fischeri, growth inhibition in Isochrysis galbana (marine water) and Pseudokirchneriella subcapitata (fresh water) and fertilization and embryo-larval development in Paracentrotus lividus. To reach this aim bioassays were implemented by exposing organisms to water spiked with drugs dissolved in DMSO (0.001% v/v). Risk characterization was performed, calculating the environmental impact of drugs by calculating environmental concentration and predicted no effect concentration ratio (MEC/PNEC). Results indicate that acute toxicity was found above environmental concentrations in the order of mg L(-1) for bacteria bioluminescence, microalgae growth inhibition and sea urchin fertilization. However, teratogenicity was observed on sea urchin after exposure to environmental concentrations of drugs at 0.00001 mg L(-1); at this concentration CBZ and IBU were found to reduce significantly the embryo-larval development compared to controls (p<0.01). The risk calculated for selected drugs suggested they are harmless for aquatic environment except when applying the embryo-larval development endpoint. Endpoints applied in this study showed the necessity of using more sensitive responses, when assessing risk of pharmaceuticals in aquatic environments, since endpoints applied in current guidelines may not be suitable.

  13. Current trend of drug sensitivity in bovine mastitis

    Directory of Open Access Journals (Sweden)

    Rajeev Ranjan

    2010-02-01

    Full Text Available The study was conducted on 190 milk samples of bovine mastitis and 138 samples were confirmed positives for microorganisms. All the 138 samples were subjected to drug sensitivity test. The most effective antibiotic was enrofloxacin (91.67% followed by ciprofloxacin (90.15%, amikacin (87.12%, ceftriaxone (84.10%, chloramphenicol (80.31%, cefotaxime (79.55% and gentamicin (77.27%. Microorganisms were mostly resistant to drugs like streptomycin, penicillinG, ampicillin, cloxacillin, amoxycillin and neomycin in increasing order of resistance. Hence, it is suggested that the line of treatment should be based on antibiogram study of various isolates from bovine mastitis. Further, the selection of drugs after culture and sensitivity test should be based on their ability to cross blood tissue barrier or mammary parenchyma, lipophilicity and ability to work in alkaline pH. [Vet. World 2010; 3(1.000: 17-20

  14. Direct Comparison of the Histidine-rich Protein-2 Enzyme-linked Immunosorbent Assay (HRP-2 ELISA) and Malaria SYBR Green I Fluorescence (MSF) Drug Sensitivity Tests in Plasmodium falciparum Reference Clones and Fresh ex vivo Field Isolates from Cambodia

    Science.gov (United States)

    2013-07-12

    RESEARCH Open Access Direct comparison of the histidine -rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR green I...Walsh1, David L Saunders1 and Charlotte A Lanteri1* Abstract Background: Performance of the histidine -rich protein-2 enzyme-linked immunosorbent... histidine -rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR green I fluorescence (MSF) drug sensitivity tests in

  15. A Recombinant Human Pluripotent Stem Cell Line Stably Expressing Halide-Sensitive YFP-I152L for GABAAR and GlyR-Targeted High-Throughput Drug Screening and Toxicity Testing

    Science.gov (United States)

    Kuenzel, Katharina; Friedrich, Oliver; Gilbert, Daniel F.

    2016-01-01

    GABAARs and GlyRs are considered attractive drug targets for therapeutic intervention and are also increasingly recognized in the context of in vitro neurotoxicity (NT) and developmental neurotoxicity (DNT) testing. However, systematic human-specific GABAAR and GlyR-targeted drug screening and toxicity testing is hampered due to lack of appropriate in vitro models that express native GABAARs and GlyRs. We have established a human pluripotent stem cell line (NT2) stably expressing YFP-I152L, a halide-sensitive variant of yellow fluorescent protein (YFP), allowing for fluorescence-based functional analysis of chloride channels. Upon stimulation with retinoic acid, NT2 cells undergo neuronal differentiation and allow pharmacological and toxicological evaluation of native GABAARs and GlyRs at different stages of brain maturation. We applied the cell line in concentration-response experiments with the neurotransmitters GABA and glycine as well as with the drugs strychnine, picrotoxin, fipronil, lindane, bicuculline, and zinc and demonstrate that the established in vitro model is applicable to GABAAR and GlyR-targeted pharmacological and toxicological profiling. We quantified the proportion of GABAAR and GlyR-sensitive cells, respectively, and identified percentages of approximately 20% each within the overall populations, rendering the cells a suitable model for systematic in vitro GABAAR and GlyR-targeted screening in the context of drug development and NT/DNT testing. PMID:27445687

  16. The Analysis Results of Detection and Drug Sensitivity Test of Pathogens in 183 Cases of Children with Diarrhea%183例腹泻儿童病原学检测及药敏试验结果分析

    Institute of Scientific and Technical Information of China (English)

    王文雅; 张秀敏; 杜会双

    2016-01-01

    目的:腹泻儿童病原学检测及药敏试验结果分析。方法对我院183例腹泻儿童进行病原学检测和药物敏感试验,分析结果。结果腹泻患儿大便病原菌主要有G+菌、大肠埃希菌、志贺菌、沙门菌等。药敏试验结果显示金黄色葡萄球菌、大肠埃希菌、志贺菌和沙门菌对左氧氟沙星、亚胺培南、阿米卡星敏感度较高,而对传统的一线抗生素阿莫西林、头孢噻肟和红霉素类抗菌药敏感度较低。结论腹泻儿童在治疗中最好根据病原学诊断和病原菌,选择合理的抗生素。%Objective To analyze children with diarrhea pathogen detection and drug sensitivity test.Methods 183 cases of children with diarrhea pathogen detection and drug sensitivity test results.Results diarrhea stool pathogens are mainly G+ bacteria, Escherichia coli, Shigella, Salmonella etc. Drug sensitivity test showed that Staphylococcus aureus, Escherichia coli, Shigella and Salmonella of levolfoxacin, imipenem, amikacin sensitivity higher, while to the traditional ifrst-line antibiotics amoxicillin, cefotaxime and erythromycin antibiotics sensitivity is low.Conclusion In the treatment of children with diarrhea in the best according to the etiological diagnosis and pathogenic bacteria, reasonable selection of antibiotics.

  17. The Time Delay Between Drug Intake and Bronchospasm for Nonsteroidal Antiinflammatory Drugs Sensitive Patients

    Science.gov (United States)

    2010-01-01

    A study was performed to assess the time between drug intake and drug induced hypersensitivity reaction for patients sensitive to nonsteroidal antiinflammatory drugs (NSAID) in clinical patient history and after oral provocation tests. Drug hypersensitivity ENDA questionnaires were filled for the patients with suspected sensitivity to NSAID. Oral provocation tests were performed with suspected NSAID according to the ENDA/EAACI recommendations. There were 76 patients with history of hypersensitivity reactions after use of NSAID enrolled in the study. Recorded were 154 hypersensitivity reactions to NSAID in the clinical history. In the clinical history median time of immediate reactions (76 cases, 81%) between drug intake and bronchospasm was 20 minutes [15-30 minutes]. Median time of nonimmediate reactions (18 cases, 19%) was 120 minutes [120-390 minutes]. There were 50 oral provocation tests performed, 14 of them (28%) were positive. Median time between drug intake and immediate reactions (8; 57% of cases) was 22.5 minutes [20-30 minutes] and median time of nonimmediate reactions (6; 43% of cases) was 167.5 minutes [125-206.25 minutes]. Time delay between drug intake and bronchospasm in the clinical history and after oral provocation test was not statistically different. PMID:23282984

  18. 49 CFR 655.21 - Drug testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Drug testing. 655.21 Section 655.21 Transportation... TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Drug Use § 655.21 Drug testing. (a) An employer shall establish a program that provides testing for prohibited...

  19. 75 FR 3153 - Drug and Alcohol Testing Program; Correction

    Science.gov (United States)

    2010-01-20

    ... flights, Commercial air tour operators, Drug testing, Operators, Safety, Safety-sensitive, Transportation... applicable regulations; and added wording when describing an operator. This rule corrects those inadvertent... requirements on operators affected by these regulations. DATES: Effective January 20, 2010. FOR...

  20. Isolation Identification and Drug Sensitive Test of Avian Escherichia coli in the Area of Jinzhou%锦州地区鸡大肠杆菌的分离鉴定及耐药性分析

    Institute of Scientific and Technical Information of China (English)

    李冰; 唐峰; 马鸣潇

    2011-01-01

    Samples were collected from the chiken that suspected as colibacillosis in Jinzhou district, 15 strains of Avian E.coli were isolated. They were belonged to 14 serotypes, Serotype O15, O35 constituted a majority of the isolates. Drug sensitive test were carried out on the 10 strains, the result showed that drug resistance and multi-drug resistant was serious. The sistant rate were 46.67%-100%, about 86.67% strains resist to more than 5 drugs in the test.%由锦州地区不同类型鸡场采集疑似大肠杆菌病病料,分离出大肠杆菌15株.血清型鉴定试验确定14株的血清型,优势血清型为O15,O35.并选择10种抗生素进行药敏试验,结果表明实验菌株耐药程度和多重耐药较为严重,耐药率在46.67%~100%,对5种以上抗生素耐药的菌株共有13株,占86.67%.

  1. [Procedure for determination of individual sensitivity to antitumor drugs].

    Science.gov (United States)

    Abduvaliev, A A; Gil'dieva, M S; Tatarskiĭ, V P

    2006-05-01

    The present paper proposes to employ the cultured tumor cells of the breast and chick fibroblasts after long-term cultivation (for above 24 days) to determine their individual drug sensitivity and, as a criterion of cell damage, to use the percent of destruction of the cell layer formed in the wells 24 hours after drug insertion. It also presents the comparative results of tests of 2 cellular models that have been used to determine the in vitro sensitivity of the cells of breast cancer and chick fibroblasts to melfalan and its complex compound with copper acetylacetonate - MOK*M. At the same time, the cytotoxic activity of MOK*M and melfalan against tumor cells has been not shown to differ greatly (16.02+/-1.85 and 15.71+/-0.65% cell layer destruction, respectively), but the same activity of MOK*M against the model of intact cells (chick fibroblasts) was much less (15.23+/-1.97%) than that of melfalan (95.39+/-1.11%). The test system proposed by the authors is of certain informative value and it may be used for the determination of the individual sensitivity of tumor cells to antitumor drugs.

  2. 78 FR 22209 - Additional Synthetic Drug Testing

    Science.gov (United States)

    2013-04-15

    ... COMMISSION 10 CFR Part 26 Additional Synthetic Drug Testing AGENCY: Nuclear Regulatory Commission. ACTION... NRC amend its Fitness for Duty program regulations to amend drug testing requirements to test for... raised in the PRM are appropriate for consideration in an ongoing rulemaking on Drug and Alcohol Testing...

  3. 神经内科重症监护病房病原菌分布及药敏分析%Characteristic Description and Drug Sensitivity Testing of Pathogenic Bacteria in Neurological Intensive Care Unit

    Institute of Scientific and Technical Information of China (English)

    李海英; 李淑娟; 胡文立; 秦伟

    2011-01-01

    Objective The characteristic of infection strains and the changes in antibiotic-resistance in neurological intensive care unit(NICU) were investigated to direct the antibiotics clinical application, and to reduce the hospital infection incidence rates. Methods From Sep. 2008 to May 2010,451 species from 216 patients in N1CU, including sputum, urine, stools, and blood, were cultured for bacteria identification and drug sensitivity testing. Results Among the isolated 399 strains of pathogenic bacteria,Gram-negative bacilli,Gram-positive cocci and fungi, were 140,73 and 186, respectively. The pathogens were mainly from respiratory tract. As the major pathogens, Candida albicans and Staphylococcus aureu accounted for 49.9% of all pathogens. The results of drug sensitivity testing showed that fungi had great clinical drug resistance; MRSA showed high sensitivity to Glyco-peptides-type drugs;and Gram-negative bacilli showed sensitivity to Carbapenem-type drugs. Cephalosporin-type and Penicillin-type drugs showed different sensitivities to the Gram-negative bacilli. Conclusion The main pathogenic bacteria of NICU were fungi and Gram-negative bacilli, which might be the contribution of extensive use of broad-spectrum antibiotics. The doctors should pay attention to reduce the use of broad-spectrum antibiotics,appropriately increase the use of Glycopeptides-type and Carbapenem-type drugs. Cefoperazone/sulbactam or ceftazidime was suggested as the conventional antiseptic drug.%目的 调查神经内科重症监护病房(NICU)感染患者的病原菌分布及耐药情况,以指导临床抗菌药物的应用,降低医院感染率.方法 对2008年9月-2010年5月期间入住NICU的216例患者送检的痰、尿、便、血等451份标本进行病原菌鉴定和体外药敏试验.结果检出的399株病原菌中,G-杆菌140株,G+球菌73株,真菌186株.病原菌主要采自于呼吸道.致病菌简单且集中,白色念珠菌和MRSA占所有致病菌的49.9%.药敏结果

  4. The pus bacterial cultivation and drug sensitive test analysis of chronic suppurative otitis media in 81 cases%81例慢性化脓性中耳炎脓液细菌培养及药敏分析

    Institute of Scientific and Technical Information of China (English)

    胡春梅; 陈德珍; 何刚

    2015-01-01

    目的:分析入院拟手术的慢性化脓性中耳炎患者耳部感染的菌群分布及药敏结果,寻找敏感的抗生素,指导临床合理用药。方法81例诊断慢性化脓性中耳炎入院拟行手术的患者耳道分泌物进行细菌培养及药敏试验,对培养阳性菌株的种类以及药物敏感试验结果进行统计分析。结果81份标本中分离出致病菌43株,阳性率53%,革兰氏阳性球菌24株(55.8%),以金黄色葡萄球菌及星座链球菌为主;革兰氏阴性杆菌17株(39.5%),以铜绿假单胞菌,肺炎克雷伯菌,大肠埃希菌为主,真菌2株(4.6%)。革兰氏阳性菌普遍对碳青霉烯,万古霉素类抗生素敏感,革兰氏阴性菌普遍对莫西沙星,碳氢霉烯类,万古霉素等抗生素敏感,结论革兰氏阳性菌是本地区慢性化脓性中耳炎的主要致病菌,临床需根据药敏结果选择安全有效的药物治疗。%Objective Analysis of the distribution of pathogenic bacteria and its drug sensitivity of chronic suppurative otitis media in patients to be operated ,searching for sensitive antibiotics and guiding clinical rational drug use .Methods The bacterial culture and drug sensitivity test were carried out on the patient's ear canal secretion with chronic suppurative otitis media admitted to be treated with surgery ,and the type of positive strains and drug sensitivity test results were statistically analyzed .the results were statisticallyanalyzed.Results 43strainspathogenicbacteriaweredetectedin81samples,andthepositive rate was 53% .Gram positive bacteria were 24 (55 .8% ) ,mainly staphylococcus aureus and streptococcus constellation ;.gram negative bacilli were 17 (39 .5% ) ,mainly pseudomonas aeruginosa ,klebsiella pneumoniae ,escherichia coli;Fungi were 2 strains (4 .6% ) .Gram positive bacteria were sensitivated to carbapenems and vancomycin ,while gram negative bacteria generally to moxifloxacin ,carbapenems and

  5. 76 FR 59574 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs: Federal Drug Testing...

    Science.gov (United States)

    2011-09-27

    ... Alcohol Testing Programs: Federal Drug Testing Custody and Control Form; Technical Amendment AGENCY... of a new Federal Drug Testing Custody and Control Form (CCF) in its drug testing program. Use of the... amendment to its drug testing procedures by amending a provision of the rule which was inadvertently omitted...

  6. 暹罗斗鱼致病性嗜水气单胞菌的分离·鉴定及药敏试验%Isolation, Identification and Drug Sensitivity Test of Pathogenic Aeromonas hydrophila from Betta splendens Regan

    Institute of Scientific and Technical Information of China (English)

    杨宁; 黄海; 张希; 魏赟; 巫火连

    2012-01-01

    [Objective] The research aimed to discuss the disease cause of Betta splcnders Regan and the prevention and control methods of its diseases and pests. [Method] The pathogenic bacteria of B, splenders were isolated and identified by determining die physiological and biochemical indices and 16 S rDNA sequencing. And the drug sensitivity test was made. [Result] Strain DY001 was the pathogenic bacteria that caused Aeromonas hydrophila disease of B. splenders. Strain DY001 was identified as Aeromonas hydrophila. The median lethal dose (LD50) of this pathogeny to B. splenders was 0. 04 × 106 CFU/g. The results of drug sensitivity test showed that this pathogenic bacteria was sensitive to azithromycin, ofloxacin, norfloxacin, compound sinomin, ceftriaxone, trimethoprim, chloramphenicol and other antibiotics. [Conclusion] Aeromonas hydropkila was the pathogenic bacteria that caused the disease incidence of B. splenders. The results of drug sensitivity test could provide references for the disease prevention and control of B. splenders.%[目的]探讨暹罗斗鱼的发病原因和病害防治方法.[方法]对暹罗斗鱼的病原菌进行分离,并通过生理生化指标测定和16S rDNA测序对其鉴定,同时进行药敏试验.[结果]菌株DY001为暹罗斗鱼嗜水气单胞菌病的病原菌.经鉴定,确定菌株DY001为嗜水气单胞菌(Aeromonas hydrophila).该病原菌对暹罗斗鱼的半致死量(LD50)为0.04×106 CFU/g.药敏试验结果表明,病原菌对阿奇霉素、奥复星、氟哌酸、复方新诺明、菌必治、甲氧苄啶和氯霉素等抗生素敏感.[结论]嗜水气单胞菌是引起此次暹罗斗鱼发病的病原菌,而药敏试验结果将为其防治提供参考.

  7. 儿童假丝酵母感染状况分析及药物敏感性研究%Analysis on the infection status of Candida in children and the drug sensitive test

    Institute of Scientific and Technical Information of China (English)

    王长嘉; 孙晓红; 贺丹; 李广泉; 高磊; 高嵩; 王丽

    2012-01-01

    目的:探讨儿童假丝酵母的感染情况,分析其对常用抗真菌药物的敏感性,为真菌感染的治疗和预防提供依据.方法:收集临床假丝酵母感染患儿标本77例,进行菌株的分离、鉴定.并从患儿年龄、基础疾病及标本来源、检出病原菌种类、菌株药物敏感性等方面进行分析.结果:真菌感染患儿的平均年龄为6岁.标本主要来源于咽拭子,白假丝酵母的分离率最高(63.6%),其次为光滑假丝酵母、热带假丝酵母、克柔假丝酵母和其他假丝酵母.药物敏感性实验结果表明,假丝酵母对两性霉素B (AmB)、5-氟胞嘧啶(5- FC)的敏感性较高.其中,白假丝酵母对AmB、5- FC、氟康唑(FCZ)及伊曲康唑(ICZ)的敏感率依次为100.0%、91.9%、83.7%、69.4%;对ICZ、FCZ、5- FC的耐药率依次为4.1%、2.0%、2.0%.结论:儿童真菌感染以白假丝酵母最多见,分离菌株对FCZ和ICZ的耐药性较高,临床医生应高度重视,并根据药物敏感性实验结果进行治疗和预防.%Objective: To explore the infection status of Candida in children, analyze its sensitivity to antibiotics commonly used in clinic, provide a basis for the treatment and prevention of fungal infection. Methods; A total of 77 specimens of clinical infection of Candida in children were collected, then isolation and identification of bacterial strains were conducted, then the results were analyzed from the aspects of age, basic diseases, source of specimens, types of pathogens detected , and drug sensitivity of bacterial strains. Results -. The average age of the children with fungal infection was six years. The specimens were mainly from nasopharyngeal swabs. The isolation rate of Candida albicans was the highest (63. 6% ) , followed by Candida glabrata, Candida tropicalis, Candida krusei, and other Candida. The results of drug sensitive test showed that the sensitivities of Candida to amphoteriein B and 5 - fluorouracil were high. The

  8. An Integrated Approach to Anti-Cancer Drug Sensitivity Prediction.

    Science.gov (United States)

    Berlow, Noah; Haider, Saad; Wan, Qian; Geltzeiler, Mathew; Davis, Lara E; Keller, Charles; Pal, Ranadip

    2014-01-01

    A framework for design of personalized cancer therapy requires the ability to predict the sensitivity of a tumor to anticancer drugs. The predictive modeling of tumor sensitivity to anti-cancer drugs has primarily focused on generating functions that map gene expressions and genetic mutation profiles to drug sensitivity. In this paper, we present a new approach for drug sensitivity prediction and combination therapy design based on integrated functional and genomic characterizations. The modeling approach when applied to data from the Cancer Cell Line Encyclopedia shows a significant gain in prediction accuracy as compared to elastic net and random forest techniques based on genomic characterizations. Utilizing a Mouse Embryonal Rhabdomyosarcoma cell culture and a drug screen of 60 targeted drugs, we show that predictive modeling based on functional data alone can also produce high accuracy predictions. The framework also allows us to generate personalized tumor proliferation circuits to gain further insights on the individualized biological pathway.

  9. Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system

    Directory of Open Access Journals (Sweden)

    Singh Vinod

    2010-01-01

    Full Text Available Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.

  10. Sensitive neutralization test for rubella antibody.

    Science.gov (United States)

    Sato, H; Albrecht, P; Krugman, S; Ennis, F A

    1979-01-01

    A modified rubella virus plaque neutralization test for measuring rubella antibody was developed based on the potentiation of the virus-antibody complex by heterologous anti-immunoglobulin. The test is highly sensitive, yielding titers on the average 50 to 100 times higher than the haemagglutination inhibition test or the conventional plaque neutralization test. The sensitivity of this enhanced neutralization test is somewhat limited by the existence of a prozone phenomenon which precludes testing of low-titered sera below a dilution of 1:16. No prozone effect was observed with cerebrospinal fluids. The specificity of the enhanced neutralization test was determined by seroconversion of individuals receiving rubella vaccine. Although the rubella hemagglutination inhibition test remains the test of choice in routine diagnostic and surveillance work, the enhanced rubella neutralization test is particularly useful in monitoring low-level antibody in the cerebrospinal fluid in patients with neurological disorders and in certain instances of vaccine failure. PMID:107192

  11. Component resolved testing for allergic sensitization

    DEFF Research Database (Denmark)

    Skamstrup Hansen, Kirsten; Poulsen, Lars K

    2010-01-01

    Component resolved diagnostics introduces new possibilities regarding diagnosis of allergic diseases and individualized, allergen-specific treatment. Furthermore, refinement of IgE-based testing may help elucidate the correlation or lack of correlation between allergenic sensitization and allergi...

  12. Fluoroquinolones for treating tuberculosis (presumed drug-sensitive).

    Science.gov (United States)

    Ziganshina, Lilia E; Titarenko, Albina F; Davies, Geraint R

    2013-06-06

    first-line regimen. For relapse, we are uncertain if there is an effect (one trial, 170 participants, very low quality evidence). No trials reported on treatment failure. For death, sputum culture conversion at eight weeks, or serious adverse events we do not know if there was an effect (three trials, 723 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for isoniazid in standard regimens A single trial (433 participants) substituted moxifloxacin for isoniazid. Treatment failure and relapse were not reported. For death, sputum culture conversion, or serious adverse events the substitution may have little or no difference (one trial, 433 participants, low quality evidence for all three outcomes). Fluoroquinolines in four month regimensSix trials are currently in progress testing shorter regimens with fluoroquinolones. Ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin have been tested in RCTs of standard first-line regimens based on rifampicin and pyrazinamide for treating drug-sensitive TB. There is insufficient evidence to be clear whether addition or substitution of fluoroquinolones for ethambutol or isoniazid in the first-line regimen reduces death or relapse, or increases culture conversion at eight weeks. Much larger trials with fluoroquinolones in short course regimens of four months are currently in progress.

  13. Full-course drug challenge test in the diagnosis of delayed allergic reactions to penicillin

    DEFF Research Database (Denmark)

    Borch, Jakob E; Bindslev-Jensen, Carsten

    2011-01-01

    Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy.......Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy....

  14. Parametric Sensitivity Tests- European PEM Fuel Cell Stack Test Procedures

    DEFF Research Database (Denmark)

    Araya, Samuel Simon; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2014-01-01

    As fuel cells are increasingly commercialized for various applications, harmonized and industry-relevant test procedures are necessary to benchmark tests and to ensure comparability of stack performance results from different parties. This paper reports the results of parametric sensitivity tests...... performed based on test procedures proposed by a European project, Stack-Test. The sensitivity of a Nafion-based low temperature PEMFC stack’s performance to parametric changes was the main objective of the tests. Four crucial parameters for fuel cell operation were chosen; relative humidity, temperature...

  15. A Model for Random Student Drug Testing

    Science.gov (United States)

    Nelson, Judith A.; Rose, Nancy L.; Lutz, Danielle

    2011-01-01

    The purpose of this case study was to examine random student drug testing in one school district relevant to: (a) the perceptions of students participating in competitive extracurricular activities regarding drug use and abuse; (b) the attitudes and perceptions of parents, school staff, and community members regarding student drug involvement; (c)…

  16. Isolation,Identification and Drug Sensitivity Test of Clostridium perfringens%鸡产气荚膜梭菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    陈海宁; 廖申权; 戚南山; 李娟; 吕敏娜; 孙铭飞; 吴彩艳

    2013-01-01

    为确定广东韶关地区两个养殖密度较大鸡场病死鸡的患病病原,根据临床症状、剖检病变疑似坏死性肠炎,每场各分离到1株细菌,通过对细菌分离株进行形态培养、生化鉴定、牛乳汹涌发酵试验、PCR种特异性和毒素型鉴定等试验,鉴定2个分离株均为 A 型产气荚膜梭菌。对分离株进行药敏试验,测定了临床上常用的抗菌药物添加剂对两株产气荚膜梭菌的最小抑菌浓度(MIC),结果显示恩拉霉素和维吉尼亚霉素对两分离株具有良好的抑菌效果,黄霉素、吉他霉素、硫酸黏杆菌素对个别菌株具有抑菌作用,而那西肽则无明显抑菌作用。研究结果可为鸡坏死性肠炎的临床防控提供参考。%Two strains of bacteria were isolated from resembled necrotic enteritis infectious cases basing on clinical symptom and pathological lesions in two scaled chicken farms in Shaoguan area,Guang dong prov-ince.According to the bacterial morphology,biochemical properties,milk fermentation tests,species-spe-cific and toxin PCR tests,the pathogen was identified as A type Clostridium perfringens .We determined Minimum Inhibitory Concentration (MIC)of antibiotic additives used commonly for two strains.The re-sults showed that enramycin and virginiamycin had a better antibacterial effect than flavomycin,kitasamy-cin and colistin sulfate,and nosiheptide didn′t have an obvious inhibitory effect.This results may provide a guiding significance for the prevention and control of necrotic enteritis in chickens.

  17. 医院感染肠球菌的分布特点及其药敏分析%The rule of distribution and drug-sensitivity test by Enterococcus in nosocomial infection

    Institute of Scientific and Technical Information of China (English)

    王潭枫; 席云

    2009-01-01

    目的 了解医院感染肠球菌的分布特点及其药敏情况,供临床参考.方法 对2007年9月至2008年12月期间,从各临床科室送检标本中分离到的肠球菌223株进行分析与药敏实验.结果 分离到的肠球菌中,粪肠球菌和尿肠球菌分离率最高,分别是68.24%和26.61%,,分离出肠球菌最多的标本是尿液、痰和胆汁,分别是88株、45株和36株,粪肠球菌和屎肠球菌对万古霉素敏感率最高达97.48~98.38%,其次呋喃妥因和氨苄西林,敏感率在53.23~84.27%,对环沙星和氧氟沙星6种抗生素敏感率在24.50~53.22%.结论 医院感染肠球菌以泌尿道和呼吸道最为常见,感染的肠球菌对常用抗菌素耐药性高,且呈多重性耐药,并已出现对万古霉素不敏感株,应引起关注.%Objective To investigate and find the rule of site distribution by Enterococcus in nosocomial infection,and the offer the referrence to clinic.Methods 223 Enterococcus strains were different infection specimens in the hospital from September 2007 to December 2008 were analyzed and performed the drug-sensitivity test.Results In the 223 isolated Enterococcus strains,the isolation rates of E.faecalis and E.faecium were 68.24% and 26.61%.The specimen type with most isolation rates of Enterococcus were urine,sputum and bile,with the number 88 strains,45 strains and 36 strains.In the drug-sensitivity test,E.faecalis and E.faecium were sensitized to,with the rate from 97.48% to 98.38%.The drug-susceptibility rates of Enterococcus to nitrofurantoin and ampicillin were from 53.23% to 84.27%.The drug-susceptibility rates of Enterococcus to ciprofloxacin and Ofloxacin were from 24.50% to 53.22%.Conclusion Enterococcus isolated from nosocomial infection were heavily resistanted to antibiotics and multi-drug resistant.And some Enterococcus strains became resistanted to vancomycin.All above should be paid more attention to.

  18. Study of sensitivity test to neisseria gonorrhoeae antibiotic drug in NanTong district%南通地区2006~2008年淋球菌耐药性分析

    Institute of Scientific and Technical Information of China (English)

    孙亚军; 袁建芬; 喻海忠

    2009-01-01

    Objective To explore the sensitivity of Neisseria Gonorrhoea in Nantong to antibiotic remedy.Methods To select and identify 147 cases of Neisseria Gonorrhoeae specimens.Then drug sensitivity test was carried out through making five sorts of antibiotics.Results Of all the 3 antibiotic agents,the higher resistances to Neisseria Gonorrhoeae were penicillin,acheomycin, ciprofloxacin in turn,the percentages of resistance were 72.10%,68.08% and 8.85% respectively.On the other hand,the higher susceptibilities to Neisseria Gonorrhoeae were ceftriaxone and spectinomycin the percentages of susceptibility were 100% and 94.56% respectively.Conclusion Ceftriaxone and spectinomycin can still be used as primary agents to cure the disease like Neisseria Gonorrhoeae specimens in Nantong,but clinical doctors need to pay more attention to the fact that resistant strains to spectinomycin have come into existence.The result suggests that these antibiotics may be used under guidance of drug sensitivity test in clinic .%目的 探讨南通地区淋病奈瑟菌(NG) 对抗菌药物的敏感性.方法 选择147株NG标本进行菌株鉴定和5种抗菌药物的敏感试验.结果 NG对青霉素、四环素及环丙沙星的耐药率分别为72.10%、68.08%和8.85%,NG对菌必治(头孢三嗪)、壮观霉素的敏感率为100.00%、94.56%.结论 菌必治(头孢三嗪)和壮观霉素仍可作为南通地区淋病治疗的首选药物,但淋球菌对壮观霉素已出现耐药株,应引起临床医生的高度警惕;建议临床应在药敏试验的指导下用药.

  19. Visual contrast sensitivity in drug-induced Parkinsonism.

    Science.gov (United States)

    Bulens, C; Meerwaldt, J D; van der Wildt, G J; Keemink, C J

    1989-03-01

    The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way.

  20. Visual contrast sensitivity in drug-induced Parkinsonism.

    Science.gov (United States)

    Bulens, C; Meerwaldt, J D; van der Wildt, G J; Keemink, C J

    1989-01-01

    The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way. PMID:2926418

  1. Patch testing for adverse drug reactions.

    Science.gov (United States)

    Sekhon, Sahil; Nedorost, Susan T

    2017-01-01

    Adverse drug reactions result in a substantial number of hospital admissions and inpatient events. Diagnosis usually is made with clinical judgment and circumstantiality without diagnostic testing. Furthermore, even in situations where diagnostic testing is performed, no safe gold standard tests exist. Oral rechallenge is currently the gold standard but carries the risk of recrudescence of severe allergic symptoms. Other tests include skin prick tests, the lymphocyte transformation test, immunohistochemistry, and patch testing. This article provides a review of patch testing in cases of adverse drug reactions and presents new data on this topic.

  2. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  3. Drug susceptibility testing of nontuberculous mycobacteria

    NARCIS (Netherlands)

    Ingen, J. van; Kuijper, E.J.

    2014-01-01

    Diseases caused by nontuberculous mycobacteria are emerging in many settings. With an increased number of patients needing treatment, the role of drug susceptibility testing is again in the spotlight. This articles covers the history and methodology of drug susceptibility tests for nontuberculous

  4. Society of Hair Testing guidelines for drug testing in hair.

    Science.gov (United States)

    Cooper, Gail A A; Kronstrand, Robert; Kintz, Pascal

    2012-05-10

    The Society of Hair Testing (SoHT) Guidelines for Drug Testing in Hair provide laboratories with recommended best practice guidelines whether they are currently offering drug testing in hair, or plan to offer a hair testing service in the future. The guidelines include reference to recommended sample collection and storage procedures, through sample preparation, pre-treatment and analysis and the use of cut-offs.

  5. Workplace drug testing in Italy - critical considerations.

    Science.gov (United States)

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; Pozzi, Fulvia; Collo, Giancarlo; Groppi, Angelo

    2013-04-01

    Workplace drug testing (WDT) was established in Italy on 30 October 2007. Two tiers of survey are required: the first tier concerns drug testing on urine samples, the second involves both urine and hair analysis. Between July 2008 and December 2011, 10 598 workers' urine samples and 72 hair samples for opiates, cocaine, cannabinoids, amphetamines, methylenedioxyamphetamines, methadone, and buprenorphine were tested in our laboratory. Urine analyses were performed by immunological screening (EMIT); hair analysis and confirmation tests in urine were performed by gas chromatography-mass spectrometry (GC-MS). Employees tested positive in urine for drugs of abuse numbered 2.8% in 2008, 2.03% in 2009, 1.62% in 2010, and 1.43% in 2011. As regards the second level of analysis, we observed that only one-third of the workers who had been tested positive for drugs of abuse were referred to an Addiction Treatment Unit in order to verify drug addiction. Our experience shows that, four years after approval of the law on WDT, the percentage of workers positive for drugs of abuse in urine has reduced in comparison to the first year. Moreover, our data show that most of the times employees who tested positive are tardily referred or not referred at all to a Public Addiction Treatment Unit to verify drug addiction. This makes us believe that the legal provisions are widely disregarded not paying the right tribute to the fact that Italy is one of few European countries with legislation on WDT.

  6. Biological studies of matrix metalloproteinase sensitive drug delivery systems

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann

    due to severe side effects as a result of drug distribution to healthy tissues. To enhance ecacy of treatment and improve life quality of patients, tumor specific drug delivery strategies, such as liposome encapsulated drugs, which accumulate in tumor tissue, has gained increased attention. Several...... for delivery of drugs to specific tissues or cells utilizing biological knowledge of cancer tissue is getting increased attention. In this thesis a novel matrix metalloproteinase-2 (MMP-2) sensitive poly-ethylene glycol (PEG) coated liposomal drug delivery system for treatment of cancer was developed...... the use of MMP- 2 as a trigger for liposomal activation in tumor tissue. Thus, this new strategy provides a promising system for specific delivery of encapsulated drugs and controlled release in tumor tissues, resulting in enhanced drug bioavailability and decreased systemic side effects. In addition, we...

  7. Acid-Sensitive Magnetic Nanoparticles as Potential Drug Depots.

    Science.gov (United States)

    Wuang, Shy Chyi; Neoh, Koon Gee; Kang, En-Tang; Leckband, Deborah E; Pack, Daniel W

    2011-06-01

    Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH-sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Because of the released drug, the particles were found to be cytotoxic to human breast cancer cells in vitro. Such magnetic nanoparticles, with the potential to retain drug under physiological conditions and release the drug in conditions where the pH is lower or temperature is higher, may be useful in magnetic drug targeting by reducing the side effects of the drug caused to healthy tissues. In addition, they may serve as hyperthermia agents where the high temperatures used in hyperthermia can trigger further drug release.

  8. Hair Testing for Drugs of Abuse

    OpenAIRE

    Karačić, Višnja; Skender, Ljiljana

    2003-01-01

    Hair testing for drugs of abuse is a developing technology, which offers the possibility of longer detection times than is commonly obtained with urine analysis. It is the main method for evaluation of an individual’s drugs of abuse history. In many countries hair analysis is routinely used to detect drug abuse in forensic cases, occupational and traffic medicine and clinical toxicology. Hair analysis in pregnant women, neonates and infants is a useful tool for the detection of...

  9. Component resolved testing for allergic sensitization

    DEFF Research Database (Denmark)

    Skamstrup Hansen, Kirsten; Poulsen, Lars K

    2010-01-01

    disease. Novel tools to predict severe outcomes and to plan for allergen-specific treatment are necessary, and because only a small amount of blood is needed to test for a multitude of allergens and allergenic components, component resolved diagnostics is promising. A drawback is the risk of overdiagnosis......Component resolved diagnostics introduces new possibilities regarding diagnosis of allergic diseases and individualized, allergen-specific treatment. Furthermore, refinement of IgE-based testing may help elucidate the correlation or lack of correlation between allergenic sensitization and allergic...... and misinterpretation of the complex results of such tests. Also, the practical use and selection of allergenic components need to be evaluated in large studies including well-characterized patients and healthy, sensitized controls and with representation of different geographical regions....

  10. Isolation, Identification and Drug Sensitive Test of Aeromonas jandaei from Tilapia (Tilapia nilotica)%罗非鱼(Tilapia nilotica)简达气单胞菌病的病原分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    杨宁; 姜芳燕; 黄海; 焦健

    2015-01-01

    Tilapia is a very important freshwater aquacultural species in China; however, bacterial disease caused huge economic losses in recent years with the continous expansion of tilapia aquaculture. The aim of this research was to isolate, identify, and test drug sensitivity of bacteria pathogen found in diseased Tilapia nilotica. Six bacteria were isolated from diseased T. nilotica as suspected pathogenic bacteria. The bacteria (NL05) isolated from intestine of diseased T. nilotica was determined as pathogenic bacteria by infection experiment. The LD50 was 1×103 CFU/g. Bacteria NL05 was identified as Aeromonas jandaei. Morphology observation indicated that NL05 was gram-negative, rod-shaped. Thirteen physiological and biochemical indexes were positive including maltose, mannitol, glucose, salicin, and hydrogen sulfide. Ten indexes were negative including saccharum, arabinose, xylose, inositol, and dulcitol. There was 1442 bp in the sequence of 16S rRNA, which was submitted into GenBank (Accession number: KC916744). The phylogenetic tree based on 16S rRNA showed that NL05 was A. jandaei. Drug sensitivity test indicated that NL05 was sensitive to 13 antibiotics including ofloxacin, ciprofloxacin, amikacin, polymyxin B, norfloxacin, rifampicin, and lincomycin, and intermediate sensitive to 5 antibiotics including azithromycin, ceftriaxone, kanamycin, streptomycin and minocycline, and resistant to 13 antibiotics including ampicillin, amoxicillin, enrofloxacin, sulfamethoxazole, and trimethoprim. The results will provide references for the prevention and treatment of diseases caused by T. nilotica.%从患病罗非鱼(Tilapia nilotica)体内分离得到细菌 NL05,通过回归感染试验确定 NL05为致病菌,并测出 NL05对罗非鱼的半致死量(LD50)为1×103 CFU/g。结合细菌形态学特征、生理生化指标和16S rRNA 基因同源分析,鉴定 NL05为简达气单胞菌(Aeromonas jandaei)。形态学观察发现, NL05为革兰氏阴性、短杆状;

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

    Directory of Open Access Journals (Sweden)

    Bilge Bülbül Şen

    2013-03-01

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

  12. 20例感染性心内膜炎病原菌及耐药性分析%Pathogenic Bacteria Distribution in 20 Cases with Infective Endocarditis and their Drug Sensitivity Test Results

    Institute of Scientific and Technical Information of China (English)

    熊祝嘉; 岳志刚; 李小瑛

    2013-01-01

    目的 通过对20例感染性心内膜炎患者的培养结果进行回顾性研究,为临床合理使用抗生素提供依据.方法 回顾性分析煤炭总医院2010年20例感染性心内膜炎病原菌的分布及其对抗生素的敏感性.结果 革兰阳性球菌19株,占到95%,其中链球菌9株(占45%),主要为化脓性链球菌;葡萄球菌7株(占35%),主要为金黄色葡萄球菌;肠球菌3株(占15%),均为屎肠球菌.此外大肠埃希菌检出1株(占5%).不同的病原菌有其自身的耐药特点,金黄色葡萄球菌的耐药较严重,所有阳性菌对万古霉素敏感.结论 感染性心内膜炎病原菌以链球菌为主.不同的病原菌有其自身的耐药特点,对感染性心内膜炎患者应及早进行细菌培养和耐药检测,以指导临床正确用药,防止耐药株的出现.%Objective To detect the distribution of pathogenic bacteria in 20 cases with infective endocarditis and their resistance to antimicrobial drugs, and to provide the reference for selecting antimicrobial drugs rationally in clinical treatment. Methods To analysis the pathogenic bacteria distribution and their sensitivity to antibiotics from 20 cases with infective endocarditis conformed by bacterial culture. Results The proportion of Gram-positive cocco bacterium was 95% (Streptococcus account for 45% ,the most was Streptococcus pyogenes; Staphylococcus account for 35% ,the most was Staphylococcus aureus; Enterococ-cus account for 15% ,all was Enterococcus faecium) ;the proportion of Gram-necgative bacillus was 5% ( Escherichia coli). Different pathogens had its own characteristics of resistance, and the drug resistance of staphylococcus aureus was serious. The Gram-positive cocco bacterium were found to be all sensitive to vancomycin. Conclusion Streptococcus is still the primary pathogen among patients with Infective Endocarditis. Different pathogens had its own characteristics of resistance, and we should carry out cultivation

  13. 黄喉拟水龟白眼病病原菌分离鉴定及药敏试验%Isolation, identification and drug sensitivity test of pathogen causing withe eye disease of Mauremys mutica

    Institute of Scientific and Technical Information of China (English)

    陆专灵; 钟一治; 赵忠添; 雷燕; 韦友传; 张益峰

    2016-01-01

    【目的】明确黄喉拟水龟白眼病的病原菌及其药敏特性,为该病的防控提供参考依据。【方法】对患白眼病的黄喉拟水龟进行无菌解剖、划线培养、分离筛选,对分离获得的菌株进行培养特征、生理生化特性鉴定、16S rDNA序列分析及同源性比对分析,通过动物致病性试验鉴定致病性,并采用药敏试验检验其耐药性。【结果】从患白眼病黄喉拟水龟稚龟肝脏、肺脏及脾脏中分离获得的优势菌株对小白鼠和黄喉拟水龟均有强的致病性,为兼性厌氧、产酸、产气、发酵型、无运动能力的革兰氏阴性杆菌,其16S rDNA序列(GenBank登录号KU855372)与肺炎克雷伯菌(Klebsiella pneumoniae)的同源性达99.1%。分离菌株对恩诺沙星、头孢噻吩、头孢噻肟、氧氟沙星等高度敏感,但对链霉素、新霉素、青霉素、卡那霉素、四环素、克林霉素、强力霉素、阿莫西林、复方新诺明等已产生耐药性。【结论】肺炎克雷伯菌是引起黄喉拟水龟白眼病的主要病原菌,生产中可选用恩诺沙星、氧氟沙星等沙星类或头孢噻吩、头孢噻肟等头孢类药物进行防治。%Objective]Pathogen of withe eye disease in Mauremys mutica and its drug sensitivity characteristics were confirmed in order to provide reference for prevention and control of the disease. [Method]Sterile anatomy, streak cul-ture, isolation and selection were applied on M. muticas with withe eye disease. Cultural characteristics and physiological and biochemical characteristics of the isolated strains were identified, 16S rDNA sequence analysis and homology compar-ison were conducted. Pathogenicity was identified through animal pathogenic experiment and drug resistance was identified through drug sensitivity test. [Result]A dominant strain was isolated from liver, lung and spleen of M. mutica with withe eye disease, which was strongly pathogenic to mice and M

  14. Multitask learning improves prediction of cancer drug sensitivity

    Science.gov (United States)

    Yuan, Han; Paskov, Ivan; Paskov, Hristo; González, Alvaro J.; Leslie, Christina S.

    2016-01-01

    Precision oncology seeks to predict the best therapeutic option for individual patients based on the molecular characteristics of their tumors. To assess the preclinical feasibility of drug sensitivity prediction, several studies have measured drug responses for cytotoxic and targeted therapies across large collections of genomically and transcriptomically characterized cancer cell lines and trained predictive models using standard methods like elastic net regression. Here we use existing drug response data sets to demonstrate that multitask learning across drugs strongly improves the accuracy and interpretability of drug prediction models. Our method uses trace norm regularization with a highly efficient ADMM (alternating direction method of multipliers) optimization algorithm that readily scales to large data sets. We anticipate that our approach will enhance efforts to exploit growing drug response compendia in order to advance personalized therapy. PMID:27550087

  15. Results of culture of bacteria in semen from infertile males and drug sensitivity test%男性不育患者精液病原菌分离及其药敏分析

    Institute of Scientific and Technical Information of China (English)

    穆小萍; 张德纯; 邓文喻; 赖卫明; 柏彩英

    2011-01-01

    Aim To understand the distribution and drug resistance of pabacteria in semen sample from infertile males.Methods There 2 316 semen samples from infertile males collected from August 2009 to July 2010 were cultured and isolated pure strains were identified and their drug drug resistance was tested by VITEK-2 automicroscan.Results Among the 2 316 semen samples,229 were infected with bacteria.The total detection rate was 9.89%.The infection of G+ bacteria accounted for 61.6%, whereas G- bacteria was 37.1%.The percentage of E.coli the highest (21.4%), the second was Streptococcus agalactiae ( 17.5% ) ,and the third is Enterococcus faccalis ( 13.5% ).There were 10 E.coli strains producing ESBL (20%).The antibiotic resistance of Streptococcus agalactiae and Enterococcus faecalis to erythromycin and tetracycline were higher (>50%).Conclusion Gram-positive cocci was the main pathogens isolated in semen samples of infertile males.It was important for clinical selection of antibiotics rationally according to drug sensitivity test%目的 了解本地区男性不育患者生殖道感染细菌的分布特点和耐药情况,为临床治疗提供参考.方法 对2009年8月~2010年7月我院生殖健康科送检的2316份男性不育患者精液标本进行细菌培养,并以法国梅里埃的全自动细菌鉴定药敏系统(VITEK-2 compact)对分离出的纯菌株进行鉴定和药敏试验.结果 2316份标本中229份分离出细菌229株,均为每例单一菌株,总检出率为9.89%,其中G+菌141株,占沾61.6%,G-菌85株,占37.1%,真菌3株,占1-3%.排名前三位的病原菌分别是大肠埃希茵(21.4%)、无乳链球菌(17.5%)、粪肠球菌(13.5%);大肠埃希茵产超广谱β-内酰胺酶的有10株(20%),无乳链球菌和粪肠球菌对红霉素和四环素耐药率较高(>50%).结论男性不育患者精液细菌感染的菌种分布以革兰阳性球菌为主,治疗用抗生素应根据药敏试验结果合理选用,是减少耐药菌株产生的必要手段.

  16. Improving Drug Sensitivity Prediction Using Different Types of Data

    OpenAIRE

    Hejase, HA; Chan, C.

    2015-01-01

    The algorithms and models used to address the two subchallenges that are part of the NCI-DREAM (Dialogue for Reverse Engineering Assessments and Methods) Drug Sensitivity Prediction Challenge (2012) are presented. In subchallenge 1, a bidirectional search algorithm is introduced and optimized using an ensemble scheme and a nonlinear support vector machine (SVM) is then applied to predict the effects of the drug compounds on breast cancer cell lines. In subchallenge 2, a weighted Euclidean dis...

  17. In vitro tests for drug hypersensitivity reactions : an ENDA/EAACI Drug Allergy Interest Group position paper

    NARCIS (Netherlands)

    Mayorga, C.; Celik, G.; Rouzaire, P.; Whitaker, P.; Bonadonna, P.; Rodrigues-Cernadas, J.; Vultaggio, A.; Brockow, K.; Caubet, J. C.; Makowska, J.; Nakonechna, A.; Romano, A.; Montanez, M. I.; Laguna, J. J.; Zanoni, G.; Gueant, J. L.; Oude Elberink, H.; Fernandez, J.; Viel, S.; Demoly, P.; Torres, M. J.

    2016-01-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because invivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation test

  18. 49 CFR 199.105 - Drug tests required.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing... a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any... likely that a drug test would reveal whether the performance was affected by drug use. (c) Random testing...

  19. Improving Drug Sensitivity Prediction Using Different Types of Data.

    Science.gov (United States)

    Hejase, H A; Chan, C

    2015-02-01

    The algorithms and models used to address the two subchallenges that are part of the NCI-DREAM (Dialogue for Reverse Engineering Assessments and Methods) Drug Sensitivity Prediction Challenge (2012) are presented. In subchallenge 1, a bidirectional search algorithm is introduced and optimized using an ensemble scheme and a nonlinear support vector machine (SVM) is then applied to predict the effects of the drug compounds on breast cancer cell lines. In subchallenge 2, a weighted Euclidean distance method is introduced to predict and rank the drug combinations from the most to the least effective in reducing the viability of a diffuse large B-cell lymphoma (DLBCL) cell line.

  20. Testing drug additivity based on monotherapies.

    Science.gov (United States)

    Yang, Harry; Novick, Steven J; Zhao, Wei

    2015-01-01

    Under the Loewe additivity, constant relative potency between two drugs is a sufficient condition for the two drugs to be additive. Implicit in this condition is that one drug acts like a dilution of the other. Geometrically, it means that the dose-response curve of one drug is a copy of another that is shifted horizontally by a constant over the log-dose axis. Such phenomenon is often referred to as parallelism. Thus, testing drug additivity is equivalent to the demonstration of parallelism between two dose-response curves. Current methods used for testing parallelism are usually based on significance tests for differences between parameters in the dose-response curves of the monotherapies. A p-value of less than 0.05 is indicative of non-parallelism. The p-value-based methods, however, may be fundamentally flawed because an increase in either sample size or precision of the assay used to measure drug effect may result in more frequent rejection of parallel lines for a trivial difference. Moreover, similarity (difference) between model parameters does not necessarily translate into the similarity (difference) between the two response curves. As a result, a test may conclude that the model parameters are similar (different), yet there is little assurance on the similarity between the two dose-response curves. In this paper, we introduce a Bayesian approach to directly test the hypothesis that the two drugs have a constant relative potency. An important utility of our proposed method is in aiding go/no-go decisions concerning two drug combination studies. It is illustrated with both a simulated example and a real-life example. Copyright © 2015 John Wiley & Sons, Ltd.

  1. 1530例女性生殖道支原体感染及药敏试验分析%The analysis on female genital tract specimens mycoplasma infection and drug sensitivity test in 1 530 cases

    Institute of Scientific and Technical Information of China (English)

    邱晓芳

    2015-01-01

    Objective To investigate the positive rate of female genital tract specimens mycoplasma infection and drug susceptibility to assist clinical rational drug use.Methods Mycoplasma culture and drug susceptibility test were performed in 1 530 female outpatients in Women's and Children's Center Hospital of Chengdu City from Nov 2013 to Oct 2014.All cases were divided into different groups on the basis of clinical information, positive rate of mycoplasma infection and drug susceptibility for each group were analyzed.Results In 1 530 cases of female genital tract secretions sample test, mycoplasma infection were positive in 650 cases ( 42.5%) .Sensitive rates of mycoplasma to tetracycline, doxycycline, josamycin, mincycline and clarithromycin were high ( all above 98 %), followed by rom erythromycin (84.6 %), while ofloxacin (19.2 %), azithromycin (18.8 %), sparfloxacin (11.5 %), levofloxacin (4.31 %) were with high drug resistance rate of mycoplasma.In different groups of genital tract secretions samples, the positive rates of mycoplasma detection and the drug resistance rates had statistically differences ( P<0.05 ) .Conclusion Overall positive rate of the mycoplasma infection is high in gynecologic patients, and the positive rate and drug resistance rate differ between groups.For women of childbearing age who have no obvious self-conscious symptoms, mycoplasma screening can be more scientific, more timely to guide the clinical treatment and prenatal care which promotes eugenics.%目的:探讨女性生殖道支原体感染检测的阳性率和药敏情况,以辅助临床合理用药。方法对2013年11月至2014年10月成都市妇女儿童中心医院门诊就诊的1530例女性生殖道分泌物进行支原体培养及体外药敏试验。依据临床信息,将其进行分组,对各组支原体检测阳性率和药敏试验结果进行分析。结果1530例女性生殖道分泌物标本的检测结果中,支原体检测结果阳性650例(42.5

  2. The Drug Sensitivity of Cyclosporine A Combined with Antineoplastic Drugs in Retinoblastoma in Vitro

    Institute of Scientific and Technical Information of China (English)

    Wanli Liu; Zhongyao Wu

    2005-01-01

    Purpose: To study cyclosporine A inhibition on the fresh retinoblastoma cells in vitro and increasing the drug sensitivity after combined with different antineoplastic drugs.Methods: To study the growth curve of cyclosporine A on 27 samples of primary retinoblastoma cells by MTT assay and to study the change of the drug sensitivity by cyclosporine A combined with seven antineoplastic drugs.Results: The average IC50 of cyclosporine A on the 27 retinoblastoma cells is 67.81μg/ml and the average inhibitive rate of these samples is 26.1% when cyclosporine A is in the concentration of 2μg/ml. The inhibitive rates all got improved after the seven antineoplastic drugs combined with cyclosporine A and the increasing average inhibitive rate is more than 5.Conclusion: Cyclosporine A can inhibit retinoblastoma cells in vitro and its inhibitive effect is dose dependent. Moreover it can enhance the inhibition of multiple antineoplastic drugs on retinoblastoma cells.

  3. Co-treatment with the anti-malarial drugs mefloquine and primaquine highly sensitizes drug-resistant cancer cells by increasing P-gp inhibition.

    Science.gov (United States)

    Kim, Ju-Hwa; Choi, Ae-Ran; Kim, Yong Kee; Yoon, Sungpil

    2013-11-22

    The purpose of this study was to identify conditions that will increase the sensitivity of resistant cancer cells to anti-mitotic drugs. Currently, atovaquine (ATO), chloroquine (CHL), primaquine (PRI), mefloquine (MEF), artesunate (ART), and doxycycline (DOY) are the most commonly used anti-malarial drugs. Herein, we tested whether anti-malarial drugs can sensitize drug-resistant KBV20C cancer cells. None of the six tested anti-malarial drugs was found to better sensitize the drug-resistant cells compared to the sensitive KB cells. With an exception of DOY, all other anti-malarial drugs tested could sensitize both KB and KBV20C cells to a similar extent, suggesting that anti-malarial drugs could be used for sensitive as well as resistant cancer cells. Furthermore, we examined the effects of anti-malarial drugs in combination with an antimitotic drug, vinblastine (VIN) on the sensitisation of resistant KBV20C cells. Using viability assay, microscopic observation, assessment of cleaved PARP, and Hoechst staining, we identified that two anti-malarial drugs, PRI and MEF, highly sensitized KBV20C-resistant cells to VIN treatment. Moreover, PRI- or MEF-induced sensitisation was not observed in VIN-treated sensitive KB parent cells, suggesting that the observed effect is specific to resistant cancer cells. We demonstrated that the PRI and MEF sensitisation mechanism mainly depends on the inhibition of p-glycoprotein (P-gp). Our findings may contribute to the development of anti-malarial drug-based combination therapies for patients resistant to anti-mitotic drugs.

  4. Results of workplace drug testing in Norway

    Directory of Open Access Journals (Sweden)

    Hilde Marie Erøy Lund

    2011-12-01

    Full Text Available Workplace drug testing is less common in Norway than in many other countries. During the period from 2000-2006, 13469 urine or blood samples from employees in the offshore industry, shipping companies and aviation industry were submitted to the Norwegian Institute of Public Health for drug testing. The samples were analysed for benzodiazepines, illicit drugs, muscle relaxants with sedating properties, opioids and z-hypnotics. In total, 2.9% of the samples were positive for one or more substances. During the study period the prevalence decreased for morphine (from 1.9% to 1.1% and increased for amphetamine (from 0.04% to 0.6%, clonazepam (from 0% to 0.1%, methamphetamine (from 0.04% to 0.6%, nitrazepam (from 0% to 0.4% and oxazepam (from 0.5% to 1.3% (p<0.05. There was no significant change in prevalence for the other substances included in the analytical programme. Illicit drugs were significantly associated with lower age (OR: 0.93, p<0.05. This study found low prevalence of drugs among employees in companies with workplace drug testing programmes in Norway.

  5. Drug Testing. ERIC Digest Series Number EA 35.

    Science.gov (United States)

    Klauke, Amy

    The issue of drug testing is the focus of this ERIC Digest. Several aspects of drug testing discussed in question-and-answer format: (1) What is the current status of drug use in the schools? (2) What legal questions arise when schools consider drug testing? (3) How might drug testing be applied in a fair, economical, and legally safe manner? (4)…

  6. Echinodermata in ecotoxicological tests: maintenance and sensitivity

    Directory of Open Access Journals (Sweden)

    Jocássio Batista Soares

    2016-03-01

    Full Text Available Abstract This work investigates the sensitivity of four species of Echinodermata (Lytechinus variegatus, Echinometra lucunter, Arbacia lixula and Encope emarginata, evaluating the effect of five reference toxicants (Cd, Pb, Cr, Cu and SDS on embryo-larval development, following the official protocols. It also evaluates techniques for the maintenance of L. variegatus in the laboratory, changes in its sensitivity, and the effects of chemical agents that induce the release of gametes, on the survival rates of the organisms. In terms of the maintenance of L. variegatus in the laboratory, the diet with vegetable content appears to be more favorable for maintenance and maturation in cultivation tanks. Chemical inducers such as KCl and the Anesthetic (lidocaine and epinephrine resulted in high adult mortality rates, discouraging its re-induction. The tests performed with different species of sea urchin and sand dollar, using different reference toxicants, showed no variations in sensitivity to the more toxic chemicals, indicating that different species can be used for evaluation and environmental impact assessment.

  7. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  8. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  9. The Pathogen Diagnosis and Drug Sensitivity Test of Swollen Eye Chicken from Qingyuan City%清远市肿眼肉鸡病原诊断和药敏试验

    Institute of Scientific and Technical Information of China (English)

    许华; 蒋梦娇; 陈超; 张成; 颜亨梅; 江宇轩; 刘佳馨; 阮晓慧; 陈梓煌

    2012-01-01

    广东省清远地区3群肉鸡临床表现不同程度的肿眼、流鼻水等症状,临床治疗处理效果不理想.在3群病鸡中各取病鸡鼻窦腔分泌液进行细菌分离培养、革兰氏和瑞氏染色,并对分离菌株进行了玻片凝集和生化试验.结果表明,革兰氏染色呈阴性,瑞氏染色呈蓝色,油镜下可见细菌呈短杆菌或球杆菌,两极着色,3群分离株均与副鸡嗜血杆菌A型血清完全凝集反应,与B和C型血清无凝集反应,确定肿眼肉鸡病原为A型副鸡嗜血杆菌.同时选用多种药物研究了该病原菌的药敏性,结果显示,A型副鸡嗜血杆菌对头孢噻呋、氟苯尼考和青霉素3种药物均表现极敏.%Different clinical symptoms of swollen eye and runny nose were shown on three groups of chicken in Qingyuan district, Guangdong Province and ideal clinical treatment result had not achieved. In order to detect the pathogen of these three groups of chickens, bacterial isolation and culture, gram staining and wright stain were performed on nasal fluids taken from them as well as biochemical and slide agglutination tests on relevant isolated bacterial strains. The results showed that the bacteria were gram negative and blue for wright stain, showed the shape of bacilli or cocci under oil immersion objective, bipole stained, could strongly agglutinate with Haemophilus paragallinarum (HPG) serotype A serum but not with serotype B or C serum. Consequenty, the pathogen of this swollen eye chicken was identified as HPG serotype A. Drug sensitivity test was carried out simultaneously on this pathogen and showed that HPG serotype A was super hypersensitive to cef-tiofur, florfenicol and penicillin.

  10. 利用鼠尾胶原建立胶原微滴药物敏感性检测方法%Establishing the method of collagen-gel droplet embedded culture drug sensitivity test with rat tail collagen

    Institute of Scientific and Technical Information of China (English)

    胡亚; 周涛; 廖泉; 张太平; 陈革; 赵玉沛

    2008-01-01

    Objective To explore the clinical application of collagen-gel droplet embedded-culture drug sensitivity test(CD-DST)in the malignant tumors.Methods CD-DST was established with rat tail collagen.Three pancreatic cancer cell lines,surgical resection specimens including 15 cases of pancreatic cancer and 10 cases of gastrointestinal cancer were examined using CD-DST.Results The overall achievement ratio of CD-DST for clinical tumor specimens was 80%(20/25).In vitro chemosensitivities of pancreatic carcinoma cells to 5-FU,gemcitabine and oxaliplatin were lower than those of gastrointestinal carcinoma.Conclusions CD-DST with rat tail collagen is a valuable chemosensitivity testing method for malignant tumors.It can be used to realize individualized anticancer chemotherapy.%目的 利用鼠尾胶原建立胶原凝胶微滴肿瘤药物敏感性检测(CD-DST)技术,探讨其在胰腺瘤等恶性肿瘤化疗敏感性检测中的应用.方法 利用鼠尾胶原建立CD-DST检测方法 ,对3株胰腺癌细胞株、15例胰腺癌和10例胃肠道恶性肿瘤的手术切除标本进行临床化疗药物敏感性检测.结果 利用鼠尾胶原建立的CD-DST能有效的对胰腺癌细胞株和临床肿瘤标本进行体外肿瘤药物敏感性检测,对临床肿瘤标本的整体检测成功率为80%(20/25),胰腺癌细胞在体外对5-氟尿嘧啶、吉西他滨、奥沙利铂的化疗敏感性低于胃肠道恶性肿瘤.结论 CD-DST是一种切实可行的体外肿瘤化疗药物敏感性检测方法 ,可用于临床制定个体化化疗方案.

  11. Human sports drug testing by mass spectrometry.

    Science.gov (United States)

    Schänzer, Wilhelm; Thevis, Mario

    2017-01-01

    Since the installation of anti-doping rules and regulations and their international enforcement in the mid-1960s, mass spectrometry has been an integral part of doping control procedures. Although its utility was limited in the first decade, instrumental improvements and method optimizations have made mass spectrometry, in all its facets, an indispensable tool in modern sports drug testing. In this review, milestones in doping control analysis accomplished in Germany and reaching from the early developments to the current use of hyphenated mass spectrometric techniques concerning low- and high molecular mass analytes are presented. The considered drug classes include anabolic agents, peptidic drugs, nucleotide-derived therapeutics, approved and non-approved organic as well as inorganic analytes, and particular focus is put on drug class- and instrument-driven strategies. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:16-46, 2017.

  12. Different combination of drugs regarding the damage on organs targeting salt sensitivity or non-salt-sensitive hypertension

    Institute of Scientific and Technical Information of China (English)

    吴琪

    2013-01-01

    Objective To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination.Methods 120 hypertensive patients including 60 cases salt-sensitive(SS)

  13. 14 CFR 120.117 - Implementing a drug testing program.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Implementing a drug testing program. 120... AND ALCOHOL TESTING PROGRAM Drug Testing Program Requirements § 120.117 Implementing a drug testing.... (4) A part 145 certificate holder who has your own drug testing program Obtain an Antidrug and...

  14. 46 CFR 16.113 - Chemical drug testing.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... testing programs required by this part must use only drug testing laboratories certified by the Department...

  15. HIV-1 drug resistance and resistance testing.

    Science.gov (United States)

    Clutter, Dana S; Jordan, Michael R; Bertagnolio, Silvia; Shafer, Robert W

    2016-12-01

    The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases. Copyright © 2016 Elsevier B

  16. Triclosan Derivatives: Towards Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Freundlich, Joel S.; Wang, Feng; Vilchèze, Catherine; Gulten, Gulcin; Langley, Robert; Schiehser, Guy A.; Jacobus, David P.; Jacobs, Jr., William R.; Sacchettini, James C.; (Einstein); (TAM); (Jacobus)

    2009-06-30

    Isoniazid (INH) is a frontline antitubercular drug that inhibits the enoyl acyl carrier protein reductase InhA. Novel inhibitors of InhA that are not cross-resistant to INH represent a significant goal in antitubercular chemotherapy. The design, synthesis, and biological activity of a series of triclosan-based inhibitors is reported, including their promising efficacy against INH-resistant strains of M. tuberculosis. Triclosan has been previously shown to inhibit InhA, an essential enoyl acyl carrier protein reductase involved in mycolic acid biosynthesis, the inhibition of which leads to the lysis of Mycobacterium tuberculosis. Using a structure-based drug design approach, a series of 5-substituted triclosan derivatives was developed. Two groups of derivatives with alkyl and aryl substituents, respectively, were identified with dramatically enhanced potency against purified InhA. The most efficacious inhibitor displayed an IC{sub 50} value of 21 nM, which was 50-fold more potent than triclosan. X-ray crystal structures of InhA in complex with four triclosan derivatives revealed the structural basis for the inhibitory activity. Six selected triclosan derivatives were tested against isoniazid-sensitive and resistant strains of M. tuberculosis. Among those, the best inhibitor had an MIC value of 4.7 {mu}g mL{sup -1} (13 {mu}M), which represents a tenfold improvement over the bacteriocidal activity of triclosan. A subset of these triclosan analogues was more potent than isoniazid against two isoniazid-resistant M. tuberculosis strains, demonstrating the significant potential for structure-based design in the development of next generation antitubercular drugs.

  17. Ethical considerations in urine drug testing.

    Science.gov (United States)

    Passik, Steven D; Kirsh, Kenneth L

    2011-01-01

    Recent passage of a House Bill in the state of Washington led to a commentary on whether mandates for urine drug testing of pain patients represented a breach of the Fourth and Fourteenth Amendment rights of patients. Issues over true consent to such tests and potential view of warrantless searches were discussed. The authors address these concerns in a broader context of risk management and stratification efforts, along with discussion about the need for a tailored approach in this arena and consideration of cost burden for such tests. Finally, the argument is made that social justice issues need to be considered (along with issues of autonomy, beneficence, and nonmaleficence).

  18. 49 CFR 199.109 - Review of drug testing results.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  19. 75 FR 76078 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-12-07

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY... percentage rate for random drug testing. SUMMARY: PHMSA has determined that the minimum random drug testing... percentage of covered employees for random drug testing. Pursuant to 49 CFR 199.105(c)(2), (3), and (4), the...

  20. 77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2012-01-18

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY... Percentage Rate for Random Drug Testing. SUMMARY: PHMSA has determined that the minimum random drug testing... percentage of covered employees for random drug testing. Pursuant to 49 CFR 199.105(c)(2), (3), and (4), the...

  1. 75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-02-26

    ... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY... Percentage Rate for Random Drug Testing. SUMMARY: PHMSA has determined that the minimum random drug testing... percentage of covered employees for random drug testing. Pursuant to 49 CFR 199.105(c)(2), (3), and (4), the...

  2. 49 CFR 199.107 - Drug testing laboratory.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Drug testing laboratory. 199.107 Section 199.107... § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this part only drug testing laboratories certified by the Department of Health and Human Services under...

  3. 10 CFR 707.10 - Drug testing for reasonable suspicion of illegal drug use.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Drug testing for reasonable suspicion of illegal drug use... Procedures § 707.10 Drug testing for reasonable suspicion of illegal drug use. (a)(1) It may be necessary to... relating to the testing for the use of illegal drugs are not intended to prohibit the contractor from...

  4. Sensitization for Anticancer Drug-Induced Apoptosis by Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2005-02-01

    Full Text Available We previously described that betulinic acid (BetA, a naturally occurring pentacyclic triterpenoid, induces apoptosis in tumor cells through the mitochondrial pathway. Here, for the first time, we provide evidence that BetA cooperated with anticancer drugs to induce apoptosis and to inhibit clonogenic survival of tumor cells. Combined treatment with BetA and anticancer drugs acted in concert to induce loss of mitochondrial membrane potential and the release of cytochrome c and Smac from mitochondria, resulting in activation of caspases and apoptosis. Overexpression of Bcl-2, which blocked mitochondrial perturbations, also inhibited the cooperative effect of BetA and anticancer drugs, indicating that cooperative interaction involved the mitochondrial pathway. Notably, cooperation of BetA and anticancer drugs was found for various cytotoxic compounds with different modes of action (e.g., doxorubicin, cisplatin, Taxol, VP16, or actinomycin D. Importantly, BetA and anticancer drugs cooperated to induce apoptosis in different tumor cell lines, including p53 mutant cells, and also in primary tumor cells, but not in human fibroblasts indicating some tumor specificity. These findings indicate that using BetA as sensitizer in chemotherapy-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy, which warrants further investigation.

  5. [Thyroid function tests in acute drug intoxication].

    Science.gov (United States)

    Tseng, F Y; Chen, C S

    1992-03-01

    It is well known that thyroid function tests may be changed in non-thyroidal illnesses. To understand the influence of acute drug intoxication on thyroid function tests, 31 drug intoxicated patients without previous thyroid disorders and systemic diseases were included in our study. T3, T4, TSH, and resin T3 uptake were checked as soon as they arrived at our emergency service and were compared to that of 58 healthy volunteers. Within 31 patients, 14 were intoxicated by organophosphorous compounds, 6 by sedatives and hypnotics, 3 by strong acid, 2 by paraquet, 2 by rodenticides (warfarin), 2 by lysol and the other 2 were intoxicated by acetaminophen. The mean T3 and TSH levels were significantly lower in the drug intoxicated group. Among the 31 patients, 14 (45.2%) had a low T3, 2 (6.5%) had a low T3 and T4, and 6 (19.3%) had an elevated T4. All of the patients with an elevated T4 were intoxicated by organophosphates. If we divided the 31 patients into 2 subgroups: organophosphate intoxicated group and non-organophosphate intoxicated group, T4 and FT4I were significantly higher in the former group. Thyroid function tests became normal after treatment in 27 patients, discharged in good general condition. T3 and T4 became extremely low in 4 patients before they expired. The present study confirms that acute drug intoxication, like other non-thyroidal illnesses, affects thyroid function tests. Acute organophosphate intoxication may cause transient hyperthyroxinemia.

  6. Does Drug Testing Deter Drug Court Participants from Using Drugs or Alcohol?

    Science.gov (United States)

    Kleinpeter, Christine B.; Brocato, Jo; Koob, Jeffrey J.

    2010-01-01

    This study evaluates 3 drug-testing strategies implemented in 5 different jurisdictions with drug courts in Orange County, California. The purpose of the study was to determine whether the sweat patch acts as a deterrent and under what conditions it can be used to improve outcomes. Results indicated that although the use of the sweat patch did not…

  7. 49 CFR 219.601 - Railroad random drug testing programs.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Railroad random drug testing programs. 219.601... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.601 Railroad random drug testing programs. (a) Submission. Each railroad must submit for FRA...

  8. 76 FR 79204 - Random Drug Testing Rate for Covered Crewmembers

    Science.gov (United States)

    2011-12-21

    ... SECURITY Coast Guard Random Drug Testing Rate for Covered Crewmembers AGENCY: Coast Guard, DHS. ACTION: Notice of minimum random drug testing rate. SUMMARY: The Coast Guard has set the calendar year 2012 minimum random drug testing rate at 50 percent of covered crewmembers. DATES: The minimum random drug...

  9. 49 CFR 219.603 - Participation in drug testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Participation in drug testing. 219.603 Section 219... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.603 Participation in drug testing. A railroad shall, under the conditions specified in this...

  10. 76 FR 1448 - Random Drug Testing Rate for Covered Crewmembers

    Science.gov (United States)

    2011-01-10

    ... SECURITY Coast Guard Random Drug Testing Rate for Covered Crewmembers AGENCY: Coast Guard, DHS. ACTION: Notice of minimum random drug testing rate. SUMMARY: The Coast Guard has set the calendar year 2011 minimum random drug testing rate at 50 percent of covered crewmembers. DATES: The minimum random drug...

  11. 49 CFR 219.605 - Positive drug test results; procedures.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2010-10-01 2010-10-01 false Positive drug test results; procedures. 219.605...

  12. 10 CFR 707.8 - Applicant drug testing.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy... testing. An applicant for a testing designated position will be tested for the use of illegal drugs before... contractors from conducting drug testing on applicants for employment in any position. ...

  13. Glutamate-gated chloride channels of Haemonchus contortus restore drug sensitivity to ivermectin resistant Caenorhabditis elegans.

    Science.gov (United States)

    Glendinning, Susan K; Buckingham, Steven D; Sattelle, David B; Wonnacott, Susan; Wolstenholme, Adrian J

    2011-01-01

    Anthelmintic resistance is a major problem in livestock farming, especially of small ruminants, but our understanding of it has been limited by the difficulty in carrying out functional genetic studies on parasitic nematodes. An important nematode infecting sheep and goats is Haemonchus contortus; in many parts of the world this species is resistant to almost all the currently available drugs, including ivermectin. It is extremely polymorphic and to date it has proved impossible to relate any sequence polymorphisms to its ivermectin resistance status. Expression of candidate drug-resistance genes in Caenorhabditis elegans could provide a convenient means to study the effects of polymorphisms found in resistant parasites, but may be complicated by differences between the gene families of target and model organisms. We tested this using the glutamate-gated chloride channel (GluCl) gene family, which forms the ivermectin drug target and are candidate resistance genes. We expressed GluCl subunits from C. elegans and H. contortus in a highly resistant triple mutant C. elegans strain (DA1316) under the control of the avr-14 promoter; expression of GFP behind this promoter recapitulated the pattern previously reported for avr-14. Expression of ivermectin-sensitive subunits from both species restored drug sensitivity to transgenic worms, though some quantitative differences were noted between lines. Expression of an ivermectin-insensitive subunit, Hco-GLC-2, had no effect on drug sensitivity. Expression of a previously uncharacterised parasite-specific subunit, Hco-GLC-6, caused the transgenic worms to become ivermectin sensitive, suggesting that this subunit also encodes a GluCl that responds to the drug. These results demonstrate that both orthologous and paralogous subunits from C. elegans and H. contortus are able to rescue the ivermectin sensitivity of mutant C. elegans, though some quantitative differences were observed between transgenic lines in some assays. C

  14. Glutamate-gated chloride channels of Haemonchus contortus restore drug sensitivity to ivermectin resistant Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Susan K Glendinning

    Full Text Available Anthelmintic resistance is a major problem in livestock farming, especially of small ruminants, but our understanding of it has been limited by the difficulty in carrying out functional genetic studies on parasitic nematodes. An important nematode infecting sheep and goats is Haemonchus contortus; in many parts of the world this species is resistant to almost all the currently available drugs, including ivermectin. It is extremely polymorphic and to date it has proved impossible to relate any sequence polymorphisms to its ivermectin resistance status. Expression of candidate drug-resistance genes in Caenorhabditis elegans could provide a convenient means to study the effects of polymorphisms found in resistant parasites, but may be complicated by differences between the gene families of target and model organisms. We tested this using the glutamate-gated chloride channel (GluCl gene family, which forms the ivermectin drug target and are candidate resistance genes. We expressed GluCl subunits from C. elegans and H. contortus in a highly resistant triple mutant C. elegans strain (DA1316 under the control of the avr-14 promoter; expression of GFP behind this promoter recapitulated the pattern previously reported for avr-14. Expression of ivermectin-sensitive subunits from both species restored drug sensitivity to transgenic worms, though some quantitative differences were noted between lines. Expression of an ivermectin-insensitive subunit, Hco-GLC-2, had no effect on drug sensitivity. Expression of a previously uncharacterised parasite-specific subunit, Hco-GLC-6, caused the transgenic worms to become ivermectin sensitive, suggesting that this subunit also encodes a GluCl that responds to the drug. These results demonstrate that both orthologous and paralogous subunits from C. elegans and H. contortus are able to rescue the ivermectin sensitivity of mutant C. elegans, though some quantitative differences were observed between transgenic lines in

  15. Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery.

    Science.gov (United States)

    Alvarez-Lorenzo, Carmen; Blanco-Fernandez, Barbara; Puga, Ana M; Concheiro, Angel

    2013-08-01

    Polysaccharides are gaining increasing attention as components of stimuli-responsive drug delivery systems, particularly since they can be obtained in a well characterized and reproducible way from the natural sources. Ionic polysaccharides can be readily crosslinked to render hydrogel networks sensitive to a variety of internal and external variables, and thus suitable for switching drug release on-off through diverse mechanisms. Hybrids, composites and grafted polymers can reinforce the responsiveness and widen the range of stimuli to which polysaccharide-based systems can respond. This review analyzes the state of the art of crosslinked ionic polysaccharides as components of delivery systems that can regulate drug release as a function of changes in pH, ion nature and concentration, electric and magnetic field intensity, light wavelength, temperature, redox potential, and certain molecules (enzymes, illness markers, and so on). Examples of specific applications are provided. The information compiled demonstrates that crosslinked networks of ionic polysaccharides are suitable building blocks for developing advanced externally activated and feed-back modulated drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Direct Sensitivity Test of the MB/BacT System

    Directory of Open Access Journals (Sweden)

    Barreto Angela Maria Werneck

    2002-01-01

    Full Text Available In order to evaluate the direct-method test of sensitivity to drugs used in the principal tuberculosis treatment regimes, in the Organon Teknika MB/BacT system, we tested 50 sputum samples positive to microscopy taken from patients with pulmonary tuberculosis and with clinical indications for an antibiogram, admitted sequentially for examination during the routine of the reference laboratory. The material was treated v/v with 23% trisodium phosphate solution, incubated for 24 h at 35°C, and neutralized v/v with 20% monosodium phosphate solution. The material was then centrifuged and the sediment inoculated into flasks containing Rifampin - 2 µg/ml, Isoniazid - 0.2 µg/ml, Pyrazinamide - 100 µg/ml, Ethambutol - 2.5 µg/ml, Ethionamide - 1.25 µg/ml, and Streptomycin - 2 µg/ml. The tests were evaluated using the indirect method in the BACTEC 460 TB (Becton Dickinson system as the gold standard. The results showed that the Rifampin test performed best, i.e., 100% sensitivity at 95% Confidence Interval (82.2-100 and 100% specificity at 95% Confidence Interval (84.5-100, followed by Isoniazid and Pyrazinamide. In this experiment, 92% of the materials showed a final reading in 30 days; this period represents the time for primary isolation as well as the results of the sensitivity profile, and is within Centers for Disease Control and Prevention recommendations regarding time for performance of the antibiogram. The inoculated flasks showed no contamination during the experiment. The MB/BacT is shown to be a reliable, rapid, fully automated nonradiometric system for the tuberculosis antibiogram.

  17. Distribution and drug sensitivity of pathogens in diabetic foot ulcer secretions

    Institute of Scientific and Technical Information of China (English)

    李惠琴

    2013-01-01

    Objective To investigate the distribution and drug sensitivity of pathogens isolated from diabetic foot ulcer(DFU) secretions. Methods A retrospective study was carried out on the distribution and drug sensitivity of pathogens isolated from the secretions of 218 DFU

  18. Drug susceptibility testing of Mycobacterium Avium subsp. Avium isolates from naturally infected domestic pigeons to avian tuberculosis

    Directory of Open Access Journals (Sweden)

    Kaveh Parvandar

    2016-01-01

    Conclusion: We suggest drug susceptibility testing for more nontuberculous mycobateria, particularly M. avium complex isolated from infected birds and humans, as well as molecular basics of drug sensitivity in order to detect resistance genes of pathogenic M. avium subsp. avium.

  19. Performance of newer and conventional diagnostic methods in detection of drug sensitive and resistant tuberculous meningitis

    Directory of Open Access Journals (Sweden)

    Sangamithra Neelakantan

    2014-09-01

    Full Text Available Objective: To compare the performance of traditional and newer diagnostic methods for diagnosis of tuberculous meningitis (TBM along with detection of drug resistant TBM. Methods: Single cerebrospinal fluids sample from 281 suspected TBM patients was processed during August 2011 to July 2012 for acid fast bacilli (AFB examination by Ziehl-Neelsen and auramine staining methods, AFB culture on Lowenstein-Jensen culture media, by microscope observation of drug susceptibility testing assay, and nucleic acid amplification tests by inhouse conventional PCR and in-house real time PCR targeting IS6110 insertion sequence. All the isolates were subjected to drug susceptibility testing for isoniazid, rifampicin, ethambutol and streptomycin by 1% proportion method. Results: The percentage positivity by AFB smear examination and culture on Lowenstein-Jensen media was 21% (59/281, 11.4% (32/281 respectively. The detection rate by conventional PCR was 33.1% (93/281. The real time PCR showed positivity rate of 44.8% (126/281. The extra detection by real time PCR was 11.7%. Only one isolate was multiple drug resistant and 22 (68.8% were pan-susceptible. Remaining eight isolates showed either mono/poly drug resistant to first line antitubercular drugs. Conclusions: Real time PCR is a more sensitive and rapid method if it is appropriately adopted in clinical practice for diagnosis of TBM. Prevalence of multiple drug resistance Mycobacterium tuberculosis causing TBM is low.

  20. Preparation and characterization of PEG-modified polyurethane pressure-sensitive adhesives for transdermal drug delivery.

    Science.gov (United States)

    Chen, Xuemei; Liu, Wei; Zhao, Yanbing; Jiang, Lingyu; Xu, Huibi; Yang, Xiangliang

    2009-06-01

    The purpose of this work was to develop novel pressure-sensitive adhesives (PSAs) for transdermal drug-delivery systems (TDDS) with proper adhesive properties, hydrophilicity, biocompatibility and high drug loading. Polyethyleneglycol-modified polyurethane PSAs (PEG-PU-PSAs) were synthesized by prepolymerization method with PEG-modified co-polyether and hexamethylene diisocyanate. The effects of reaction temperature, catalyst, ratios of NCO/OH, co-polyether composition, and chain extender were investigated. Drug loading was studied by using thiamazole (hydrophilic drug), diclofenac sodium (slightly hydrophilic drug), and ibuprofen (lipophilic drug) as model drugs. In vitro drug-release kinetics obtained with Franz diffusion cell and dialysis membrane. The results showed that when reaction temperature at 80 degrees C, weight percentage of stannous octoate as catalyst at 0.05%, ratio of NCO/OH at 2.0-2.2, ratio of PEG/polypropylene glycol (PPG)/polytetramethylene ether glycol (PTMG) at 30/25-30/50-55, and weight percentage of glycol as chain extender at 4.5%, PEGPU-PSAs synthesized performed well on adhesive properties. Actually, PEG on the main chain of the PU could improve the hydrophilicity of PSAs, whereas PPG and PTMG could offer proper adhesive properties. Skin compatibility test on volunteers indicated that PEG-PU-PSAs would not cause any skin irritations. All the model drugs had excellent stabilizations in PEG-PU-PSAs. In vitro drug-release kinetics demonstrated that the drug release depended on drug-loading level and solubility of the drug. These experimental results indicated that PEG-PU-PSAs have good potential for applications in TDDS.

  1. Lamb waves increase sensitivity in nondestructive testing

    Science.gov (United States)

    Di Novi, R.

    1967-01-01

    Lamb waves improve sensitivity and resolution in the detection of small defects in thin plates and small diameter, thin-walled tubing. This improvement over shear waves applies to both longitudinal and transverse flaws in the specimens.

  2. Comparison of Urine and Oral Fluid for Workplace Drug Testing.

    Science.gov (United States)

    Casolin, Armand

    2016-09-01

    To determine the relative detection rates of urine versus oral fluid testing in a safety sensitive industry and the correlation with diagnosed substance use disorders and possible impairment at work. The trial involved 1,500 paired urine and oral fluid tests performed in accordance with Australian Standard/New Zealand Standard (AS/NZS) 4308:2008 and AS 4760:2006. Workers who returned a positive test were screened for substance use disorders, as defined by DSM-5, and for possible impairment at work following that particular episode of substance use. Substances were detected in 3.7% (n = 56) of urine samples and 0.5% (n = 8) of oral fluid samples (p drug or a controlled substance without a clinical indication and prescription. Nine workers tested positive on urine alone, one on oral fluid alone and two on both (p = 0.0114). Of note, 6/11 workers who tested positive on urine had possible impairment at work and 2/11 had a substance use disorder versus 2/3 and 0/3, respectively, who tested positive on oral fluid. Urine drug testing performed in accordance with AS/NZS 4308:2008 is more likely to detect overall substance use and illicit drug use than oral fluid testing conducted in accordance with AS 4760:2006. Urine testing performed in accordance with AS/NZS 4308:2008 may also be more likely to detect workers with possible impairment at work and substance use disorders than oral fluid testing performed in accordance with AS 4760:2006. © The Author 2016. Published by Oxford University Press.

  3. Medication monitoring and drug testing ethics project.

    Science.gov (United States)

    Payne, Richard; Moe, Jeffrey L; Sevier, Catherine Harvey; Sevier, David; Waitzkin, Michael

    2015-01-01

    In 2012, Duke University initiated a research project, funded by an unrestricted research grant from Millennium Laboratories, a drug testing company. The project focused on assessing the frequency and nature of questionable, unethical, and illegal business practices in the clinical drug testing industry and assessing the potential for establishing a business code of ethics. Laboratory leaders, clinicians, industry attorneys, ethicists, and consultants participated in the survey, were interviewed, and attended two face-to-face meetings to discuss a way forward. The study demonstrated broad acknowledgment of variations in the legal and regulatory environment, resulting in inconsistent enforcement of industry practices. Study participants expressed agreement that overtly illegal practices sometimes exist, particularly when laboratory representatives and clinicians discuss reimbursement, extent of testing, and potential business incentives with medical practitioners. Most respondents reported directly observing probable violations involving marketing materials, contracts, or, in the case of some individuals, directly soliciting people with offers of clinical supplies and other "freebies." While many study respondents were skeptical that voluntary standards alone would eliminate questionable business practices, most viewed ethics codes and credentialing as an important first step that could potentially mitigate uneven enforcement, while improving quality of care and facilitating preferred payment options for credentialed parties. Many were willing to participate in future discussions and industry-wide initiatives to improve the environment.

  4. Retrospective evaluation of the consequence of alleged patch test sensitization

    DEFF Research Database (Denmark)

    Jensen, Charlotte D; Paulsen, Evy; Andersen, Klaus E

    2006-01-01

    consequences in cases of possible patch test sensitization. Among 7619 consecutively tested eczema patients in a 14-year period 26 (0.3%) were identified in the database as having had a late patch test reaction, which may be an indication of patch test sensitization. 9 of these cases were not suitable....... For the remaining 11 patients we could not rule out that they were patch test sensitized, and they were investigated further. 1 was diseased and 10 were interviewed regarding the possible consequences of the alleged patch test sensitization. 9 had not experienced any dermatitis problems, and 1 could not exclude...

  5. Analytical evaluation of four on-site oral fluid drug testing devices.

    Science.gov (United States)

    Vanstechelman, Sylvie; Isalberti, Cristina; Van der Linden, Trudy; Pil, Kristof; Legrand, Sara-Ann; Verstraete, Alain G

    2012-03-01

    The use of oral fluid (OF) as an alternative matrix for the detection of drugs of abuse has increased over the last decade, leading to the need for a rapid, simple, and reliable on-site OF testing device. Four on-site OF drug testing devices (Dräger DrugTest 5000, Cozart DDS, Mavand Rapid STAT, and Innovacon OrAlert) were evaluated on 408 volunteers at drug treatment centers. UPLC-MS-MS results were used as reference to determine sensitivity, specificity and accuracy for each device, applying Belgian legal confirmation cutoffs for benzoylecgonine, cocaine, and THC (10 ng/mL); morphine and 6-acetylmorphine (5 ng/mL); and amphetamine and 3,4-methylenedioxymethylamphetamine (25 ng/mL). Sensitivity for cocaine was 50%, 50%, 27%, and 11% for DrugTest, OrAlert, Rapid STAT, and DDS 806, respectively. For opiates, sensitivities were 84%, 73%, 77%, and 65%, respectively. For THC, the sensitivities were 81%, 23%, 43%, and 28%, respectively. For amphetamines, the sensitivities were 75%, 33%, 17%, and 67%, respectively. Specificity was >88% for opiates and THC, > 90% for amphetamines, and > 97% for cocaine. All tests showed good specificity. DrugTest had the highest sensitivity, although it was still low for some analytes.

  6. Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence

    NARCIS (Netherlands)

    Waard, de M.A.; Andrade, A.C.; Hayashi, K.; Schoonbeek, H.; Stergiopoulos, I.; Zwiers, L.H.

    2006-01-01

    Drug transporters are membrane proteins that provide protection for organisms against natural toxic products and fungicides. In plant pathogens, drug transporters function in baseline sensitivity to fungicides, multidrug resistance (MDR) and virulence on host plants. This paper describes drug transp

  7. The Relationship between Student Illicit Drug Use and School Drug-Testing Policies.

    Science.gov (United States)

    Yamaguchi, Ryoko; Johnston, Lloyd D.; O'Malley, Patrick M.

    This report provides information about drug testing by American secondary schools, based on results from national surveys. The purposes of this study are (1) to provide descriptive information on drug testing practices by schools from 1998 to 2001, and (2) to examine the association between drug testing by schools and reported drug use by…

  8. Drug Testing and Searches in Public Schools: A Legal Analysis.

    Science.gov (United States)

    Minnesota House of Representatives, St. Paul. Research Dept.

    This document examines the Fourth Amendment as the source of search and seizure law; drug testing of school employees; and drug testing searches of students. The United States Supreme Court case that established the two-part test to determine the legality of a student search is discussed, three separate student drug testing programs that have been…

  9. [Interventional neuroradiology. Drug treatment, monitoring and function tests].

    Science.gov (United States)

    Laurent, A; Gobin, Y P; Launay, F; Aymard, A; Casasco, A; Merland, J J

    1994-04-23

    Specialized monitoring as well as function tests and drug therapy play an ever growing role in neuroradiological procedures. The particular route of administration and the territories involved in neuroradiology require special precautions. Anaesthesia must enable the operators to monitor the central nervous system since the patients must remain totally immobilized for several hours. Catheterization is made safe by careful asepsia and antibiotic prophylaxis and by preventing embolic events, particularly in neuro-cervico-facial interventions where an anticoagulant protocol is important. Arterial spasms can be prevented or cured with calcium inhibitors. The safety of the procedure itself is guaranteed by various function tests including sensitivity to ischaemia using anaesthetic barbiturates, controlled clampings or the lidocaine test. Undesirable effects of both emboli (e.g. toxicity of cyanoacrylate glue) and embolization (e.g. subsequent venous thrombosis) can be prevented by adapted anti-inflammatory drugs. Herein, we describe the routine monitoring conditions, drugs prescribed and function tests performed at the Therapeutic Angiography Department of the Lariboisière Hospital, Paris.

  10. To Test or Not to Test? Drug Testing Teachers: The View of the Superintendent

    Science.gov (United States)

    DeMitchell, Todd A.; Kossakoski, Stephen; Baldasaro, Tony

    2008-01-01

    Purpose: School superintendents are charged with maintaining the safety and security of the schools in their district. One major recognized threat to the security and safety of students and staff is the use of illegal drugs. Superintendents are responding to the constitutionality of student drug-testing policies by implementing drug-testing…

  11. Successful analysis of anticancer drug sensitivity by CD-DST using pleural fluid and ascites from patients with advanced ovarian cancer: case reports.

    Science.gov (United States)

    Kawaguchi, Makiko; Banno, Kouji; Susumu, Nobuyuki; Yanokura, Megumi; Kuwabara, Yoshiko; Hirao, Nobumaru; Tsukazaki, Katsumi; Nozawa, Shiro

    2005-01-01

    In vitro anticancer drug sensitivity tests have been performed for various types of cancers, and a relationship with clinical response has been observed. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is a new in vitro anticancer drug sensitivity test by Yabushita et al., recently reported to be useful in ovarian cancer. CD-DST allows analysis of a small number of cells, compared to other anticancer drug sensitivity tests. Here, we report a successful analysis of anticancer drug sensitivity by CD-DST using cancerous ascites and pleural fluid samples from 2 patients with advanced ovarian cancer. To our knowledge, this is only the second report of the application of CD-DST in ovarian cancer, and our results suggest that CD-DST could be helpful in the selection of anticancer drugs for neoadjuvant chemotherapy in advanced ovarian cancer.

  12. Photoactive Fluoropolymer Surfaces that Release Sensitizer Drug Molecules

    Science.gov (United States)

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A.; Abramova, Inna; Cengel, Keith; Busch, Theresa M.; Greer, Alexander

    2015-01-01

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer which generates 1O2(1Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/polyvinylalcohol (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, 1O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68–92% yields. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only high O2 solubility and drug repellency, but that the C−F bonds physically quench little 1O2 for its productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses of delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT). PMID:25686407

  13. Photoactive fluoropolymer surfaces that release sensitizer drug molecules.

    Science.gov (United States)

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A; Abramova, Inna; Cengel, Keith A; Busch, Theresa M; Greer, Alexander

    2015-03-12

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer that generates (1)O2((1)Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/poly(vinyl alcohol) (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al. J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, (1)O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68-92% yield. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only on high O2 solubility and drug repellency but also on the C-F bonds, which physically quench little (1)O2, for singlet oxygen's productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses in delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT).

  14. A Simple in-vitro Test for Assessing the Sensitivity of Lymphocytes to Chlorambucil

    Science.gov (United States)

    Lawler, Sylvia D.; Lele, Kusum P.; Pentycross, C. R.

    1971-01-01

    The sensitivity of lymphocytes to chlorambucil has been assessed by a simple in-vitro test which has been applied to the cells of normal controls and of patients with chronic lymphocytic leukaemia. The degree of sensitivity varied amongst the normal controls and in-vitro resistance of the lymphocytes in the patients was sometimes found in the absence of in-vivo experience of the drug. Resistance in-vitro tended to be associated with very high total peripheral blood lymphocyte counts but not with the age of the patient. Where the information was available the in-vitro sensitivity test agreed with the results of biochemical estimations of drug resistance and with the clinical responses to the drug. It is suggested that this test may have applications in patient management. PMID:5144524

  15. 78 FR 4855 - Random Drug Testing Rate for Covered Crewmembers

    Science.gov (United States)

    2013-01-23

    ... SECURITY Coast Guard Random Drug Testing Rate for Covered Crewmembers AGENCY: Coast Guard, DHS. ACTION: Notice of minimum random drug testing rate. SUMMARY: The Coast Guard has set the calendar year 2013 minimum random drug testing rate at 25 percent of covered crewmembers. The Coast Guard will continue to...

  16. 49 CFR 219.501 - Pre-employment drug testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Pre-employment drug testing. 219.501 Section 219...-employment drug testing. (a) Prior to the first time a covered employee performs covered service for a railroad, the employee must undergo testing for drugs. No railroad may allow a covered employee to perform...

  17. Proposed Policy: Drug Testing of Hawaii's Public School Teachers

    Science.gov (United States)

    Davis, Bebi

    2007-01-01

    Because of a proposed policy, public school teachers in Hawaii are facing the possibility of being randomly tested for illegal drugs. Random drug testing has many implications and its impact is questionable. In this article, the author scrutinizes the controversial drug-testing policy for both troubling and promising aspects and how educators may…

  18. 21 CFR 343.90 - Dissolution and drug release testing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Dissolution and drug release testing. 343.90...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) [Reserved] (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in...

  19. 78 FR 37231 - Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-06-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry; Guidance on Abbreviated New Drug... the availability of a guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and... generic drug review, FDA is recommending that the generic drug industry follow the approach in...

  20. 77 FR 58999 - Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2012-09-25

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug... availability of a draft guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and... of a draft guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and...

  1. Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Nisana Tepsiri; Liengchai Chaturat; Banchob Sripa; Wises Namwat; Sopit Wongkham; Vajarabhongsa Bhudhisawasdi; Wichittra Tassaneeyakul

    2005-01-01

    AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase P1 (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined.METHODS: Five human CCA cell lines (KKU-100, KKU M055, KKU-M156, KKU-M214 and KKU-OCA17) weretreated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC50 values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC50 values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC50 values (<5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC50 values of etoposide, doxorubicin and pirarubicin (r = 0.86-0.98, ,P<0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug

  2. Identification and Drug Sensitivity Test of Salmonella choleraesuis Isolated from the Scale Pig Farm%规模化猪场猪霍乱沙门氏菌的分离鉴定与药敏试验

    Institute of Scientific and Technical Information of China (English)

    刘俊伟; 张海棠; 张志鹏; 赵彩丽; 申红艳; 王自良

    2011-01-01

    Some organic and tissue samples of the diseased pigs of suspected swine salmonellosis were collected from a scale ig farm in Xinxiang city. Bacterial isolating culture,biochemical identification,animal experiments and drug sensitivity were performed. The results showed that one small Gram-negative bacillus which represented the needle-shape, clour-less transparent, smooth and circular on the Macconkey medium was isolated. Positive reactions to glucose, xylitol, lysine, mannitol, sugar, fruit sugar and sorbitol rather than mannose, hyduogen sulphide, phenyla lanine, urease were observed. The bacillus can cause death in little white mouse. This indicates that the bacteria presently isolated were Salmonella choleraesuis. The bacterium was sensitive to ceftiofur sodium and levofloxacin, intermediate to norfloxacin and neomycin, but resistant to florfenicol, ampicillin and gentamicin. The data provided some theoretic guidance for the prevention and treatment of swine salmonellsis.%采集新乡市某规模化猪场疑似猪沙门氏菌病的病料,通过细菌分离培养、生化鉴定、动物试验和药敏试验,分离到1株革兰氏阴性小杆菌,该菌在麦康凯琼脂平板上呈细小、无色半透明、光滑、圆整的菌落,对葡萄糖、木糖醇、赖氨酸、甘露醇、蔗糖、果糖和山梨醇反应阳性,对甘露糖、硫化氢、苯丙氨酸、尿素酶反应呈阴性,可致死小白鼠,确定所分离的细菌为猪霍乱沙门氏菌.该菌对头孢噻呋、左旋氧氟沙星等敏感,对诺氟沙星和新霉素中介,对氟苯尼考、氨苄西林、庆大霉素等耐药.该研究为猪沙门氏菌病的防治提供理论依据.

  3. Molecular characterization of drug-resistant and drug-sensitive Aspergillus isolates causing infectious keratitis

    Directory of Open Access Journals (Sweden)

    Niranjan Nayak

    2011-01-01

    Full Text Available Purpose: To study the susceptibilities of Aspergillus species against amphotericin B in infectious keratitis and to find out if drug resistance had any association with the molecular characteristics of the fungi. Materials and Methods: One hundred and sixty Aspergillus isolates from the corneal scrapings of patients with keratitis were tested for susceptibilities to amphotericin B by broth microdilution method. These included Aspergillus flavus (64 isolates, A. fumigatus (43 and A. niger (53. Fungal DNA was extracted by glass bead vertexing technique. Polymerase chain reaction (PCR assay was standardized and used to amplify the 28S rRNA gene. Single-stranded conformational polymorphism (SSCP of the PCR product was performed by the standard protocol. Results: Of the 160 isolates, 84 (52.5% showed low minimum inhibitory concentration (MIC values (≤ 1.56 μg/ml and were designated as amphotercin B-sensitive. Similarly, 76 (47.5% had high MICs (≥ 3.12 μg/ml and were categorized as amphotericin B-resistant. MIC 50 and MIC 90 values ranged between 3.12-6.25 μg/ml and 3.12-12.5 μg/ml respectively. A. flavus and A. niger showed higher MIC 50 and MIC 90 values than A. fumigatus. The SSCP pattern exhibited three extra bands (150 bp, 200 bp and 250 bp each in addition to the 260 bp amplicon. Strains (lanes 1 and 7 lacking the 150 bp band showed low MIC values (≤ 1.56 μg/ml. Conclusion: A. niger and A. flavus isolates had higher MICs compared to A. fumigatus, suggesting a high index of suspicion for amphotericin B resistance. PCR-SSCP was a good molecular tool to characterize Aspergillus phenotypes in fungal keratitis.

  4. A pH-Sensitive Injectable Nanoparticle Composite Hydrogel for Anticancer Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yuanfeng Ye

    2016-01-01

    Full Text Available According to previous reports, low pH-triggered nanoparticles were considered to be excellent carriers for anticancer drug delivery, for the reason that they could trigger encapsulated drug release at mild acid environment of tumor. Herein, an acid-sensitive β-cyclodextrin derivative, namely, acetalated-β-cyclodextrin (Ac-β-CD, was synthesized by acetonation and fabricated to nanoparticles through single oil-in-water (o/w emulsion technique. At the same time, camptothecin (CPT, a hydrophobic anticancer drug, was encapsulated into Ac-β-CD nanoparticles in the process of nanoparticle fabrication. Formed nanoparticles exhibited nearly spherical structure with diameter of 209±40 nm. The drug release behavior of nanoparticles displayed pH dependent changes due to hydrolysis of Ac-β-CD. In order to overcome the disadvantages of nanoparticle and broaden its application, injectable hydrogels with Ac-β-CD nanoparticles were designed and prepared by simple mixture of nanoparticles solution and graphene oxide (GO solution in this work. The injectable property was confirmed by short gelation time and good mobility of two precursors. Hydrogels were characterized by dynamic mechanical test and SEM, which also reflected some structural features. Moreover, all hydrogels underwent a reversible sol-gel transition in alkaline environment. Finally, the results of in vitro drug release profile indicated that hydrogel could control drug release or bind drug inside depending on the pH value of released medium.

  5. Aspergillus nidulans galactofuranose biosynthesis affects antifungal drug sensitivity.

    Science.gov (United States)

    Alam, Md Kausar; El-Ganiny, Amira M; Afroz, Sharmin; Sanders, David A R; Liu, Juxin; Kaminskyj, Susan G W

    2012-12-01

    The cell wall is essential for fungal survival in natural environments. Many fungal wall carbohydrates are absent from humans, so they are a promising source of antifungal drug targets. Galactofuranose (Galf) is a sugar that decorates certain carbohydrates and lipids. It comprises about 5% of the Aspergillus fumigatus cell wall, and may play a role in systemic aspergillosis. We are studying Aspergillus wall formation in the tractable model system, A. nidulans. Previously we showed single-gene deletions of three sequential A. nidulans Galf biosynthesis proteins each caused similar hyphal morphogenesis defects and 500-fold reduced colony growth and sporulation. Here, we generated ugeA, ugmA and ugtA strains controlled by the alcA(p) or niiA(p) regulatable promoters. For repression and expression, alcA(p)-regulated strains were grown on complete medium with glucose or threonine, whereas niiA(p)-regulated strains were grown on minimal medium with ammonium or nitrate. Expression was assessed by qPCR and colony phenotype. The alcA(p) and niiA(p) strains produced similar effects: colonies resembling wild type for gene expression, and resembling deletion strains for gene repression. Galf immunolocalization using the L10 monoclonal antibody showed that ugmA deletion and repression phenotypes correlated with loss of hyphal wall Galf. None of the gene manipulations affected itraconazole sensitivity, as expected. Deletion of any of ugmA, ugeA, ugtA, their repression by alcA(p) or niiA(p), OR, ugmA overexpression by alcA(p), increased sensitivity to Caspofungin. Strains with alcA(p)-mediated overexpression of ugeA and ugtA had lower caspofungin sensitivity. Galf appears to play an important role in A. nidulans growth and vigor.

  6. Sensitivity of solid rocket propellants for card gap test

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Eishu; Oyumi, Yoshio (Japan Defense Agency, Tokyo (Japan). Technical Research and Development Inst.)

    1999-05-01

    Card gap test, which is standardized in Japan Explosives Society, was modified in order to apply it to solid rocket propellants and carried out to evaluate sensitivities against shock stimuli. Solid propellants tested here were mainly azide polymer composite propellants, which contained ammonium nitrate (AN) as a main oxidizer. Double base propellant, composed nitroglycerin and nitrocellulose (NC), and ammonium perchlorate (AP)-based composite propellants. It is found that the sensitivity was dominated by the oxidizer characteristics. AP- and AN-based propellant had less sensitivity and HMX-based propellant showed higher sensitivity, and the adding of NC and TMETN contributed to worse sensitive for the card gap test. Good relationship was obtained between the card gap sensitivity and the oxygen balance of propellants tested here. (orig.)

  7. What You Need To Know about Drug Testing in Schools.

    Science.gov (United States)

    Office of National Drug Control Policy, Washington, DC.

    The Office of National Drug Control policy has put together this guide to assist educators, parents, and community leaders in determining whether student drug testing is appropriate for their schools. The aim is to provide anyone considering a drug-testing program in his or her community with a broad understanding of the issue and solid,…

  8. 14 CFR 120.35 - Testing for prohibited drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Testing for prohibited drugs. 120.35... (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS DRUG AND... for prohibited drugs. (a) Each certificate holder or operator shall test each of its employees...

  9. 75 FR 1547 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2010

    Science.gov (United States)

    2010-01-12

    ... Federal Railroad Administration 49 CFR Part 219 RIN 2130-AA81 Alcohol and Drug Testing: Determination of... percent for drugs and 0.15 percent for alcohol. Because the industry-wide random drug testing positive... (Administrator) has determined that the minimum annual random drug testing rate for the period January 1, 2010...

  10. Isolation,Identification and Drug Sensitivity Test of Clostridium perfringens from Broiler Chickens%鸡产气荚膜梭菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    艾地云; 温国元; 邵华斌; 张腾飞; 詹丽超; 罗玲; 张蓉蓉; 汪宏才; 王红琳; 罗青平

    2014-01-01

    For investigating the prevalence and genetypes of C.perfringens in healthy chickens in Hubei province,120 anus cotton swab samples were collected from large-scale broiler chicken farms in Hubei. After culturing in anaerobic meat liver soup and CW agar culture-medium,9 suspected C.perfringens were isolated and then identified with purple milk test,Gram stain test and biochemical test.The isolation rate was 7.5 %.9 strains were genotyped as type A by PCR.These strains were tested for susceptibility to common antimicrobials.All of the isolates were resistant to streptomycin,neomycin,ciprofloracin,cip-rofloxacin,and were sensitive to ampicillin,amoxicillin,cefotaxime,tetracycline,amikacin and clindamy-cin.%为调查湖北地区健康鸡群中产气荚膜梭菌的分布状况,从规模化养鸡场采集鸡肛门棉拭子样品,应用厌气肉肝汤和 CW 琼脂培养基培养、紫牛乳反应、革兰染色及生化试验进行细菌的分离鉴定,应用多重 PCR 方法对分离菌株进行基因分型,并对分离菌株进行体外药敏试验。结果从120份样品中分离到9株(7.5%)产气荚膜梭菌,多重 PCR 都只扩增出α条带,毒素基因分型结果均为 A 型。药敏试验结果显示,分离菌株对链霉素、新霉素、丙氟哌酸、环丙沙星耐药,对丁胺卡那霉素,氯洁霉素中度敏感,对氨苄西林、阿莫西林、四环素、头孢噻肟高度敏感。

  11. Drug Sensitivity Tests of Pathogenic Bacteria of Dairy Cow Endometritis in Yanmenguan Area of Shanxi Province%山西省雁门关地区奶牛子宫内膜炎致病菌药敏试验

    Institute of Scientific and Technical Information of China (English)

    戴浩楠; 石慧; 郑明学; 王仲兵; 马海利; 韩克光; 古少鹏; 白瑞

    2015-01-01

    In order to provide basis for scientifically preventing and treating cow endometritis in dairy cow farms in Yanmenguan area of Shanxi province.The sensitivity tests of antimicrobials and disinfectants to main pathogenic bacteria causing cow endometritis were conducted.The result showed that above 90% of main pathogenic bacteria were sensitive to florfenicol and levofloxacin;80%-90% of main pathogenic bacteria were sensitive to enrofloxacin and ciprofloxacin;70%-80% of main pathogenic bacteria were sensitive to polymyxin B,ceftiofur,gentamicin and amoxicillin etc;The lincomycin,sulfamonomethoxin and sulfamethoxazole resistances were below 60% of main pathogenic bacteria.It was effective to kill above 90% of pathogenic bacteria for peracetic acid,benzalkonium bro-mide,potassium permanganate,peracetic acid glutaraldehyde compound disinfectants and glutaraldehyde etc.100%of main pathogenic bacteria(propagules and spores)were resistant to povidone iodine.100% of main pathogenic bacterial spores and 43.28% main pathogenic bacterial propagules were resistans to bestaquam-s.In conclusion,it will treat cow endometritis effectively in the area by using florfenicol,levofloxacin,enrofloxacin and so on.It will kill pathogenic bacteria in the environment by using peracetic acid,potassium permanganate and benzalkonium bro-mide etc.in the area,so it can prevent cow endometritis in the area.%为给山西省雁门关地区舍饲养殖场奶牛子宫内膜炎的科学防治提供依据,对该地区引起奶牛子宫内膜炎的主要致病菌进行药物及消毒剂的敏感性试验。结果发现,90%以上的主要致病菌株对氟苯尼考、左氧氟沙星敏感;80%~90%的致病菌株对恩诺沙星、环丙沙星敏感;70%~80%致病菌株对多黏菌素 B、头孢噻呋、庆大霉素、阿莫西林等敏感;小于60%的菌株对林可霉素、磺胺六甲氧、复方新诺明耐药;过氧乙酸、新洁尔灭、高锰酸钾、过氧乙酸戊二醛

  12. European guidelines for workplace drug and alcohol testing in hair.

    Science.gov (United States)

    Salomone, A; Tsanaclis, L; Agius, R; Kintz, P; Baumgartner, M R

    2016-10-01

    Guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). They are based on the 2010 version published by Pascal Kintz and Ronald Agius (Guidelines for European workplace drug and alcohol testing in hair. Drug Test. Anal. 2010, 2, 367) and in concordance with the Society of Hair Testing guidelines (Society of Hair Testing guidelines for drug testing in hair. Forensic Sci. Int. 2012, 218, 20-24). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing use these guidelines as a template for accreditation. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Scientific issues in drug testing: council on scientific affairs

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Isolation and Identification of Pathogenic Bacteria of Gill Rot Disease from Andrias davidianus and Drug Sensitivity Test%大鲵烂鳃病病原菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    贺胜英; 叶华; 游玲

    2014-01-01

    为了确定导致大鲵(Andrias davidianus )烂鳃病的主要病原菌类型,从而为大鲵烂鳃病的确诊和科学防治提供参考,从细菌性感染病鲵的鳃、肝、肾及血液中分离到两株细菌,经形态结构、生理生化特征鉴定、16S rDNA 基因序列分析鉴定为蜡样芽孢杆菌(Bacillus cereus )和栗褐芽孢杆菌(Bacillus badius )。人工感染试验证实栗褐芽孢杆菌(Bacillus badius )为主要致病菌。两种病原菌对恩诺沙星和环丙沙星比较敏感,可作为首选药物治疗该病。%The morphological structure and physiological and biochemical property of two trains isolated from gill,liver,kidney and blood of A.davidianus infected with gill rot disease were identified to determine main pathogenic bacteria types of A.davidianus gill rot disease and to provide a reference for diagnosis and scientific control of A.davidianus gill rot disease.Two stains were identified as B.cereus and Bacillus badius based on 16S rDNA gene sequencing analysis.The artificial infection test confirms that Bacillus cereus is the dominant pathogenic bacteria.Enrofloxacin and CPFX can be used as first choice drugs to control gill rot disease in artificial breeding of A.davidianus.

  15. Highly sensitive silicon microreactor for catalyst testing

    DEFF Research Database (Denmark)

    Henriksen, Toke Riishøj; Olsen, Jakob Lind; Vesborg, Peter Christian Kjærgaard;

    2009-01-01

    by directing the entire gas flow through the catalyst bed to a mass spectrometer, thus ensuring that nearly all reaction products are present in the analyzed gas flow. Although the device can be employed for testing a wide range of catalysts, the primary aim of the design is to allow characterization of model...... catalysts which can only be obtained in small quantities. Such measurements are of significant fundamental interest but are challenging because of the low surface areas involved. The relationship between the reaction zone gas flow and the pressure in the reaction zone is investigated experimentally......, it is found that platinum catalysts with areas as small as 15 mu m(2) are conveniently characterized with the device. (C) 2009 American Institute of Physics. [doi:10.1063/1.3270191]...

  16. [Sensitivity of salmonellae isolated from poultry to drugs].

    Science.gov (United States)

    Stefanov, V; Kolev, K K; Stefanov, M

    1986-01-01

    Studied were a total of 125 Salmonella strains, isolated from birds, with regard to their sensitivity to medicinal drugs. A 100 percent effect against these organisms was found with amopen, neomycin, borgal, and sumetrolin. The effect was 97.7 per cent with canamycin, gentamycin, and terramycin; it was 95.5 per cent with the use of streptomycin, spectam, and chloramphenicol, 72.4 per cent--with tetracyclin, 70.5 per cent--with nalidixic acid, and 47.7 per cent--with sulfathiazol. Resistance of the strains to carbenicillin was 83 per cent, to ampicillin--79.6 per cent, and to sulfathiazol--38.6 per cent. It was interesting to note that resistance to carbenicillin and nalidixic acid, used in human medicine only, was 82.6 and 4.54 per cent, respectively. The high susceptibility of Salmonellae to amopen, and the limited capacity of the organisms to produce resistant strains outline the perspective of its wide use in the control of Salmonella infections in birds.

  17. The effect of carbon nanotubes on drug delivery in an electro-sensitive transdermal drug delivery system.

    Science.gov (United States)

    Im, Ji S; Bai, Byong Ch; Lee, Young-Seak

    2010-02-01

    An electro-sensitive transdermal drug delivery system was prepared by the electrospinning method to control drug release. A semi-interpenetrating polymer network was prepared as the matrix with polyethylene oxide and pentaerythritol triacrylate polymers. Multi-walled carbon nanotubes were used as an additive to increase the electrical sensitivity. The release experiment was carried out under different electric voltage conditions. Carbon nanotubes were observed in the middle of the electrospun fibers by SEM and TEM. The amount of released drug was effectively increased with higher applied electric voltages. These results were attributed to the excellent electrical conductivity of the carbon additive. The suggested mechanism of drug release involves polyethylene oxide of the semi-interpenetrating polymer network being dissolved under the effects of carbon nanotubes, thereby releasing the drug. The effects of the electro-sensitive transdermal drug delivery system were enhanced by the carbon nanotubes.

  18. Analytical evaluation of five oral fluid drug testing devices

    OpenAIRE

    Isalberti, Cristina; Van Stechelman, Sylvie; Legrand, Sara-Ann; Van der Linden, Gertrude; Verstraete, Alain

    2010-01-01

    Introduction: The correlation with blood drug presence and the easiness of sample collection make oral fluid an ideal matrix for roadside drug tests targeting impaired drivers. Aim: To evaluate the reliability of five oral fluid testing devices: Varian OraLab®6, Dräger DrugTest® 5000, Cozart® DDS 806, Mavand RapidSTAT® and Innovacon OrAlert. Method: More than 760 samples were collected from volunteers either at drug addiction treatment centres or during roadside sessions. Target drug ...

  19. Information comparison of the effects of drugs on laboratory tests in drug labels and Young's book

    NARCIS (Netherlands)

    Geerts, A.F.; Koning, F.H. de; Egberts, T.C.; Smet, P.A. de; Solinge, W.W. van

    2012-01-01

    Abstract Background: The effects of drugs on laboratory tests may lead to misinterpretation of laboratory data, unnecessary tests, higher costs and missed diagnoses. This study compared the information on drug-laboratory effects (DLE) described in 200 drug labels with that in Young's book. Methods:

  20. 78 FR 52931 - Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-08-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug Substances and Products, Questions and Answers; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``ANDAs: Stability Testing of...

  1. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

  2. Drug Combinations: Tests and Analysis with Isoboles.

    Science.gov (United States)

    Tallarida, Ronald J

    2016-03-18

    Described in this unit are experimental and computational methods to detect and classify drug interactions. In most cases, this relates to two drugs or compounds with overtly similar effects, e.g., two analgesics or two anti-hypertensives. From the dose-response data of the individual drugs, it is possible to generate a curve, the isobole, which defines all dose combinations that are expected to yield a specified effect. The theory underlying the isobole involves the calculation of doses of drug A that are effectively equivalent to doses of drug B with that equivalence determining whether the isobole is linear or nonlinear. In either case, the isobole allows for a comparison with actual combination effects making it possible to determine whether the interaction is synergistic, additive, or sub-additive. Actual as well as illustrative data are employed to demonstrate experimental design and data analysis.

  3. Comparison of the sensitivities of the Buehler test and the guinea pig maximization test for predictive testing of contact allergy

    DEFF Research Database (Denmark)

    Frankild, S; Vølund, A; Wahlberg, J E;

    2001-01-01

    dose-response model. To compare the sensitivity of the 2 test procedures the test conditions were kept identical and the following chemicals with a range of sensitization potentials were tested: chloraniline, chlorhexidine, eugenol, formaldehyde, mercaptobenzothiazole and neomycin sulphate....... Formaldehyde and neomycin sulphate were strong sensitizers in both tests. Mercaptobenzothiazole, eugenol and chloraniline were all strong sensitizers in the GPMT, eugenol and mercaptobenzothiazole were negative in the Buehler test and equivocal results were obtained with chloraniline. Chlorhexidine...

  4. Overview on drug and alcohol testing in the workplace.

    Science.gov (United States)

    Hanson, M

    1993-01-01

    A flashpoint in the debate over workplace responses to alcohol and drug use by members of the workforce centres on the chemical testing of current employees and job applicants for alcohol and drug use. Drug testing may be the most contentious issue faced by enterprises struggling to develop fair and effective programmes to deal with the consequences of substance use in the workplace. The present paper examines scientific evidence on the nature and extent of alcohol and drug use by members of the workforce, evidence linking alcohol and drug use to workplace problems, workplace strategies for managing alcohol- and drug-related difficulties, and arguments for and against drug and alcohol testing. To date, the evidence supportive of alcohol and drug testing is inconclusive. Testing programmes may be useful in identifying drug users in the workforce. Their deterrent value is uncertain, however, and they are not efficient tools for linking drug users to assistance programmes. Enterprises that are contemplating establishing testing programmes should consider: (a) whether substance use is a problem in their setting; (b) whether testing will respond to the problem; (c) the costs and benefits of testing; and (d) any ethical and legal questions raised by the programmes.

  5. Interpreting IgE sensitization tests in food allergy.

    Science.gov (United States)

    Chokshi, Niti Y; Sicherer, Scott H

    2016-01-01

    Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.

  6. Signatures of Drug Sensitivity in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hua C. Gong

    2011-01-01

    Full Text Available We profiled receptor tyrosine kinase pathway activation and key gene mutations in eight human lung tumor cell lines and 50 human lung tumor tissue samples to define molecular pathways. A panel of eight kinase inhibitors was used to determine whether blocking pathway activation affected the tumor cell growth. The HER1 pathway in HER1 mutant cell lines HCC827 and H1975 were found to be highly activated and sensitive to HER1 inhibition. H1993 is a c-MET amplified cell line showing c-MET and HER1 pathway activation and responsiveness to c-MET inhibitor treatment. IGF-1R pathway activated H358 and A549 cells are sensitive to IGF-1R inhibition. The downstream PI3K inhibitor, BEZ-235, effectively inhibited tumor cell growth in most of the cell lines tested, except the H1993 and H1650 cells, while the MEK inhibitor PD-325901 was effective in blocking the growth of KRAS mutated cell line H1734 but not H358, A549 and H460. Hierarchical clustering of primary tumor samples with the corresponding tumor cell lines based on their pathway signatures revealed similar profiles for HER1, c-MET and IGF-1R pathway activation and predict potential treatment options for the primary tumors based on the tumor cell lines response to the panel of kinase inhibitors.

  7. Clinical characteristics and drug sensitivity tests of 26 cases with Staphylococcus aureus infective endocarditis%金黄色葡萄球菌心内膜炎26例的临床特点及药敏分析

    Institute of Scientific and Technical Information of China (English)

    曲云婷; 黄俊; 张黔桓; 吴书林

    2011-01-01

    Objectives To analyze the clinical characteristics of patients with Staphylococcus aureus infective endoearditis (SAIE), and to investigate the antibiotic sensitivity of Staphylococcus aureus isolates. Methods Clinical data of twenty-six patients with SAIE from January 2006 to July 2011 in Guangdong General Hospital were retrospectively analyzed. All patients met the modified Duke criteria for definite infective endocarditis. Results A total of 26 patients, 21 men and 5 women, were evaluated. Main predisposing factors were predisposing heart condition (11 patients), intravenous drug abuse (5 patients). Common clinical manifestations were fever (100%, 26/26), neurological symptoms such as headache, paralysis or unconsciousness (34.6%, 9/26), congestive heart failure(23.1%, 6/26), subcutaneous hemorrhage or rash (23.1%, 6/26) and arthralgia (19.2%, 5/26). Of all staphylococcus aureus isolates, meticillinresistant staphylococcus aureus (MRSA) accounted for 20.8 % (5/24) and the positive rate of β- lactamase was 100% (24/24). Overall rates of resistance were as follows; penicillin (96.1%, 25/26) > oxacillin(25.0%,6/24)> gentamicin (11.5%, 3/26) > teicoplanin (0,0/23),vancomycin (0,0/26), linezolid (0,0/23). Complications included cardiac and neurological complications (9 patients, respectively), multiple organ failure (2 patients), septic shock (1 patient) and pulmonary embolism (1 patient). Six patients (23.1%) died during hospitalization, and the causes were in turn neurological complications (3 patients), multiple organ failure (2 patients), septic shock (1 patient). Conclusions SAIE with various clinical manifestations are prone to neurological and cardiac complications and has a high mortality. Most strains of Staphylococcus aureus resistant to penicillin, however remain uniformly sensitive to glycopeptide antibiotics.%目的 分析金黄色葡萄球菌心内膜炎(Staphylococcus aureus infective endocarditis,SAIE)的临床及药敏特点.方法

  8. Testing for drugs of abuse in children and adolescents.

    Science.gov (United States)

    Levy, Sharon; Siqueira, Lorena M; Ammerman, Seth D; Gonzalez, Pamela K; Ryan, Sheryl A; Siqueira, Lorena M; Smith, Vincent C

    2014-06-01

    Drug testing is often used as part of an assessment for substance use in children and adolescents. However, the indications for drug testing and guidance on how to use this procedure effectively are not clear. The complexity and invasiveness of the procedure and limitations to the information derived from drug testing all affect its utility. The objective of this clinical report is to provide guidance to pediatricians and other clinicians on the efficacy and efficient use of drug testing on the basis of a review of the nascent scientific literature, policy guidelines, and published clinical recommendations.

  9. The Development and Validation of the Vocalic Sensitivity Test.

    Science.gov (United States)

    Villaume, William A.; Brown, Mary Helen

    1999-01-01

    Notes that presbycusis, hearing loss associated with aging, may be marked by a second dimension of hearing loss, a loss in vocalic sensitivity. Reports on the development of the Vocalic Sensitivity Test, which controls for the verbal elements in speech while also allowing for the vocalics to exercise their normal metacommunicative function of…

  10. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development

    DEFF Research Database (Denmark)

    Imamovic, Lejla; Sommer, Morten

    2013-01-01

    New drug deployment strategies are imperative to address the problem of drug resistance, which is limiting the management of infectious diseases and cancers. We evolved resistance in Escherichia coli toward 23 drugs used clinically for treating bacterial infections and mapped the resulting...... and select against drug resistance development. We identified hundreds of such drug sets and demonstrated that the antibiotics gentamicin and cefuroxime can be deployed cyclically such that the treatment regimen selected against resistance to either drug. We then validated our findings with related bacterial...... collateral sensitivity and resistance profiles, revealing a complex collateral sensitivity network. On the basis of these data, we propose a new treatment framework-collateral sensitivity cycling-in which drugs with compatible collateral sensitivity profiles are used sequentially to treat infection...

  11. Stressful events and psychological difficulties : Testing alternative candidates for sensitivity

    NARCIS (Netherlands)

    Laceulle, Odilia M.|info:eu-repo/dai/nl/364227885; O'Donnell, Kieran; Glover, Vivette; O'Connor, Thomas G.; Ormel, Johan; Van Aken, Marcel A G|info:eu-repo/dai/nl/081831218; Nederhof, Esther

    2014-01-01

    The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that

  12. Stressful events and psychological difficulties : testing alternative candidates for sensitivity

    NARCIS (Netherlands)

    Laceulle, Odilia M.; O'Donnell, Kieran; Glover, Vivette; O'Connor, Thomas G.; Ormel, Johan; van Aken, Marcel A. G.; Nederhof, Esther

    2014-01-01

    The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that

  13. LLNL small-scale drop-hammer impact sensitivity test

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, L.R.; Foltz, M.F.

    1995-01-01

    Small-scale safety testing of explosives and other energetic materials is done to determine their sensitivity to various stimuli including friction, static spark, and impact. This testing is typically done to discover potential handling problems for either newly synthesized materials of unknown behavior or materials that have been stored for long periods of time. This report describes the existing ``ERL Type 12 Drop Weight Impact Sensitivity Apparatus``, or ``Drop Hammer Machine``, and the methods used to determine the impact sensitivity of energetic materials, Also discussed are changes made to both the machine and methods since the inception of impact sensitivity testing at LLNL in 1956. The accumulated data for the materials tested in not listed here, the exception being the discussion of those specific materials (primary calibrants: PETN, RDX, Comp-B3,and TNT; secondary calibrants: K-6, RX-26-AF, and TATB) used to calibrate the machine.

  14. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application.

    Science.gov (United States)

    Kalita, Himani; Prashanth Kumar, B N; Konar, Suraj; Tantubay, Sangeeta; Kr Mahto, Madhusudan; Mandal, Mahitosh; Pathak, Amita

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~48 nm and 206.51 m(2)/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin.

  15. [Application of thermoplastic elastomer in hot-melt pressure sensitive adhesives for transtermal drug delivery].

    Science.gov (United States)

    Yan, Xiaoping; Zheng, Rui; Guan, Shijie; Yi, Bowen

    2009-06-01

    Development of drug dosage forms to a great extent depends on the development of drug auxiliary materials. The development of a new type of polymeric drug auxiliary materials will bring on the developing of a novel dosage forms technology and a flood of new drug dosage forms. Thermoplastic elastomer is a new type of drug polymeric auxiliary materials, at present, which has a broad application in the field of hot-melt pressure sensitive adhesives. This review mainly discussed a new transtermal Chinese drug delivery system, including matrix composition of the formula, modified thermoplastic elastomer for hot-melt pressure sensitive adhesives and their development prospects in the traditional Chinese drug delivery system. It suggested that thermoplastic elastomer of hot-melt pressure sensitive adhesives has broad development prospects in the field of the transtermal drug delivery system for traditional Chinese medicine.

  16. 碳青霉烯类抗生素耐药铜绿假单胞菌的体外联合药敏研究%Combined drug sensitivity test of carbapenem-resistant Pseudomonas aeruginosa in vitro

    Institute of Scientific and Technical Information of China (English)

    文亚坤; 曹萌; 邹琳; 罗艳萍; 孙宝君

    2012-01-01

    目的 评价环丙沙星(CIP)分别与头孢哌酮/舒巴坦(CFS)、哌拉西林/三唑巴坦(TZP)联合用药对临床分离获得的碳青霉烯类抗生素耐药的铜绿假单胞菌(CRPA)的体外抑菌作用.方法 采用棋盘法设计,琼脂平板稀释法测定抗菌药物对38株临床分离的CRPA的最低抑菌浓度(MIC),并计算抑菌指数(FIC指数)判断联合抑菌效应.结果 CIP与CFS联用后,5.3%为协同作用,81.5%为相加作用,13.2%为无关作用,没有拮抗作用;CIP与TZP联用后,7.9%为协同作用,73.7%为相加作用,18.4%为无关作用,没有拮抗作用.上述药物联用后,各药MIC50均明显降低,浓度-累积抑菌率曲线均表现为左移.结论 CIP分别与CFS、TZP联用对CRPA体外联合抗菌效应主要表现为协同和相加作用.%Objective To evaluate the combined inhibitory effect of ciprofloxacin(CIP) and cefoperazone/ sulbactam(CFS), ciprofloxacin(CIP) and piperacillin/tazobactam (TZP) respectively on clinically isolated carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains in vitro. Methods This test used chessboard method. Combined inhibitory effect of CIP and CFS, CIP and TZP in vitro was assayed by detecting the minimum inhibitory concentration and calculating the fractional inhibitory concentration (FIC) index for 38 CRPA strains with the agar dilution method. Results Combined CIP and CFS showed 5.3% synergic effect, 81.5% additive effect, 13.2% indifferent effect and no antagonistic effect on CRPA strains. Combined CIP and TZP displayed 7.9% synergic effect, 73.7% additive effect, 18.4% indifferent effect and no antagonistic effect on CRPA strains. The MIC50 of these drugs was significantly lower when they were used in combination with their concentration-accumulative curves shifted to the left. Conclusion Combined CIP and CFS, combined CIP and TZP show a combined synergic and additive inhibitory effect on CRPA strains in vitro.

  17. 75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

    Science.gov (United States)

    2010-12-20

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random... rail industry random testing positive rates were .037 percent for drugs and .014 percent for alcohol. Because the industry-wide random drug testing positive rate has remained below 1.0 percent for the last...

  18. 77 FR 75896 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2013

    Science.gov (United States)

    2012-12-26

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random.... According to data from FRA's Management Information System, the rail industry's random drug testing positive... (Administrator) has therefore determined that the minimum annual random drug testing rate for the period January...

  19. 76 FR 80781 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2012

    Science.gov (United States)

    2011-12-27

    ... Federal Railroad Administration 49 CFR Part 219 RIN 2130-AA81 Alcohol and Drug Testing: Determination of... random drug testing ] positive rate has remained below 1.0 percent for the last two years. The Federal Railroad Administrator (Administrator) has therefore determined that the minimum annual random drug testing...

  20. Hair drug testing results and self-reported drug use among primary care patients with moderate-risk illicit drug use.

    Science.gov (United States)

    Gryczynski, Jan; Schwartz, Robert P; Mitchell, Shannon Gwin; O'Grady, Kevin E; Ondersma, Steven J

    2014-08-01

    This study sought to examine the utility of hair testing as a research measure of drug use among individuals with moderate-risk drug use based on the internationally validated Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). This study is a secondary analysis using baseline data from a randomized trial of brief intervention for drug misuse, in which 360 adults with moderate-risk drug use were recruited from two community clinics in New Mexico, USA. The current study compared self-reported drug use on the ASSIST with laboratory analysis of hair samples using a standard commercially available 5-panel test with assay screening and gas chromatography/mass spectrometry (GC/MS) confirmation. Both self-report and hair testing covered a 3-month period. Overall concordance between hair testing and self-report was 57.5% (marijuana), 86.5% (cocaine), 85.8% (amphetamines), and 74.3% (opioids). Specificity of hair testing at standard laboratory cut-offs exceeded 90% for all drugs, but sensitivity of hair testing relative to self-report was low, identifying only 52.3% (127/243) of self-disclosed marijuana users, 65.2% (30/46) of cocaine users, 24.2% (8/33) of amphetamine users, and 2.9% (2/68) of opioid users. Among participants who disclosed using marijuana or cocaine in the past 3 months, participants with a negative hair test tended to report lower-frequency use of those drugs (ptesting can be useful in studies with moderate-risk drug users, but the potential for under-identification of low-frequency use suggests that researchers should consider employing low detection cut-offs and using hair testing in conjunction with self-report. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. 青海省部分地区犬与牦牛小肠结肠炎耶尔森菌的分布及药敏试验%Distribution and Drug Sensitivity Test ofYersinia enterocolitica Between Dogs and Yaks in Partial Areas of Qinghai Province

    Institute of Scientific and Technical Information of China (English)

    张红见; 曹红军; 赵静

    2013-01-01

    应用常规细菌分离培养鉴定技术对青海省部分地区犬与牦牛粪便中小肠结肠炎耶尔森菌带菌率进行检测并进行检出菌的药敏试验。结果显示,在177份样品中共检出16株小肠结肠耶尔森菌,检出率为9.04%(16/177),其中牦牛粪便中小肠结肠耶尔森菌检出率为14.04%(8/57),宠物犬粪便中的检出率为5.88%(6/102),藏獒粪便中的检出率为11.11%(2/18)。药敏试验结果显示,16株分离菌对40种药敏纸片的平均耐药率为47.19%。致病性试验表明随机选取的5株不同动物源的野生菌株对小鼠具有致死效应。%PathogenicYersinia enterocolitica were isolated in feces of dogs and yaks in Qinghai province,and drug sensitivity tests were conducted.The results showed that out of 177 samples,16 Yersinia enterocolit-ica strains were detected with a positive rate of 9.04%(16/177).The detection rates ofYersinia enteroco-litica in the feces of Yaks,dogsand Tibetan Mastiffs′were 14.04% (8/57),5.88%(6/102)and 11.11%(2/18),respectively.The results of drug sensitivity tests showed that the average drug resistance rate of 16 Yersinia enterocolitica strains was 47.19% for the 40 types of drugs tested.Whereas,5 strains of dif-ferent wild animal sources randomly selected had lethal effects to mice in pathogenic tests.

  2. Effects of antiepileptic drugs in electrophysiological tests.

    Science.gov (United States)

    Rump, S; Kowalczyk, M

    1987-01-01

    Methods of the study of antiepileptic drugs activity by means of analysis of their effects on bioelectrical ictal phenomena in the animal brain are described. The paper deals especially with EEG signal processing methods. Application of various nonparametric models (e.g. interval-amplitude scatter plots, power spectra analysis) as well as parametric models (e.g. autoregressive model, segmentation analysis) is discussed. A discriminative approach to some of these methods (especially to autoregressive model) is also presented. Special attention is stressed on the value of these methods for the study of anticonvulsant drugs activity.

  3. Establishment of a drug sensitivity panel using human lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Matsushita A

    1999-04-01

    Full Text Available We established a drug sensitivity panel consisting of 24 human lung cancer cell lines. Using this panel, we evaluated 26 anti-cancer agents: three alkylators, three platinum compounds, four antimetabolites, one topoisomerase I inhibitor, five topoisomerase II inhibitors, seven antimitotic agents and three tyrosine kinase inhibitors. This panel showed the following: a Drug sensitivity patterns reflected their clinically-established patterns of action. For example, doxorubicin and etoposide were shown to be active against small cell lung cancer cell lines and mitomycin-C and 5-fluorouracil were active against non-small cell lung cancer cell lines, in agreement with clinical data. b Correlation analysis of the mean graphs derived from the logarithm of IC50 values of the drugs gave insight into the mechanism of each drug's action. Thus, two drug combinations with reverse or no correlation, such as the combination of cisplatin and vinorelbine, might be good candidates for the ideal two drug combination in the treatment of lung cancer, as is being confirmed in clinical trials. c Using cluster analysis of the cell lines in the panel with their drug sensitivity patterns, we could classify the cell lines into four groups depending on the drug sensitivity similarity. This classification will be useful to elucidate the cellular mechanism of action and drug resistance. Thus, our drug sensitivity panel will be helpful to explore new drugs or to develop a new combination of anti-cancer agents for the treatment of lung cancer.

  4. Experiences with urine drug testing by police among people who inject drugs in Bangkok, Thailand.

    Science.gov (United States)

    Hayashi, Kanna; Ti, Lianping; Buxton, Jane A; Kaplan, Karyn; Suwannawong, Paisan; Wood, Evan; Kerr, Thomas

    2014-03-01

    Thailand has relied on drug law enforcement in an effort to curb illicit drug use. While anecdotal reports suggest that Thai police frequently use urine toxicology to identify drug users, little is known about the prevalence or impacts of this practice among people who inject drugs (IDU). Therefore, we sought to examine experiences with urine drug testing by police among IDU in Bangkok. Data were derived from a community-recruited sample of IDU in Bangkok participating in the Mitsampan Community Research Project between July and October 2011. We assessed the prevalence and correlates of being subjected to urine toxicology testing by police using multivariate Poisson regression. In total, 438 IDU participated in this study, with 293 (66.9%) participants reporting having been tested for illicit drugs by police. In multivariate analyses, reports of drug testing by police were independently and positively associated with younger age (adjusted prevalence ratio [APR]: 1.28), a history of methamphetamine injection (APR: 1.22), a history of incarceration (APR: 1.21), having been in compulsory drug detention (APR: 1.43), avoiding healthcare (APR: 1.15), and HIV seropositivity (APR: 1.19), and negatively associated with access to voluntary drug treatment (APR: 0.82) (all p<0.05). A high proportion of IDU in Bangkok were subjected to drug testing by police. Young people and methamphetamine injectors were more likely to have been tested. The findings indicate that drug testing by police is associated with the compulsory drug detention system and may be interfering with IDU's access to healthcare and voluntary drug treatment. These findings raise concern about the widespread practice of drug testing by police and its associated impacts. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. The Effectiveness of Mandatory-Random Student Drug Testing

    Science.gov (United States)

    James-Burdumy, Susanne; Goesling, Brian; Deke, John; Einspruch, Eric

    2011-01-01

    One approach some U.S. schools now use to combat high rates of adolescent substance use is school-based mandatory-random student drug testing (MRSDT). Under MRSDT, students and their parents sign consent forms agreeing to the students' participation in random drug testing as a condition of participating in athletics and other school-sponsored…

  6. Towards a pragmatic human migraine model for drug testing

    DEFF Research Database (Denmark)

    Hansen, Emma Katrine; Olesen, Jes

    2017-01-01

    BACKGROUND: A model for the testing of novel anti-migraine drugs should preferably use healthy volunteers for ease of recruiting. Isosorbide-5-mononitrate (5-ISMN) provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity...... drug testing....

  7. 78 FR 41999 - Combined Drug and Alcohol Testing Programs

    Science.gov (United States)

    2013-07-15

    ... or on-demand operators that also conduct commercial air tour operations to combine the drug and... operators to conduct separate testing programs for their commercial air tour operations. This results in an..., an operator's drug and alcohol testing program covered its commercial air tour operations. In...

  8. 77 FR 39194 - Combined Drug and Alcohol Testing Programs

    Science.gov (United States)

    2012-07-02

    ... 135 flight-for-hire and on-demand operators also conduct commercial air tours. Parts 121 and 135 each contain requirements for drug and alcohol testing and, until 2007, commercial air tour operators were... commercial air tour operators. That rule contained requirements for drug and alcohol testing for...

  9. An Assessment of Drug Testing within the Construction Industry.

    Science.gov (United States)

    Gerber, Jonathan K.; Yacoubian, George S., Jr.

    2002-01-01

    Investigates the efficacy of workplace drug-testing programs in reducing injury incident rates and workers' compensation experience-rating modification factors within the construction industry. Analyses indicate that companies with drug-testing programs experienced a 51 percent reduction in incident rates within two years of implementation.…

  10. Sensitivity Test on Precocious Line of Eimeria acervulina and Its Parent Strain to Eight Anticoccidial Drugs%堆型艾美耳球虫早熟株和母株对8种抗球虫药的敏感试验

    Institute of Scientific and Technical Information of China (English)

    李婷; 赵其平; 董辉; 韩红玉; 孔春林; 姜连连; 朱顺海; 黄兵

    2011-01-01

    [目的] 探讨堆型艾美耳球虫早熟株和母株对常用抗球虫药的敏感性.[方法] 选用地克珠利、氯苯胍、二硝托胺、癸氧喹酯、尼卡巴嗪、马杜米星、盐霉素和拉沙洛西8种抗球虫药,进行鸡体试验,通过抗球虫活性百分比(POAA)、病变记分减少率(RLS)、相对卵囊产量(ROP)和抗球虫指数(ACI)4项指标进行综合评定.[结果] 堆型艾美耳球虫早熟株和母株均对地克珠利、氯苯胍、癸氧喹酯、尼卡巴嗪、马杜米星和拉沙洛西敏感,对盐霉素轻度敏感,对二硝托胺不敏感.[结论] 遗传背景相同的虫株,其药物敏感性也相同.%[Objective] The study aimed to discuss the sensitivity of a precocious line of Eimeria acervulina and its parent strain to the conventional anticoccidial drugs. [ Method ] Eight kinds of anticoccidial drugs including diclazuril, robenidine, dinitolmide, decoquinate, nicar-bazin, maduramicin, salinomycin and lasalocidt were selected to make to test in chicken and the comprehensive evaluation was conducted on base of the 4 indexes including the percent of optimum anticoccidial activity ( POAA) , reduction of lesion scores ( RLS) , relative oocyst production ( ROP) and anticoc cidial index (ACI). [ Result] The precocious line of E. Acervulina and its parent strain were completely sensitive to diclazuril, robenidine, decoquinate, nicarbazin, maduramicin and Jasalocid, partly sensitive to salinomycin and not sensitive to dinitolmide. [ Conclusion ] The Eimeria strains with same genetic background had equal sensitivity to the drug. .

  11. Sensitivity Analysis for DHRS Heat Exchanger Performance Tests of PGSFR

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jonggan; Eoh, Jaehyuk; Kim, Dehee; Lee, Taeho; Jeong, Jiyoung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The STELLA-1 facility has been constructed and separate effect tests of heat exchangers for DHRS are going to be conducted. Two kinds of heat exchangers including DHX (shell-and-tube sodium-to-sodium heat exchanger) and AHX (helical-tube sodium-to-air heat exchanger) will be tested for design codes V and V. Main test points are a design point and a plant normal operation point of each heat exchanger. Additionally, some plant transient conditions are taken into account for establishing a test condition set. To choose the plant transient test conditions, a sensitivity analysis has been conducted using the design codes for each heat exchanger. The sensitivity of the PGSFR DHRS heat exchanger tests (the DHX and AHX in the STELLA-1 facility) has been analyzed through a parametric study using the design codes SHXSA and AHXSA at the design point and the plant normal operation point. The DHX heat transfer performance was sensitive to the change in the inlet temperature of the shell-side and the AHX heat transfer performance was sensitive to the change in the inlet temperature of the tube side. The results of this work will contribute to an improvement of the test matrix for the separate effect test of each heat exchanger.

  12. Price Sensitivity of Demand for Prescription Drugs: Exploiting a Regression Kink Design

    DEFF Research Database (Denmark)

    Simonsen, Marianne; Skipper, Lars; Skipper, Niels

    This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity....

  13. Guidelines for European workplace drug testing in oral fluid.

    Science.gov (United States)

    Cooper, Gail; Moore, Christine; George, Claire; Pichini, Simona

    2011-05-01

    Over the past decade, oral fluid has established itself as a robust testing matrix for monitoring drug use or misuse. Commercially available collection devices provide opportunities to collect and test oral fluid by the roadside and near-patient testing with both clinical and criminal justice applications. One of the main advantages of oral fluid relates to the collection of the matrix which is non-invasive, simple, and can be carried out under direct observation making it ideal for workplace drug testing. Laboratories offering legally defensible oral fluid workplace drug testing must adhere to national and international quality standards (ISO/IEC 17025); however, these standards do not address issues specific to oral fluid testing. The European Workplace Drug Testing Society (EWDTS) recognizes the importance of providing best practice guidelines to organizations offering testing and those choosing to use oral fluid drug testing to test their employees. The aim of this paper is to present the EWDTS guidelines for oral fluid workplace drug testing. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Epidemiological control of drug resistance and compensatory mutation under resistance testing and second-line therapy.

    Science.gov (United States)

    Saddler, Clare A; Wu, Yue; Valckenborgh, Frank; Tanaka, Mark M

    2013-12-01

    The fitness cost of antibiotic resistance in the absence of treatment raises the possibility that prudent use of drugs may slow or reverse the rise of resistance. Unfortunately, compensatory mutations that lower this cost may lead to entrenched resistance. Here, we develop a mathematical model of resistance evolution and compensatory mutation to determine whether reversion to sensitivity can occur, and how disease control might be facilitated by a second-line therapy. When only a single antibiotic is available, sensitive bacteria reach fixation only under treatment rates so low that hardly any cases are treated. We model a scenario in which drug sensitivity can be accurately tested so that a second-line therapy is administered to resistant cases. Before the rise of resistance to the second drug, disease eradication is possible if resistance testing and second-line treatment are conducted at a high enough rate. However, if double drug resistance arises, the possibility of disease eradication is greatly reduced and compensated resistance prevails in most of the parameter space. The boundary separating eradication from fixation of compensated resistance is strongly influenced by the underlying basic reproductive number of the pathogen and drug efficacy in sensitive cases, but depends less on the resistance cost and compensation. When double resistance is possible, the boundary is affected by the relative strengths of resistance against the two drugs in the double-resistant-compensated strain.

  15. Adenovirus replication as an in vitro probe for drug sensitivity in human tumors.

    Science.gov (United States)

    Parsons, P G; Maynard, K R; Little, J H; McLeod, G R

    1986-04-01

    The feasibility of using adenovirus 5 as an in vitro probe for chemosensitivity in short-term cultures of human tumors was evaluated using human melanoma cell lines and primary cultures of melanoma biopsies. A convenient immunoperoxidase method was developed for quantitating viral replication 2 days after infection. Two different approaches were explored: the host cell reactivation assay (HCR) using drug-treated virus; and the viral capacity assay using drug-treated cells. The HCR assay detected sensitivity to 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC) in Mer- (methyl excision repair deficient) cell lines as decreased ability of the cells to replicate MTIC-treated virus. This test should be applicable to DNA-damaging agents and repair-deficient tumors. Adenovirus replicated readily in nonproliferating primary cultures of melanoma biopsies; application of the HCR assays to this material identified one Mer- sample of 11 tested. Herpes viruses were not suitable for use in HCR because herpes simplex virus type 1 failed to distinguish Mer- from Mer+ melanoma cells; and nonproductive infection of MTIC-sensitive lymphoid cells with Epstein-Barr virus yielded an MTIC-resistant cell line. The second assay (viral capacity) involved determination of the inhibition of replication of untreated virus in treated cells. This approach correctly predicted sensitivity to hydroxyurea and deoxyadenosine in melanoma cell lines when compared with clonogenic survival assay. Viral capacity was also inhibited by cytosine arabinoside, fluorouracil, vincristine, adriamycin, 6-mercaptopurine and ionising radiation, and may therefore be useful for detecting sensitivity to a wide range of antitumor agents.

  16. European Guidelines for Workplace Drug Testing in Oral Fluid.

    Science.gov (United States)

    Brcak, Michaela; Beck, Olof; Bosch, Tessa; Carmichael, Duncan; Fucci, Nadia; George, Claire; Piper, Mark; Salomone, Alberto; Schielen, Wim; Steinmeyer, Stefan; Taskinen, Sanna; Weinmann, Wolfgang

    2017-06-28

    These guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. These guidelines are relevant to laboratory-based testing only. These guidelines follow current best practices and are constantly under review. This article is protected by copyright. All rights reserved.

  17. Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

    DEFF Research Database (Denmark)

    Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.;

    2017-01-01

    including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...... and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88...

  18. Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project.

    Science.gov (United States)

    Brunt, Tibor M; Nagy, Constanze; Bücheli, Alexander; Martins, Daniel; Ugarte, Miren; Beduwe, Cécile; Ventura Vilamala, Mireia

    2017-02-01

    Drug testing is a harm reduction strategy that has been adopted by certain countries in Europe. Drug users are able to hand in their drugs voluntarily for chemical analysis of composition and dose. Drug users will be alerted about dangerous test results by the drug testing systems directly and through warning campaigns. An international collaborative effort was launched to combine data of drug testing systems, called the Trans European Drug Information (TEDI) project. Drug testing systems of Spain, Switzerland, Belgium, Austria, Portugal, and the Netherlands participated in this project. This study presents results of some of the main illicit drugs encountered: cocaine, ecstasy and amphetamine and also comments on new psychoactive substances (NPS) detected between 2008 and 2013. A total of 45 859 different drug samples were analyzed by TEDI. The drug markets of the distinct European areas showed similarities, but also some interesting differences. For instance, purity of cocaine and amphetamine powders was generally low in Austria, whilst high in Spain and the Netherlands. And the market for ecstasy showed a contrast: whereas in the Netherlands and Switzerland there was predominantly a market for ecstasy tablets, in Portugal and Spain MDMA (3,4-methylenedioxymethamphetamine) crystals were much more prevalent. Also, some NPS appearing in ecstasy seemed more specific for one country than another. In general, prevalence of NPS clearly increased between 2008 and 2013. Drug testing can be used to generate a global picture of drug markets and provides information about the pharmacological contents of drugs for the population at risk. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Method of Testing the Flyer Sensitivity of Explosives

    Institute of Scientific and Technical Information of China (English)

    王桂吉; 赵剑衡

    2004-01-01

    By means of Mylar flyer shock explosives driven by electric gun, the method of testing the flyer initiation sensitivity of explosives is studied, and some experiments are done. The experimental results show that the test method established is correct, which is very important and instructive to study and evaluate the safety and reliability of explosives. For the moment, the test should be researched and discussed further.

  20. Urine drug testing of chronic pain patients: licit and illicit drug patterns.

    Science.gov (United States)

    Cone, Edward J; Caplan, Yale H; Black, David L; Robert, Timothy; Moser, Frank

    2008-10-01

    Chronic pain patients are frequently maintained on one or more powerful opioid medications in combination with other psychoactive medications. Urine tests provide objective information regarding patient compliance status. Little information is available on testing this unique population. The goal of this study was to characterize drug disposition patterns in urine specimens collected from a large population of pain patients. Confirmation data for 10,922 positive specimens were collated into 11 drug Classes. The number of drug/metabolites tested (#) and number of confirmed positive specimens were as follows: amphetamines (7), 160; barbiturates (5), 308; benzodiazepines (6), 2397; cannabinoids (1), 967; carisoprodol (2), 611; cocaine (1), 310; fentanyl (1), 458; meperidine (2), 58; methadone (2), 1209; opiates (7), 8996; and propoxyphene (2), 385. Subdivision into 19 distinct drug Groups allowed characterization of drug use patterns. Of the 10,922 positive specimens, 15,859 results were reported as positive in various drug Classes, and 27,197 drug/metabolites were measured by gas chromatography-mass spectrometry. The frequency of illicit drug use (cannabis, cocaine, ecstasy) was 10.8%. Being the first study of this type, these data present a large array of information on licit and illicit drug use, drug detection frequencies, drug/metabolite patterns, and multi-drug use combinations in pain patients.

  1. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

    LENUS (Irish Health Repository)

    Doherty, Ben

    2014-01-01

    KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer.

  2. Drug Testing of Student-Athletes: Another Weapon in the War against Drugs.

    Science.gov (United States)

    Russo, Charles J.; Morse, Timothy E.

    1995-01-01

    In "Acton," the Supreme Court upheld a local school board policy calling for the random, suspicionless drug testing of interscholastic student-athletes. Reviews the Court's holdings. Concludes that a drug-testing policy that is consistent with "Acton" and enjoys broad-based community support probably would be worth its expense.…

  3. Drug Testing of Student-Athletes: Another Weapon in the War against Drugs.

    Science.gov (United States)

    Russo, Charles J.; Morse, Timothy E.

    1995-01-01

    In "Acton," the Supreme Court upheld a local school board policy calling for the random, suspicionless drug testing of interscholastic student-athletes. Reviews the Court's holdings. Concludes that a drug-testing policy that is consistent with "Acton" and enjoys broad-based community support probably would be worth its expense.…

  4. Establishing relative sensitivities of various toxicity testing organisms to ammonia

    Energy Technology Data Exchange (ETDEWEB)

    Karle, L.M.; Mayhew, H.L.; Barrows, M.E.; Karls, R.K. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1994-12-31

    The toxicity of ammonia to various organisms was examined to develop a baseline for mortality in several commonly used testing species. This baseline data will assist in choosing the proper test species and in interpreting results as they pertain to ammonia. Responses for two juvenile fish species, three marine amphipods, and two species of mysid shrimp were compared for their sensitivity to levels of ammonia. All mortality caused by ammonia in the bottom-dwelling Citharichthys stigmaeus occurred within 24 h of exposure, whereas mortality in the silverside, Menidia beryllina, occurred over the entire 96-h test duration. Responses to ammonia varied among the amphipods Rhepoxynius abronius, Ampelisca abdita, and Eohaustorius estuarius. R. abronius and A. abdita showed similar sensitivity to ammonia at lower concentrations; A. abdita appeared more sensitive than R. abronius at levels above 40 mg/L. Concentrations of ammonia required to produce significant mortality in the amphipod E. estuarius were far higher than the other species examined (> 100 mg/L NH{sub 3}). A comparison of ammonia toxicity with two commonly used invertebrates, Holmesimysis sculpts and Mysidopsis bahia, suggest that these two species of mysid have similar sensitivities to ammonia. Further studies with ammonia that examine sensitivity of different organisms should be conducted to assist regulatory and environmental agencies in determining appropriate test species and in interpreting toxicological results as they may be affected by levels of ammonia.

  5. Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.

    Science.gov (United States)

    Antila, S; Järvinen, A; Akkila, J; Honkanen, T; Karlsson, M; Lehtonen, L

    1997-07-01

    Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation. In this study the possible interactions between levosimendan and ethanol in human have been studied. Twelve healthy male volunteers were included in this double-blind, randomized, cross-over study. The study consisted of three treatment periods: levosimendan 1 mg intravenously, levosimendan combined with ethanol orally and ethanol 0.8 g/kg alone. Blood samples for determination of levosimendan and ethanol concentrations were collected for 8 h after the dosing. To observe possible pharmacodynamic interactions psychomotoric tests were made before drug administration and 1h, 2h, 3h and 6h thereafter. These tests included Digit symbol substitution test, Maddox wing, Critical Flicker fusion and VAS-test for subjective assessment of performance status. Plasma levosimendan concentrations were not changed by the concomitant ethanol administration. Ethanol did not alter the pharmacokinetics of levosimendan except the volume of distribution of central compartment which was decreased. Levosimendan did neither affect elimination of ethanol. Levosimendan did not potentiate the psychomotoric effects of ethanol neither did it have any psychomotoric effects itself. In conclusion, levosimendan is not likely to have any psychomotoric adverse effects or any clinically significant interactions with ethanol.

  6. School Drug Testing: A Critical Review of the Literature

    Directory of Open Access Journals (Sweden)

    Daniel T.L. Shek

    2010-01-01

    Full Text Available This paper explores the question of whether school drug testing is an effective solution to tackle adolescent substance abuse problems. Research studies in major academic databases and Internet websites are reviewed. Several observations are highlighted from the review: (1 there are few research studies in this area, particularly in different Chinese contexts; (2 the quality of the existing studies was generally low; and (3 research findings supporting the effectiveness of school drug testing were mixed. Methodological issues underlying quantitative and qualitative evaluation studies of the effectiveness of school drug testing are also discussed.

  7. A novel flow cytometric hemozoin detection assay for real-time sensitivity testing of Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Maria Rebelo

    Full Text Available Resistance of Plasmodium falciparum to almost all antimalarial drugs, including the first-line treatment with artemisinins, has been described, representing an obvious threat to malaria control. In vitro antimalarial sensitivity testing is crucial to detect and monitor drug resistance. Current assays have been successfully used to detect drug effects on parasites. However, they have some limitations, such as the use of radioactive or expensive reagents or long incubation times. Here we describe a novel assay to detect antimalarial drug effects, based on flow cytometric detection of hemozoin (Hz, which is rapid and does not require any additional reagents. Hz is an optimal parasite maturation indicator since its amount increases as the parasite matures. Due to its physical property of birefringence, Hz depolarizes light, hence it can be detected using optical methods such as flow cytometry. A common flow cytometer was adapted to detect light depolarization caused by Hz. Synchronized in vitro cultures of P. falciparum were incubated for 48 hours with several antimalarial drugs. Analysis of depolarizing events, corresponding to parasitized red blood cells containing Hz, allowed the detection of parasite maturation. Moreover, chloroquine resistance and the inhibitory effect of all antimalarial drugs tested, except for pyrimethamine, could be determined as early as 18 to 24 hours of incubation. At 24 hours incubation, 50% inhibitory concentrations (IC50 were comparable to previously reported values. These results indicate that the reagent-free, real-time Hz detection assay could become a novel assay for the detection of drug effects on Plasmodium falciparum.

  8. [Detection of cancer, sensitivity of the test and sensitivity of the screening program].

    Science.gov (United States)

    Launoy, G; Duffy, S W; Prevost, T C; Bouvier, V

    1998-11-01

    In assessment of screening for cancer, no distinction is usually made between the sensitivity of the screening test (St) and the sensitivity of the screening program (Sp). This paper was aimed to distinguish meaning, method for assessment and interest for each of them, and to determine their relationship. Sensitivity of the screening program can be directly assessed with data from on-going trials whilst assessment of sensitivity of screening test requires modelisation techniques, especially for assessing the mean duration of the preclinical phase of cancer. Assuming an exponential distribution of this duration, lambda as the time parameter, a mathematical relation between St and Sp is suggested as follows: [formula: see text] with r being the interval between two screening tests. The implementation of this equation with data from a mass-screening program for colorectal cancer in the department of Calvados allowed us to investigate the influence of the mean preclinical phase and the interval between two screening tests on the value of the sensitivity of the screening procedure. Such a modelisation could be useful in the development of a rational screening policy.

  9. Beta blockers and the sensitivity of the thallium treadmill test

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G.J.; Henkin, R.E.; Scanlon, P.J.

    1987-09-01

    The effect beta blockers (BB) may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. Two hundred three patients over a two-year period were identified who satisfied the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. Of 58 patients with CAD not on BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent). In comparison, the sensitivity of the Th-TMT scan in the 88 patients with CAD receiving BB was 76 percent (p less than 0.05). We conclude that BB may significantly decrease the sensitivity of the Th-TMT. Physicians should fully appreciate the higher false negative rate (24 vs 10 percent) for patients on BB and consider cautious withdrawal prior to diagnostic studies.

  10. LLNL Small-Scale Friction sensitivity (BAM) Test

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, L.R.; Foltz, M.F.

    1996-06-01

    Small-scale safety testing of explosives, propellants and other energetic materials, is done to determine their sensitivity to various stimuli including friction, static spark, and impact. Testing is done to discover potential handling problems for either newly synthesized materials of unknown behavior, or materials that have been stored for long periods of time. This report describes the existing {open_quotes}BAM{close_quotes} Small-Scale Friction Test, and the methods used to determine the friction sensitivity pertinent to handling energetic materials. The accumulated data for the materials tested is not listed here - that information is in a database. Included is, however, a short list of (1) materials that had an unusual response, and (2), a few {open_quotes}standard{close_quotes} materials representing the range of typical responses usually seen.

  11. 14 CFR 120.109 - Types of drug testing required.

    Science.gov (United States)

    2010-01-01

    ... the employer's Substance Abuse Professional conducted in accordance with the provisions of 49 CFR part... CFR part 40). (a) Pre-employment drug testing. (1) No employer may hire any individual for a safety..., cocaine, opiates, phencyclidine (PCP), and amphetamines, or a metabolite of those drugs in the...

  12. Validity of Integrity Tests for Predicting Drug and Alcohol Abuse

    Science.gov (United States)

    1993-08-31

    drug-testing programs. Personnel Psvcholo-a, , 745-763. Gough, H. G. (1948). A Sociological theory of psychopathy . American Journal of Sociology, 5a...Personal Outlook Inventory. Parkridge, IL: Author. Simpson, D. D., Curtis, B., & Butler, M. C. ý1975,. Description of drug users in treatment : 1971-1972

  13. Clinical trial of a new technique for drugs of abuse testing: a new possible sampling technique.

    Science.gov (United States)

    Skoglund, Charlotte; Hermansson, Ulric; Beck, Olof

    2015-01-01

    Exhaled breath has recently been proposed as a matrix for drug testing. This study aims to further explore, develop and validate exhaled breath as a safe and effective non-invasive method for drug testing in a clinical setting. Self-reported drug use was recorded and drug testing was performed by mass spectrometry and immunochemical methods using breath, plasma and urine samples from 45 individuals voluntarily seeking treatment for recreational drug use. Cannabis was the most prevalent drug detected by any method. Urine sampling detected most cases. The exhaled breath technique was less sensitive (73%) than plasma analysis for detection of cannabis uses but captures a more recent drug intake than both plasma and urine. Exhaled breath was the preferred specimen to donate according to interview data of the participants. Testing illicit drugs with the exhaled breath sampling technique is a sufficient, non-invasive and safe alternative and complement to plasma and/or urine sampling. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Laboratory and clinical evaluation of on-site urine drug testing.

    Science.gov (United States)

    Beck, Olof; Carlsson, Sten; Tusic, Marinela; Olsson, Robert; Franzen, Lisa; Hulten, Peter

    2014-11-01

    Products for on-site urine drug testing offer the possibility to perform screening for drugs of abuse directly at the point-of-care. This is a well-established routine in emergency and dependency clinics but further evaluation of performance is needed due to inherent limitations with the available products. Urine drug testing by an on-site product was compared with routine laboratory methods. First, on-site testing was performed at the laboratory in addition to the routine method. Second, the on-site testing was performed at a dependency clinic and urine samples were subsequently sent to the laboratory for additional analytical investigation. The on-site testing products did not perform with assigned cut-off levels. The subjective reading between the presence of a spot (i.e. negative test result) being present or no spot (positive result) was difficult in 3.2% of the cases, and occurred for all parameters. The tests performed more accurately in drug negative samples (specificity 96%) but less accurately for detecting positives (sensitivity 79%). Of all incorrect results by the on-site test the proportion of false negatives was 42%. The overall agreement between on-site and laboratory testing was 95% in the laboratory study and 98% in the clinical study. Although a high degree of agreement was observed between on-site and routine laboratory urine drug testing, the performance of on-site testing was not acceptable due to significant number of false negative results. The limited sensitivity of on-site testing compared to laboratory testing reduces the applicability of these tests.

  15. Clonidine as a sensitizing agent in the forced swimming test for revealing antidepressant activity.

    OpenAIRE

    1991-01-01

    The forced swimming test (FST) in mice has failed to predict antidepressant activity for drugs having beta adrenoreceptor agonist activity and for serotonin uptake inhibitors. We investigated the potential for clonidine to render the FST sensitive to antidepressants by using a behaviorally inactive dose of this agent (0.1 mg/kg). All antidepressants studied (tricyclics, 5-HT uptake inhibitors, iprindole, mianserin, viloxazine, trazodone) showed either activity at lower doses or activity at pr...

  16. Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

    Science.gov (United States)

    Zhou, Zilan; Badkas, Apurva; Stevenson, Max; Lee, Joo-Youp; Leung, Yuet-Kin

    2015-06-20

    A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer. Herceptin, which specifically binds to HER2 antigen, was conjugated to the nanoparticles through click chemistry. The nanoparticles were characterized via dynamic light scattering (DLS) and transmission electron microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform size distribution. The pH sensitivity was assessed by drug releases and size changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug release rate accelerated and the size significantly increased. During in vitro tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed significantly increased uptake for Herceptin-conjugated nanoparticles, as compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive nanoparticles showed the highest therapeutic effect, and thus validated the efficacy of a combined approach of pH sensitivity and active targeting.

  17. New test and analysis of position-sensitive-silicon-detector

    Institute of Scientific and Technical Information of China (English)

    FENG Lang; GE Vu-Cheng; WANG He; FAN Feng-Ying; QIAO Rui; LU Fei; SONG Yu-Shou; ZHENG Tao; YE Yan-Lin

    2009-01-01

    We have tested and analyzed the properties of two-dimensional Position-Sensitive-silicon-Detector (PSD) with new integrated preamplifiers.The test demonstrates that the best position resolution for 5.5 MeV α particles is 1.7 mm (FWHM),and the best energy resolution is 2.1%,which are notably better than the previously reported results.A scaling formula is introduced to make the absolute position calibration.

  18. A hybrid approach to urine drug testing using high-resolution mass spectrometry and select immunoassays.

    Science.gov (United States)

    McMillin, Gwendolyn A; Marin, Stephanie J; Johnson-Davis, Kamisha L; Lawlor, Bryan G; Strathmann, Frederick G

    2015-02-01

    The major objective of this research was to propose a simplified approach for the evaluation of medication adherence in chronic pain management patients, using liquid chromatography time-of-flight (TOF) mass spectrometry, performed in parallel with select homogeneous enzyme immunoassays (HEIAs). We called it a "hybrid" approach to urine drug testing. The hybrid approach was defined based on anticipated positivity rates, availability of commercial reagents for HEIAs, and assay performance, particularly analytical sensitivity and specificity for drug(s) of interest. Subsequent to implementation of the hybrid approach, time to result was compared with that observed with other urine drug testing approaches. Opioids, benzodiazepines, zolpidem, amphetamine-like stimulants, and methylphenidate metabolite were detected by TOF mass spectrometry to maximize specificity and sensitivity of these 37 drug analytes. Barbiturates, cannabinoid metabolite, carisoprodol, cocaine metabolite, ethyl glucuronide, methadone, phencyclidine, propoxyphene, and tramadol were detected by HEIAs that performed adequately and/or for which positivity rates were very low. Time to result was significantly reduced compared with the traditional approach. The hybrid approach to urine drug testing provides a simplified and analytically specific testing process that minimizes the need for secondary confirmation. Copyright© by the American Society for Clinical Pathology.

  19. On the use of sensitivity tests in seismic tomography

    NARCIS (Netherlands)

    Rawlinson, N.; Spakman, W.|info:eu-repo/dai/nl/074103164

    2016-01-01

    Sensitivity analysis with synthetic models is widely used in seismic tomography as a means for assessing the spatial resolution of solutions produced by, in most cases, linear or iterative nonlinear inversion schemes. The most common type of synthetic reconstruction test is the so-called checkerboar

  20. On the use of sensitivity tests in seismic tomography

    NARCIS (Netherlands)

    Rawlinson, N.; Spakman, W.|info:eu-repo/dai/nl/074103164

    2016-01-01

    Sensitivity analysis with synthetic models is widely used in seismic tomography as a means for assessing the spatial resolution of solutions produced by, in most cases, linear or iterative nonlinear inversion schemes. The most common type of synthetic reconstruction test is the so-called

  1. On the use of sensitivity tests in seismic tomography

    NARCIS (Netherlands)

    Rawlinson, N.; Spakman, W.

    2016-01-01

    Sensitivity analysis with synthetic models is widely used in seismic tomography as a means for assessing the spatial resolution of solutions produced by, in most cases, linear or iterative nonlinear inversion schemes. The most common type of synthetic reconstruction test is the so-called checkerboar

  2. Annual banned-substance review: analytical approaches in human sports drug testing.

    Science.gov (United States)

    Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

    2017-01-01

    There has been an immense amount of visibility of doping issues on the international stage over the past 12 months with the complexity of doping controls reiterated on various occasions. Hence, analytical test methods continuously being updated, expanded, and improved to provide specific, sensitive, and comprehensive test results in line with the World Anti-Doping Agency's (WADA) 2016 Prohibited List represent one of several critical cornerstones of doping controls. This enterprise necessitates expediting the (combined) exploitation of newly generated information on novel and/or superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, and recent advances in instrumental developments. This paper is a continuation of the series of annual banned-substance reviews appraising the literature published between October 2015 and September 2016 concerning human sports drug testing in the context of WADA's 2016 Prohibited List. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Rapid recognition of drug-resistance/sensitivity in leukemic cells by Fourier transform infrared microspectroscopy and unsupervised hierarchical cluster analysis.

    Science.gov (United States)

    Bellisola, Giuseppe; Cinque, Gianfelice; Vezzalini, Marzia; Moratti, Elisabetta; Silvestri, Giovannino; Redaelli, Sara; Gambacorti Passerini, Carlo; Wehbe, Katia; Sorio, Claudio

    2013-07-21

    We tested the ability of Fourier Transform (FT) InfraRed (IR) microspectroscopy (microFTIR) in combination with unsupervised Hierarchical Cluster Analysis (HCA) in identifying drug-resistance/sensitivity in leukemic cells exposed to tyrosine kinase inhibitors (TKIs). Experiments were carried out in a well-established mouse model of human Chronic Myelogenous Leukemia (CML). Mouse-derived pro-B Ba/F3 cells transfected with and stably expressing the human p210(BCR-ABL) drug-sensitive wild-type BCR-ABL or the V299L or T315I p210(BCR-ABL) drug-resistant BCR-ABL mutants were exposed to imatinib-mesylate (IMA) or dasatinib (DAS). MicroFTIR was carried out at the Diamond IR beamline MIRIAM where the mid-IR absorbance spectra of individual Ba/F3 cells were acquired using the high brilliance IR synchrotron radiation (SR) via aperture of 15 × 15 μm(2) in sizes. A conventional IR source (globar) was used to compare average spectra over 15 cells or more. IR signatures of drug actions were identified by supervised analyses in the spectra of TKI-sensitive cells. Unsupervised HCA applied to selected intervals of wavenumber allowed us to classify the IR patterns of viable (drug-resistant) and apoptotic (drug-sensitive) cells with an accuracy of >95%. The results from microFTIR + HCA analysis were cross-validated with those obtained via immunochemical methods, i.e. immunoblotting and flow cytometry (FC) that resulted directly and significantly correlated. We conclude that this combined microFTIR + HCA method potentially represents a rapid, convenient and robust screening approach to study the impact of drugs in leukemic cells as well as in peripheral blasts from patients in clinical trials with new anti-leukemic drugs.

  4. Sensitivity of a ribavirin resistant mutant of hepatitis C virus to other antiviral drugs.

    Directory of Open Access Journals (Sweden)

    Kathleen B Mihalik

    Full Text Available BACKGROUND: While ribavirin mono-therapy regimens have minimal effect on patients with chronic hepatitis C virus (HCV infections, they can be efficacious when combined with interferon. Clinical studies show that interferon-free combination therapies containing ribavirin are also efficacious, suggesting that an interferon-free therapy could be adopted in the near future. However, generation of drug resistant mutants and cross resistance to other drugs could impair the efficacy of the treatment. Therefore, understanding the mechanism of HCV resistance to ribavirin and cross resistance to other antiviral drugs could be of major importance. METHODS: We tested the ability of a J6/JFH1 derived HCV ribavirin resistant mutant to grow in tissue cultured Huh7D cells in the presence of the mutagen 5-Fluorouracil and the nucleoside analog 2'-C-Methylcytidine. Virus replication was assessed by detecting HCV antigens by immunofluorescence and by titrating virus present in the supernatants. Recovered viruses were amplified by RT-PCR and sequenced. RESULTS: The sensitivity of HCV-RR relative to parental J6/JFH1 to the tested drugs varied. HCV-RR was more resistant than J6/JFH1 to 5-Fluorouracil but was not more resistant than J6/JFH1 to 2'-C-Methylcytidine. Growth of HCV-RR in 5-Fluorouracil allowed the selection of an HCV-RR derived mutant resistant to 5-Fluorouracil (HCV-5FU. HCV-5FU grows to moderate levels in the presence of high concentrations of 5-Fluorouracil and to parental levels in the absence of the drug. Sequence of its genome shows that HCV-5FU accumulated multiple synonymous and non-synonymous mutations. CONCLUSIONS: These results indicate that determinants of resistance to ribavirin could also confer resistance to other anti-HCV drugs, shedding light toward understanding the mechanism of action of ribavirin and highlighting the importance of combination drug selection for HCV treatment. The results also show that it is possible to select a 5

  5. Combined drug sensitivity test of carbapenem-resistant acinetobacter Baumannii%碳青霉烯耐药鲍曼不动杆菌的联合药敏研究

    Institute of Scientific and Technical Information of China (English)

    夏静静; 龚美亮; 徐雅萍; 周玉; 方向群

    2012-01-01

    目的 评价头孢哌酮/舒巴坦(CFS)与利福平(RFP)、米诺环素(MIN)及左氧氟沙星(LEV)对临床分离碳青霉烯耐药鲍曼不动杆菌(CRAB)的体外联合抑菌作用.方法 采用棋盘法设计,微量肉汤稀释法测定抗菌药物对60株临床分离的CRAB的最低抑菌浓度(MIC),并计算抑菌指数(FIC指数)判断联合抑菌效应.结果 CFS与RFP联用后,80%为协同作用,16.7%为相加作用,3.3%为无关作用,无拮抗作用;CFS与MIN联用后,11.7%为协同作用,45%为相加作用,35%为无关作用,8.3%为拮抗作用;CFS与LEV联用时,6.7%为协同作用,40%为相加作用,53.3%为无关作用,无拮抗作用.上述药物联用后,各药MIC50均明显降低,浓度-累积抑菌率曲线均表现为左移.结论 CFS与RFP、MIN联用对CRAB体外联合抗菌效应主要表现为协同和相加作用.CFS与LEV联用主要表现为无关作用,但仍有近半数菌株表现为协同和相加作用.%Objective To evaluate the combined in vitro inhibitory effect of cefoperazone/sulbactam (CFS), rifampicin (RFP), minocycline(MIN) and levofloxacin(LEV) on clinically isolated carbapenem-resistant acinetobacter Baumannii (CRAB) strains. Methods Combined in vitro inhibitory effect of CFS, RFP, MIN and LEV was assayed by detecting the maximal inhibitory concentration and calculating the fractional inhibitory concentration (FIC ) index for 60 CRAB strains with the micro-broth dilution method. Results Combined CFS and RFP showed 80% synergic effect, 16.7% additive effect, 3.3% indifferent effect and no antagonistic effect on CRAB strains. Combined CFS and MIN displayed 11.7% synergic effect, 45% additive effect, 35% indifferent effect and 8.3% antagonistic effect on CRAB strains. Combined CFS and LEV demonstrated 6.7% synergic effect, 40% additive effect, 53.3% indifferent effect and no antagonistic effect on CRAB strains. The MIC50 of these drugs was significantly lower when they were used in combination with

  6. 血培养及药敏试验后抗菌药选择合理性分析%Analysis on rationality of antibiotics choice after blood culture and drug sensitivity tests

    Institute of Scientific and Technical Information of China (English)

    姜云霞; 金柔男; 王彬; 马炜棋; 战旗

    2012-01-01

    目的 分析我院住院患者血培养中分离出的病原菌分布及耐药情况,以期指导合理应用抗菌药.方法 回顾性分析2009年10月至2010年10月230例住院患者血培养结果.结果 共检出病原菌63株.革兰阴性菌、革兰阳性菌、真菌检出率分别为80.9%、17.51%、1.59%.主要病原菌为大肠埃希菌、肺炎克雷伯菌、阴沟肠杆菌、铜绿假单胞菌,其检出率分别为20.63%、12.7%、9.52%、9.52%.粪肠球菌、表皮葡萄球菌、屎肠球菌的检出率分为9.52%、1.59%、1.59%,未发现对万古霉素耐药的葡萄球菌.大肠埃希菌及肺炎克雷伯菌产超广谱β-内酰胺酶检出率分别为6.34%、1.59%.革兰阴性菌对碳青霉烯类、阿米卡星、哌啦西林/他唑巴坦敏感性均在84%以上.结论 治疗严重的革兰阳性菌引起的血液感染可首选万古霉素等糖肽类抗菌药、治疗革兰阴性菌引起的血液感染可首选阿米卡星、β-内酰胺类/β-内酰胺酶抑制剂复方及碳青霉烯类抗菌药.%Objective To analysis the distribution and drug resistance of pathogens isolated from blood cultures in hospitalized patients in order to guide the rational application of antibiotics agents. Methods 230 cases of blood culture results in hospitalized patients during 2009 October to 2010 October were retrospectively analyzed. Results 63 strains of pathogenic bacteria were checked out. The detection rate gram-negative bacteria, gram-positive bacteria was 80.9% , 17.51% , 1.59% respectively. Main pathogenic bacteria were Escherichia coli. Klebsiella spp, Enterobacter, Pseudomonas aeruginosa, with detection rate of 20. 63% , 12. 7% , 9. 52% , 9.52% respectively. The detection rate of E. faecalis, Staphylococcus epidermidis, and E.faecium were 9. 52% , 1. 59% , 1. 59% . Detection rate of Escherichia coli and KUbsiella spp induced ESBL was 6. 34% and 1. 59% . The susceptibility of gram-negative bacteria to carbapenem, amikacin

  7. European guidelines for workplace drug testing in urine.

    Science.gov (United States)

    Taskinen, Sanna; Beck, Olof; Bosch, Tessa; Brcak, Michaela; Carmichael, Duncan; Fucci, Nadia; George, Claire; Piper, Mark; Salomone, Alberto; Schielen, Wim; Steinmeyer, Stefan; Weinmann, Wolfgang

    2017-06-01

    These European Guidelines for Workplace Drug Testing in Urine have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The first version of these urine guidelines was published in 2002. Since then, the guidelines have been followed by many laboratories in different European countries and their role has been essential particularly in countries lacking legislation for workplace drug testing. In 2014, the EWDTS started a guidelines updating project and published a new version of the urine guidelines in 2015. Here we represent this updated version of the urine guidelines. The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  8. In vitro sensitivities to antimicrobial drugs of ureaplasmas isolated from the bovine respiratory tract, genital tract and eye.

    Science.gov (United States)

    Kishima, M; Hashimoto, K

    1979-09-01

    The sensitivity to 18 antimicrobial drugs was examined for 66 strains of Ureaplasma sp isolated from respiratory tracts of calves suffering from enzootic pneumonia, urinary tracts of bulls and eyes of cows suffering from infectious bovine kerato-conjunctivitis. Furamizole, tiamulin fumarate, erythromycin lactobionate, malidomycin C, doxycycline hydrochloride, kitasamycin tartrate, tylosin tartrate, T-2636C, tetracycline hydrochloride, oxytetracycline hydrochloride, chlortetracycline hydrochloride, oleandomycin phosphate, furazolidone, spiramycin adipate, chloramphenicol and thiophenicol showed strong inhibiting activity on all the test strains. Among them, furamizole, tiamulin fumarate and erythromycin lactobionate were most active. Kanamycin sulphate showed weak activity on all the strains tested. The differences in origin of the test strains did not affect their sensitivity to any of the drugs.

  9. 78 FR 78275 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014

    Science.gov (United States)

    2013-12-26

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014 AGENCY: Federal Railroad Administration (FRA), DOT. ACTION: Notice of determination... therefore determined that the minimum annual random drug testing rate for the period January 1, 2014...

  10. Drug testing for multiemployer plans: choosing the proper legal structure.

    Science.gov (United States)

    Barlament, John L

    2004-03-01

    If drug testing of employees in a multiemployer fund must be performed, how should it be funded? This article illustrates the legal issues associated with several entities often used to fund a drug-testing program, such as health and welfare funds, apprenticeship and training funds, and labor-management cooperation committees. Without such a structure, the plan administrator and others could face unnecessary risks.

  11. 新疆石河子奶牛隐性乳房炎源金黄色葡萄球菌的分离鉴定及药物敏感性分析%Isolation, Identiifcation & Drug Sensitivity Test of Staphylococcus Aureus of Cow Recessive Mastitis in Shihezi Area, Xinjiang

    Institute of Scientific and Technical Information of China (English)

    欧都; 齐向涛; 许追; 许丹丹; 杨莉; 齐亚银

    2014-01-01

    The aim of this study was to understand biological characteristics and drug resistance of staphylococcus aureus in cow recessive mastitis from large-scale dairy farms in Shihezi region in order to provide reference to scientific prevention. Using LMT method, this experiment chose 11 large-scale dairy farms in Shihezi region to test the infection ratio of recessive mastitis and staphylococcus aureus from 313 recessive mastitis milk samples were separated and identiifed. At the same time, this experiment used the disc diffusion method (K-B method) to analyze the drug resistance of isolated bacterial strains. Research results showed that the total positive rate of cow recessive mastitis in experimental dairy farms was 44.56%(869/1950), the separation rate of staphylococcus aureus was 44.71% (93/208). Drug susceptibility test results showed that the majority of strains were highly resistant to amoxicillin, erythromycin, tetracycline, and drug resistance rate was respectively 92.30%(24/26), 80.77%(21/26), 80.77%(21/26). The samples showed sensitive to gentamicin, olfoxacin, cefazolin and the susceptibility rate was respectively 57.70%(15/26),76.92%(20/26), 76.92%(20/26). Some strains were moderately sensitive to clindamycin and the susceptibility rate was 34.62%(6/26). Thus it is suggested advice should be given according to drug sensitivity of epidemic strains when choosing antibiotics to treat cow recessive mastitis.%为了解石河子地区部分规模化奶牛场奶牛隐性乳房炎源金黄色葡萄球菌的生物学特性及药物敏感性,为科学防治该病的发生提供参考依据,本试验选择了石河子周边地区不同规模的11个奶牛场,通过采用LMT法检测其隐性乳房炎的感染率,并从采集到的313份隐性乳房炎奶样中分离鉴定金黄色葡萄球菌,同时采用纸片扩散法(K-B法)对分离株的药物敏感性进行了分析。结果表明,试验区奶牛隐性乳房炎的总阳性率为44.56%(869

  12. Direct-to-Consumer Genetic Testing and Orphan Drug Development.

    Science.gov (United States)

    Mason, Matthew; Levenson, James; Quillin, John

    2017-08-01

    Since the introduction of the Orphan Drug Act (ODA) in 1983, orphan drug approvals in the United States have jumped from testing companies. This emerging trend is the subject of this article, which begins by considering how rare-disease drugs are regulated and the rising interest in nonclinical genetic testing. It then outlines how DTC companies analyze DNA and how their techniques benefit researchers and drug developers. Then, after an overview of the current partnerships between DTCs and drug developers, it examines concerns about privacy and cost brought up by these partnerships. The article concludes by contrasting the enormous positive potential of DTC-pharma relationships and their concomitant dangers, especially to consumer privacy and cost to the healthcare system.

  13. A study of drug eruptions by provocative tests

    Directory of Open Access Journals (Sweden)

    Das J

    2001-09-01

    Full Text Available Sixty cases of drug eruptions were observed during the period of one year. The incidence of drug eruption was 0.47% amongst all Dermatology O.P.D. attendances. Male to female ratio was 7:3. The highest number of cases were seen in the age group of 21-30 years. Fixed drug eruptions were the most frequent (58.3%, followed by urticaria and angioedema (20%. The drug sulphonamides (including co-trimoxazole accounted for the highest number of eruptions (35%. The other drugs which were responsible for the eruptions, in order of frequency, were oxyphenbutazone, ampicillin, analgin, penicillin, tetracycline, ibuprofen, paracetamol, phenylbutazone, acetaminophen and phenobarbitone. The causative drug (s were confirmed by provocation tests in 42 (70% cases.

  14. Isolation and Identification of Pathogenic Bacteria from Suppurative Endometritis in Two Cases of Canine and Drug Sensitivity Test%两例犬化脓性子宫内膜炎的病原分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    何海健; 许立场

    2012-01-01

    Pathogens were studied in two cases of canine septic endometritis. With the vaginal sampling method to culture secretions of bacterial and biochemical identification, the results showed that the first cases had not been separated bacteria due to continuous use of antibiotics, and the second cases of isolated Staphylococci and Streptococci. Drug sensitivity test showed that great drug resistance has been given occasion to pathogen on canine endometritis because of too much penicillin and streptomycin clinical u-sing, while it's still sensitive to cefazolin, enrofloxacin and ciprofloxacin. They became the first selection of clinical medicine.%本研究对两例确诊为化脓性子宫内膜炎的犬进行了病原的研究.用阴道采样法采集子宫分泌物进行细菌培养和生化鉴定,结果第1例因连续使用抗生素,而分离不到细菌;第2例分离到葡萄球菌和链球菌;药敏试验结果表明,犬子宫内膜炎的主要病原菌对临床使用较多的青霉素和链霉素有很大的耐药性,而对头孢唑啉、环丙沙星、恩诺沙星等药物较为敏感,为临床首选药物.

  15. Enzyme/pH dual sensitive polymeric nanoparticles for targeted drug delivery to the inflamed colon.

    Science.gov (United States)

    Naeem, Muhammad; Kim, Wooseong; Cao, Jiafu; Jung, Yunjin; Yoo, Jin-Wook

    2014-11-01

    Novel nanoparticles whose drug release profiles are controlled by both enzyme and pH were prepared for the colon-specific drug delivery using a polymeric mixture of enzyme-sensitive azo-polyurethane and pH-sensitive Eudragit S100 (ES-Azo.pu). The enzyme/pH dual sensitive nanoparticles were designed to release a drug based on a two-fold approach which specifically aimed to target drug delivery to the inflamed colon while preventing the burst release of drugs in the stomach and small intestine. Single pH-sensitive (ES) and dual sensitive (ES-Azo.pu) nanoparticles were prepared using an oil-in-water emulsion solvent evaporation method and coumarin-6 (C-6) was used as a model drug. The successful formation of ES and ES-azo.pu nanoparticles that have 214 nm and 244 nm in mean particle size, respectively, was confirmed by scanning electron microscopy and qNano. ES nanoparticles showed almost 100% of burst drug release at pH 7.4, whereas ES-Azo.pu nanoparticles prevented the burst drug release at pH 7.4, followed by a sustained release phase thereafter. Furthermore, ES-Azo.pu nanoparticles exhibited enzyme-triggered drug release in the presence of rat cecal contents obtained from a rat model of colitis. An in vivo localization study in rat gastrointestinal tract demonstrated that ES-Azo.pu nanoparticles were selectively distributed in the inflamed colon, showing 5.5-fold higher C-6 than ES nanoparticles. In conclusion, the enzyme/pH dual sensitive nanoparticles presented in this study can serve as a promising strategy for colon-specific drug delivery against inflammatory bowel disease and other colon disorders.

  16. Rifampin Drug Resistance Tests for Tuberculosis: Challenging the Gold Standard

    Science.gov (United States)

    Aung, Kya J. M.; Bola, Valentin; Lebeke, Rossin; Hossain, Mohamed Anwar; de Rijk, Willem Bram; Rigouts, Leen; Gumusboga, Aysel; Torrea, Gabriela; de Jong, Bouke C.

    2013-01-01

    The rapid diagnosis of rifampin resistance is hampered by a reported insufficient specificity of molecular techniques for detection of rpoB mutations. Our objective for this study was to document the prevalence and prognostic value of rpoB mutations with unclear phenotypic resistance. The study design entailed sequencing directly from sputum of first failure or relapse patients without phenotypic selection and comparison of the standard retreatment regimen outcome, according to the mutation present. We found that among all rpoB mutations, the best-documented “disputed” rifampin resistance mutations (511Pro, 516Tyr, 526Asn, 526Leu, 533Pro, and 572Phe) made up 13.1% and 10.6% of all mutations in strains from Bangladesh and Kinshasa, respectively. Except for the 511Pro and 526Asn mutations, most of these strains with disputed mutations tested rifampin resistant in routine Löwenstein-Jensen medium proportion method drug susceptibility testing (DST; 78.7%), but significantly less than those with common, undisputed mutations (96.3%). With 63% of patients experiencing failure or relapse in both groups, there was no difference in outcome of first-line retreatment between patients carrying a strain with disputed versus common mutations. We conclude that rifampin resistance that is difficult to detect by the gold standard, phenotypic DST, is clinically and epidemiologically highly relevant. Sensitivity rather than specificity is imperfect with any rifampin DST method. Even at a low prevalence of rifampin resistance, a rifampin-resistant result issued by a competent laboratory may not warrant confirmation, although the absence of a necessity for confirmation needs to be confirmed for molecular results among new cases. However, a result of rifampin susceptibility should be questioned when suspicion is very high, and further DST using a different system (i.e., genotypic after phenotypic testing) would be fully justified. PMID:23761144

  17. Urine drug testing: current recommendations and best practices.

    Science.gov (United States)

    Owen, Graves T; Burton, Allen W; Schade, Cristy M; Passik, Steve

    2012-07-01

    The precise role of urine drug testing (UDT) in the practice of pain medicine is currently being defined. Confusion exists as to best practices, and even to what constitutes standard of care. A member survey by our state pain society revealed variability in practice and a lack of consensus. The authors sought to further clarify the importance of routine UDT as an important part of an overall treatment plan that includes chronic opioid prescribing. Further, we wish to clarify best practices based on consensus and data where available. A 20-item membership survey was sent to Texas Pain Society members. A group of chronic pain experts from the Texas Pain Society undertook an effort to review the best practices in the literature. The rationale for current UDT practices is clarified, with risk management strategies outlined, and recommendations for UDT outlined in detail. A detailed insight into the limitations of point-of-care (enzyme-linked immunosorbent assay, test cups, test strips) versus the more sensitive and specific laboratory methods is provided. Our membership survey was of a limited sample size in one geographic area in the United States and may not represent national patterns. Finally, there is limited data as to the efficacy of UDT practices in improving compliance and curtailing overall medication misuse. UDT must be done routinely as part of an overall best practice program in order to prescribe chronic opioid therapy. This program may include risk stratification; baseline and periodic UDT; behavioral monitoring; and prescription monitoring programs as the best available tools to monitor chronic opioid compliance.

  18. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery.

    Science.gov (United States)

    He, Chaoliang; Kim, Sung Wan; Lee, Doo Sung

    2008-05-08

    Stimuli-sensitive block copolymer hydrogels, which are reversible polymer networks formed by physical interactions and exhibit a sol-gel phase-transition in response to external stimuli, have great potential in biomedical and pharmaceutical applications, especially in site-specific controlled drug-delivery systems. The drug may be mixed with a polymer solution in vitro and the drug-loaded hydrogel can form in situ after the in vivo administration, such as injection; therefore, stimuli-sensitive block copolymer hydrogels have many advantages, such as simple drug formulation and administration procedures, no organic solvent, site-specificity, a sustained drug release behavior, less systemic toxicity and ability to deliver both hydrophilic and hydrophobic drugs. Among the stimuli in the biomedical applications, temperature and pH are the most popular physical and chemical stimuli, respectively. The temperature- and/or pH-sensitive block copolymer hydrogels for biomedical applications have been extensively developed in the past decade. This review focuses on recent development of the preparation and application for drug delivery of the block copolymer hydrogels that respond to temperature, pH or both stimuli, including poly(N-substituted acrylamide)-based block copolymers, poloxamers and their derivatives, poly(ethylene glycol)-polyester block copolymers, polyelectrolyte-based block copolymers and the polyelectrolyte-modified thermo-sensitive block copolymers. In addition, the hydrogels based on other stimuli-sensitive block copolymers are discussed.

  19. Psychometric properties of the Turkish versions of the Drug Use Disorders Identification Test (DUDIT) and the Drug Abuse Screening Test (DAST-10) in the prison setting.

    Science.gov (United States)

    Evren, Cuneyt; Ogel, Kultegin; Evren, Bilge; Bozkurt, Muge

    2014-01-01

    The aim of this study was to evaluate psychometric properties of the Drug Use Disorders Identification Test (DUDIT) and the Drug Abuse Screening Test (DAST-10) in prisoners with (n = 124) or without (n = 78) drug use disorder. Participants were evaluated with the DUDIT, the DAST-10, and the Addiction Profile Index-Short (API-S). The DUDIT and the DAST-10 were found to be psychometrically sound drug abuse screening measures with high convergent validity when compared with each other (r = 0.86), and API-S (r = 0.88 and r = 0.84, respectively), and to have a Cronbach's α of 0.93 and 0.87, respectively. In addition, a single component accounted for 58.28% of total variance for DUDIT, whereas this was 47.10% for DAST-10. The DUDIT had sensitivity and specificity scores of 0.95 and 0.79, respectively, when using the optimal cut-off score of 10, whereas these scores were 0.88 and 0.74 for the DAST-10 when using the optimal cut-off score of 4. Additionally, both the DUDIT and the DAST-10 showed good discriminant validity as they differentiated prisoners with drug use disorder from those without. Findings support the Turkish versions of both the DUDIT and the DAST-10 as reliable and valid drug abuse screening instruments that measure unidimensional constructs.

  20. Sensitivity and validity of psychometric tests for assessing driving impairment: effects of sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Stefan Jongen

    Full Text Available To assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation.Twenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am.On-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT. Large effects sizes were also found in the Divided Attention Test (DAT, the Attention Network Test (ANT, and the test for Useful Field of View (UFOV at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV.From the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use.

  1. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  2. Development of pH-sensitive self-nanoemulsifying drug delivery systems for acid-labile lipophilic drugs.

    Science.gov (United States)

    Zhao, Tianjing; Maniglio, Devid; Chen, Jie; Chen, Bin; Migliaresi, Claudio

    2016-03-01

    Oral administration is the most convenient way of all the drug delivery routes. Orally administered bioactive compounds must resist the harsh acidic fluids or enzyme digestion in stomach, to reach their absorbed destination in small intestine. This is the case for silibinin, a drug used to protect liver cells against toxins that has also been demonstrated in vitro to possess anti-cancer effects. However, as many other drugs, silibinin can degrade in the stomach due to the action of the gastric fluid. The use of pH-sensitive self-nanoemulsifying drug delivery systems (pH-SNEDDS) could overcome the drawback due to degradation of the drug in the stomach while enhancing its solubility and dissolution rate. In this paper we have investigated pH-sensitive self-nanoemulsifying formulations containing silibinin as model drug. Pseudo-ternary phase diagrams have been constructed in order to identify the self-emulsification regions under different pH. Solubility of silibinin in selected formulations has been assessed and stability of the pure drug and of the silibinin loaded pH-SNEDDS formulations in simulated gastric fluid had been compared. Droplet size of the optimized pH-SNEDDS has been correlated to pH, volume of dilution medium and silibinin loading amount. TEM (transmission electron microscopy) studies have shown that emulsion droplets had spherical shape and narrow size distribution. In vitro drug release studies of the optimal pH-SNEDDS indicated substantial increase of the drug release and release rate in comparison to pure silibinin and to the commercial silibinin tablet. The results indicated that pH-SNEDDS have potential to improve the biopharmaceutics properties of acid-labile lipophilic drugs.

  3. Computational analysis of ABL kinase mutations allows predicting drug sensitivity against selective kinase inhibitors.

    Science.gov (United States)

    Kamasani, Swapna; Akula, Sravani; Sivan, Sree Kanth; Manga, Vijjulatha; Duyster, Justus; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

    2017-05-01

    The ABL kinase inhibitor imatinib has been used as front-line therapy for Philadelphia-positive chronic myeloid leukemia. However, a significant proportion of imatinib-treated patients relapse due to occurrence of mutations in the ABL kinase domain. Although inhibitor sensitivity for a set of mutations was reported, the role of less frequent ABL kinase mutations in drug sensitivity/resistance is not known. Moreover, recent reports indicate distinct resistance profiles for second-generation ABL inhibitors. We thus employed a computational approach to predict drug sensitivity of 234 point mutations that were reported in chronic myeloid leukemia patients. Initial validation analysis of our approach using a panel of previously studied frequent mutations indicated that the computational data generated in this study correlated well with the published experimental/clinical data. In addition, we present drug sensitivity profiles for remaining point mutations by computational docking analysis using imatinib as well as next generation ABL inhibitors nilotinib, dasatinib, bosutinib, axitinib, and ponatinib. Our results indicate distinct drug sensitivity profiles for ABL mutants toward kinase inhibitors. In addition, drug sensitivity profiles of a set of compound mutations in ABL kinase were also presented in this study. Thus, our large scale computational study provides comprehensive sensitivity/resistance profiles of ABL mutations toward specific kinase inhibitors.

  4. Drug Testing in Schools: Policies, Practices, and Association with Student Drug Use. YES Occasional Papers. Paper 2

    Science.gov (United States)

    Yamaguchi, Ryoko; Johnston, Lloyd D.; O'Malley, Patrick M.

    2003-01-01

    Despite considerable recent public and judicial attention to the issue of drug testing, little empirical research has focused on the relationship between drug testing in schools and the actual use of illicit drugs by students. To explore this issue, we use school-level survey data about drug testing from the Youth, Education, and Society study and…

  5. 49 CFR 40.81 - What laboratories may be used for DOT drug testing?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What laboratories may be used for DOT drug testing... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Drug Testing Laboratories § 40.81 What laboratories may be used for DOT drug testing? (a) As a drug testing laboratory located in the U.S., you are...

  6. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Science.gov (United States)

    2010-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2010-10-01 2010-10-01 false Use of persons who fail or refuse a drug test. 199...

  7. Effect of drug physicochemical properties on drug release and their relationship with drug skin permeation behaviors in hydroxyl pressure sensitive adhesive.

    Science.gov (United States)

    Liu, Chao; Quan, Peng; Fang, Liang

    2016-10-10

    The aim of this study was to investigate the influence of drug physicochemical properties on drug release behaviors and their relationship with skin permeation behaviors, which provided transdermal enhancement strategies for the design of transdermal drug delivery system. Six model drugs with different physicochemical properties were selected and hydroxyl pressure sensitive adhesive (PSA) was synthesized. Horizontal diffusion cell was used to evaluate drug release and skin permeation behaviors. The relationship between physicochemical properties and release behaviors was conducted with regression analysis. Release behavior of 0.25% drug loading was linear related with polar surface area, which represented the hydrogen bond. Release behavior of 2.0% drug loading was dependent on the polarizability and log P, which represented dipole-dipole interaction and lipophilicity, respectively. According to the results of Fourier transform infrared spectroscopy, it was inferred that hydrogen bond was limited in controlling release of drug due to the limited quantity of bonding site, thus dipole-dipole interaction and log P became dominate control factors. Combining the drug release study and drug skin permeation study, it was concluded that drugs with different physicochemical properties should be applied with different transdermal enhancement strategies, which was useful for the design of transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Stressful events and psychological difficulties: testing alternative candidates for sensitivity.

    Science.gov (United States)

    Laceulle, Odilia M; O'Donnell, Kieran; Glover, Vivette; O'Connor, Thomas G; Ormel, Johan; van Aken, Marcel A G; Nederhof, Esther

    2014-02-01

    The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that may make children more sensitive to stressful life events. Analyses were based on data from 10,417 children from a prospective, longitudinal study of child development. At ages 4, 7, 9, 11, and 16 years, stressful events and psychological difficulties were measured. Prenatal anxiety was measured at 32 weeks of gestation and difficult temperament was measured at 6 months. Children exposed to stressful events showed significantly increased psychological difficulties at ages 7 and 11 years; there was consistent evidence of a reciprocal pattern: psychological difficulties predicted stressful events at each stage. Analyses also indicated that the associations between stressful events and psychological difficulties were stronger in girls than in boys. We found no evidence for the hypothesis that prenatal anxiety or difficult temperament increased stress sensitivity, that is, moderated the link between life events and psychological difficulties. The findings extend prior work on stress exposure and psychological difficulties and highlight the need for additional research to investigate sources of sensitivity and the mechanisms that might underlie differences in sensitivity to stressful events.

  9. Appropriate Use of Drug Testing in Clinical Addiction Medicine.

    Science.gov (United States)

    Jarvis, Margaret; Williams, Jessica; Hurford, Matthew; Lindsay, Dawn; Lincoln, Piper; Giles, Leila; Luongo, Peter; Safarian, Taleen

    : Biological drug testing is a tool that provides information about an individual's recent substance use. Like any tool, its value depends on using it correctly; that is, on selecting the right test for the right person at the right time. This document is intended to clarify appropriate clinical use of drug testing in addiction medicine and aid providers in their decisions about drug testing for the identification, diagnosis, treatment, and recovery of patients with, or at risk for, addiction. The RAND Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) process for combining scientific evidence with the collective judgment of experts was used to identify appropriate clinical practices and highlight areas where research is needed. Although consensus panels and expert groups have offered guidance on the use of drug testing for patients with addiction, very few addressed considerations for patients across settings and in different levels of care. This document will focus primarily on patients in addiction treatment and recovery, where drug testing is used to assess patients for a substance use disorder, monitor the effectiveness of a treatment plan, and support recovery. Inasmuch as the scope includes the recognition of addiction, which often occurs in general healthcare settings, selected special populations at risk for addiction visiting these settings are briefly included.

  10. Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data

    Science.gov (United States)

    Nguyen, Linh; Dang, Cuong C; Ballester, Pedro J.

    2017-01-01

    Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets, such as those by Genomics of Drug Sensitivity in Cancer (GDSC) consortium, were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF) classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC 50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than standard k-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug). Regarding overall classification performance, about two thirds of the drugs are better predicted by the multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: Thanks to this unbiased validation, we now know that this type of models can predict in vitro tumour response to some of these drugs. These models

  11. Testing the Perturbation Sensitivity of Abortion-Crime Regressions

    OpenAIRE

    2012-01-01

    The hypothesis that the legalisation of abortion contributed significantly to the reduction of crime in the United States in 1990s is one of the most prominent ideas from the recent 'economics-made-fun' movement sparked by the book Freakonomics. This paper expands on the existing literature about the computational stability of abortion-crime regressions by testing the sensitivity of coefficients' estimates to small amounts of data perturbation. In contrast to previous studies, we use a new da...

  12. Expression of cyclooxygenase-2 mRNA in drug-sensitive cell and drug-resistant strains of ovarian cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan Li; Zehua Wang

    2006-01-01

    Objective: To investigate the expression of cyclooxygenase-2 (COX-2) mRNA in drug-sensitive cell and drugresistant clones of ovarian cancer cell lines. Methods: RT-PCR and immunocytochemistry were used to investigate the expression of cyclooxygenase-2 in 3 clones drug-sensitive and 5 clones drug-resistant ovarian cancer cell. Results: Strong COX-2 mRNA expressions were detected in 3 clones of drug-sensitive cell and weak expressions were detected in 5 clones of drug-resistant cell. The protein expression of COX-2 in drug-sensitive cell was strongly positive reaction in immunocytochemistry stain and there was a weak positive reaction in 5clones of drug-resistant cell. Conclusion: The expression of COX-2 mRNA in drug-sensitive cell strains is much higher than that in drugresistant strains of ovarian cancer cell lines, providing a basis of the chemoprevention for ovarian cancer.

  13. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    Directory of Open Access Journals (Sweden)

    Valença A.M.

    2002-01-01

    Full Text Available The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2 challenge test of panic disorder (PD patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1 35% CO2 and 65% O2, and 2 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7% respiratory PD subtype patients and 5 of 11 (43.4% nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test. Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

  14. Rat gingival model for testing drugs influencing inflammation

    Directory of Open Access Journals (Sweden)

    Shaju P Jacob

    2013-07-01

    Full Text Available Preclinical drug testing is an important areain new drug development where animals are used.An ideal animal model for this is one which is simple,reliable and can be extrapolated to humans. Topicaldrugs for inflammation are conventionally tested onthe skin of animals after induction of inflammation.A gingival model would be simple as inflammation canbe induced naturally by the action of plaque. Rats area popular animal model for testing drugs as well as tostudy various diseases of the periodontium. Periodontaldisease including gingival inflammation develops inrats in relation to indigenous plaque or experimentallyinduced bacterial products. A number of features ofrats ranging from anatomy, histology and response tobacterial insult can be seen mirrored to a great extentin humans. There is a lot similarity in the developmentand resolution of inflammation as well as the gingivalwound healing of rats and humans. This paper tries toexplore the feasibility of using the rat gingival modelfor preclinical testing of drugs acting on or influencinginflammation and concludes by identifying potentialareas of research using this model. The addition of sucha simple and inexpensive model for preclinical testing ofdrugs will be welcomed by the drug developers.

  15. Army Drug Development Program. Phase 1. Clinical Testing

    Science.gov (United States)

    1981-02-01

    done as clinically indicated. * Part III of Experiment 114 was cancelled. 35 ( H+r rDrug Assay: The schedule of blood sampling will be de...Indicated. * Part III of Experiment #14 was cancelled. 79 ■■— ’( mmmm ■H-K. rDrug Assay: The schedule of blood sampling will be de...reading of phototoxicity tests. 89 tDrug Assay? 10 ml of venous blood were taXen from each sub- ject for each of 20

  16. enterotoxigenicity and drug sensitivity of staphylococci from children ...

    African Journals Online (AJOL)

    hi-tech

    2003-12-12

    Dec 12, 2003 ... children aged five years and below suffering from sporadic diarrhoea and their antibiotic susceptibility ... were isolated exclusive of other pathogens were studied further. Strains ... isolate under test and it was indicated by no change in colour .... Keersmaecker, P.H. Staphylococcus hyicus in skin lesions.

  17. Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection.

    Directory of Open Access Journals (Sweden)

    Sandip Mukherjee

    Full Text Available BACKGROUND: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug was found to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF α, IFN γ and iNOS activity increased with the concomitant decrease in IL 10 and TGF β level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. CONCLUSIONS: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar.

  18. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

    Science.gov (United States)

    Mayorga, C; Celik, G; Rouzaire, P; Whitaker, P; Bonadonna, P; Rodrigues-Cernadas, J; Vultaggio, A; Brockow, K; Caubet, J C; Makowska, J; Nakonechna, A; Romano, A; Montañez, M I; Laguna, J J; Zanoni, G; Gueant, J L; Oude Elberink, H; Fernandez, J; Viel, S; Demoly, P; Torres, M J

    2016-08-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.

  19. Ototoxic drugs: difference in sensitivity between mice and guinea pigs.

    Science.gov (United States)

    Poirrier, A L; Van den Ackerveken, P; Kim, T S; Vandenbosch, R; Nguyen, L; Lefebvre, P P; Malgrange, B

    2010-03-01

    The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to develop an adult mouse model of ototoxic drug-induced hearing loss and to compare the ototoxicity in the adult mouse to that in the well-described guinea pig model. Mice are a powerful model organism, especially due to the large availability of antibodies, probes and genetic mutants. In this study, mice (n=114) and guinea pigs (n=35) underwent systemic treatment with either kanamycin or cisplatin. Auditory brainstem responses showed a significant threshold shift in guinea pigs 2 weeks after the beginning of the ototoxic treatment, while there was no significant hearing impairment recorded in mice. Hair cells and neuronal loss were correlated with hearing function in both guinea pigs and mice. These results indicate that the mouse is not a good model for ototoxicity, which should be taken into consideration in all further investigations concerning ototoxicity-induced hearing loss.

  20. [Drug sensitivity of falciparum malaria imported into France in 1995].

    Science.gov (United States)

    Longuet, C; Ramiliarisoa, O; Thor, R; Bouchaud, O; Basco, L K; Doury, J C; Le Bras, J

    1997-01-01

    The National Reference Centre for Malaria Chemosusceptibility (CNRCP) and the Tropical Medicine Institute of the Health Department for the Army (IMTSSA) monitor the chemosusceptibility of falciparum malaria introduced in France. In 1995, 353 isolates of P. falciparum are sent to the CNRCP and IMTSSA from malaria cases presenting in 49 civil and military hospitals distributed all over the french country. The patients are mostly Africans living in France and have mainly stayed in West Africa. Half of them did not take any chemoprophylaxis and a quarter took only chloroquine more or less regularly. The curative treatment, when known, is halofantrine alone in 52% of cases and quinine alone in 28% of cases. Three halofantrine failures are reported including 1 incorrect regimen and 4 quinine failures including 3 incorrect regimens. In 1995, in vitro resistance of P. falciparum isolates imported in France to the chemoprophylactic and therapeutic drugs is not worsening. In vitro quinine resistance is rare (1/108), mefloquine resistance (2/20) and halofantrine resistance (12/211) are limited, cycloguanil resistance (42/185) is stable and chloroquine resistance (84/230) is even decreasing (less selective pressure in Africa?).

  1. Ethics and Nanopharmacy: Value Sensitive Design of New Drugs.

    Science.gov (United States)

    Timmermans, Job; Zhao, Yinghuan; van den Hoven, Jeroen

    2011-12-01

    Although applications are being developed and have reached the market, nanopharmacy to date is generally still conceived as an emerging technology. Its concept is ill-defined. Nanopharmacy can also be construed as a converging technology, which combines features of multiple technologies, ranging from nanotechnology to medicine and ICT. It is still debated whether its features give rise to new ethical issues or that issues associated with nanopharma are merely an extension of existing issues in the underlying fields. We argue here that, regardless of the alleged newness of the ethical issues involved, developments occasioned by technological advances affect the roles played by stakeholders in the field of nanopharmacy to such an extent that this calls for a different approach to responsible innovation in this field. Specific features associated with nanopharmacy itself and features introduced to the associated converging technologies- bring about a shift in the roles of stakeholders that call for a different approach to responsibility. We suggest that Value Sensitive Design is a suitable framework to involve stakeholders in addressing moral issues responsibly at an early stage of development of new nanopharmaceuticals.

  2. Fixed drug eruption by etoricoxib confirmed by patch test*

    Science.gov (United States)

    de Sousa, Aline Soares; Cardoso, José Carlos; Gouveia, Miguel Pinto; Gameiro, Ana Rita; Teixeira, Vera Barreto; Gonçalo, Maria

    2016-01-01

    Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction. PMID:27828643

  3. 49 CFR 219.701 - Standards for drug and alcohol testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

  4. Analysis of sensitivity and errors in Maglev vibration test system

    Institute of Scientific and Technical Information of China (English)

    JIANG; Dong; LIU; Xukun; WANG; Deyu; YANG; Jiaxiang

    2016-01-01

    In order to improve work performance of M aglev vibration test systems,the relationships of operating parameters between different components and system were researched. The working principle of photoelectric displacement sensor was analyzed. The relationship between displacement of transducer and the infrared light area received by sensor was given. The method of expanding the dynamic range of vibrator was proposed,which makes dynamic range of Maglev vibrator doubled. By increasing the amplification of the amplifier,the sensitive photoelectric displacement sensor can be maintained. Two modes of operation of the controller were analyzed. Bilateral work of vibration test system designed can further improve the stability of the system.An object vibration was measured by Maglev vibration test system designed when different vibration exciter frequencies were loaded. Experiments showthat the output frequency measured by Maglev vibration test system and loaded are the same. Finally,the errors of test system were analyzed. These errors of vibration test system designed can meet the requirements of application. The results laid the foundation for the practical application of magnetic levitation vibration test system.

  5. Oblique impact sensitivity of explosives: The skid test the snatch friction sensitivity test. Quarterly report, April--June 1964

    Energy Technology Data Exchange (ETDEWEB)

    Akst, I.B.; Washburn, B.M.; Rigdon, J.K.

    1997-09-01

    The oblique impact sensitivity of UK-UK-simulated HMX in 85 to 90% formulation with Viton is not enough lower, if any, to encourage richer formulations or change to Bridgewater processes for this reason alone. Fifty-pound cyclotol 75/25 hemispheres gave moderate reactions (No. 4) as low as 3.5 foot (14{degrees}); lower tests have not been performed yet. {open_quotes}Reduced-H.E.{close_quotes} pieces of PBX 9404, 2, 3, 4, and 5 inches thick, respectively, were tested at 1.75 foot (14{degrees}) resulting in a 6 reaction for the 5 inches thick piece while the remaining three pieces gave 0 reactions.

  6. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hui-Kang [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006 (China)

    2014-08-01

    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior.

  7. Road-Side Drug Testing: An Evaluation of the Alere DDS®2 Mobile Test System.

    Science.gov (United States)

    Rohrig, Timothy P; Moore, Christine M; Stephens, Kimberly; Cooper, Kelsey; Coulter, Cynthia; Baird, Tyson; Garnier, Margaux; Miller, Samuel; Tuyay, James; Osawa, Kei; Chou, Joshua; Nuss, Carson; Collier, Jeff; Wittman, Karen Cudlin

    2017-09-06

    The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however there are insufficient numbers of these highly trained drug recognition experts (DRE's) who are available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages particularly as it pertains to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory based analysis and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing; both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of a driver should still be considered the most important aspect for arrest and further action. This article is protected by copyright. All rights reserved.

  8. 濒海战创伤动物模型腹腔感染细菌学特点及药敏试验研究%Experimental study on the characteristics of bacteriology and drug sensitivity test of naval warfare injury animal model with abdominal infection

    Institute of Scientific and Technical Information of China (English)

    王代勇; 徐先锋; 唐玉娟; 王瑜; 王烈; 张再重

    2015-01-01

    目的 探讨濒海实地海水中动物模型腹部火器伤后腹腔感染的细菌学特点及其药敏试验研究.方法 将小型猪分为海水中腹部火器伤组(n=8)和陆地腹部火器伤组(n=8).海水中腹部火器伤组浸泡于海水中,在距离10 m处步枪射击左麦氏点处,继续浸泡30 min,陆地腹部火器伤组固定于陆地支架上,相同方法射击后于陆地观察30 min;之后两组行剖腹探查术,术中取腹腔液5 ml行细菌检测.细菌鉴定分析仪进行细菌学鉴定,抗菌药物敏感试验使用K-B 纸片琼脂扩散法.同时采集8份海水进行细菌鉴定.结果 两组共同检测出表皮葡萄球菌、奇异变形杆菌、大肠埃希菌等内源性肠道菌群,其中海水中腹部火器伤组检测出特有的副溶血弧菌(4%)、溶藻弧菌(8%).细菌药敏实验结果显示,对革兰阴性菌敏感率大于70%的抗菌药物包括亚胺培南、阿莫西林/克拉维酸、替卡西林/克拉维酸妥布霉素等.对革兰阳性菌敏感率大于70%的抗菌药物包括环丙沙星、达托霉素、呋喃妥因等.结论 濒海实地海水中腹部火器伤后腹腔感染为内源性肠道菌群、皮肤表面菌群和海水中特有弧菌的混合感染,故提倡早期联合使用广谱抗生素控制感染.%Objective To investigate the bacteriological characteristics and drug sensitivity test for abdominal infection of animal model after abdominal firearm injury in littoral seawater.Methods Mini-pigs were randomly divided into two groups, the group of abdominal firearm injury in littoral seawater(n=8) and the group on land (n=8).The pigs of abdominal firearm injury in littoral seawater group were soaked in sea water, and were shot from a distance of 10 m, hitting the left mcburney point, finally immersed into seawater for 30 min. Pigs in another group were fixed on fixator on land and were shot in the same way, finally observed on land for 30 min. The animals in two groups underwent exploratory

  9. Targeting CDKs with Roscovitine Increases Sensitivity to DNA Damaging Drugs of Human Osteosarcoma Cells.

    Science.gov (United States)

    Vella, Serena; Tavanti, Elisa; Hattinger, Claudia Maria; Fanelli, Marilù; Versteeg, Rogier; Koster, Jan; Picci, Piero; Serra, Massimo

    2016-01-01

    Cyclin-dependent kinase 2 (CDK2) has been reported to be essential for cell proliferation in several human tumours and it has been suggested as an appropriate target to be considered in order to enhance the efficacy of treatment regimens based on the use of DNA damaging drugs. We evaluated the clinical impact of CDK2 overexpression on a series of 21 high-grade osteosarcoma (OS) samples profiled by using cDNA microarrays. We also assessed the in vitro efficacy of the CDKs inhibitor roscovitine in a panel of drug-sensitive and drug-resistant human OS cell lines. OS tumour samples showed an inherent overexpression of CDK2, and high expression levels at diagnosis of this kinase appeared to negatively impact on clinical outcome. CDK2 expression also proved to be relevant for in vitro OS cells growth. These findings indicated CDK2 as a promising candidate therapeutic marker for OS and therefore we assessed the efficacy of the CDKs-inhibitor roscovitine in both drug-sensitive and -resistant OS cell lines. All cell lines resulted to be responsive to roscovitine, which was also able to increase the activity of cisplatin and doxorubicin, the two most active DNA damaging drugs used in OS chemotherapy. Our results indicated that combined treatment with conventional OS chemotherapeutic drugs and roscovitine may represent a new candidate intervention approach, which may be considered to enhance tumour cell sensitivity to DNA damaging drugs.

  10. 青海湖裸鲤体表白点病病原菌的分离与药敏试验%Identification and Drug Sensitivity Test of Pathogenic Bacteria of White-spot Disease From Skin Surface of Gymnocypris przewaiskii

    Institute of Scientific and Technical Information of China (English)

    李增魁; 李长忠; 康明; 圈华; 张勤文; 刘道鑫; 马东红; 夏若措毛; 李英

    2015-01-01

    To assure the pathogenic bacteria of white-spot disease from skin surface in Gymnocypris prze-waiskii and treat the disease,three bacterial strains (Citrobacter freundii ,Aeromonas veronii ,Morganella fulton)were isolated from naturally infected Gymnocypris przewaiskii and identified by morphology,cul-tural characteristics,physical and chemical characters,and 16 S rRNA sequence analysis.The three strains were Gram negative.Colony morphologies were consistent.Drug sensitivity test revealed that the three strains were highly sensitive to cefepime,amikacin and gentamicin,which will benefit the treatment of dis-ease in Gymnocypris przewaiskii .%为确定养殖青海湖裸鲤(Gymnocypris przewaiskii )体表白点病的病原,分别对患病鱼白色点状囊泡样物进行了细菌分离、生理生化特性鉴定、16 S rRNA 基因分析和药敏感试验,分离到了以弗氏柠檬酸杆菌(Citrobacter freundii )、维氏气单胞菌(Aeromonas veronii ,AV)和摩氏摩根菌(Morganella fulton )为代表的菌落形态一致、革兰阴性细菌;且分离到的3种菌都对头孢吡肟、丁胺卡那霉素、庆大霉素等药物敏感。

  11. Dissolution testing for generic drugs: an FDA perspective.

    Science.gov (United States)

    Anand, Om; Yu, Lawrence X; Conner, Dale P; Davit, Barbara M

    2011-09-01

    In vitro dissolution testing is an important tool used for development and approval of generic dosage forms. The objective of this article is to summarize how dissolution testing is used for the approval of safe and effective generic drug products in the United States (US). Dissolution testing is routinely used for stability and quality control purposes for both oral and non-oral dosage forms. The dissolution method should be developed using an appropriate validated method depending on the dosage form. There are several ways in which dissolution testing plays a pivotal role in regulatory decision-making. It may be used to waive in vivo bioequivalence (BE) study requirements, as BE documentation for Scale Up and Post Approval Changes (SUPAC), and to predict the potential for a modified-release (MR) drug product to dose-dump if co-administered with alcoholic beverages. Thus, in vitro dissolution testing plays a major role in FDA's efforts to reduce the regulatory burden and unnecessary human studies in generic drug development without sacrificing the quality of the drug products.

  12. Context-sensitive network-based disease genetics prediction and its implications in drug discovery.

    Science.gov (United States)

    Chen, Yang; Xu, Rong

    2017-04-01

    Disease phenotype networks play an important role in computational approaches to identifying new disease-gene associations. Current disease phenotype networks often model disease relationships based on pairwise similarities, therefore ignore the specific context on how two diseases are connected. In this study, we propose a new strategy to model disease associations using context-sensitive networks (CSNs). We developed a CSN-based phenome-driven approach for disease genetics prediction, and investigated the translational potential of the predicted genes in drug discovery. We constructed CSNs by directly connecting diseases with associated phenotypes. Here, we constructed two CSNs using different data sources; the two networks contain 26 790 and 13 822 nodes respectively. We integrated the CSNs with a genetic functional relationship network and predicted disease genes using a network-based ranking algorithm. For comparison, we built Similarity-Based disease Networks (SBN) using the same disease phenotype data. In a de novo cross validation for 3324 diseases, the CSN-based approach significantly increased the average rank from top 12.6 to top 8.8% for all tested genes comparing with the SBN-based approach ( pdisease using CSNs, and demonstrated that the top-ranked genes are highly relevant to PD pathologenesis. We pin-pointed a top-ranked drug target gene for PD, and found its association with neurodegeneration supported by literature. In summary, CSNs lead to significantly improve the disease genetics prediction comparing with SBNs and provide leads for potential drug targets. nlp.case.edu/public/data/. rxx@case.edu.

  13. Roche DAT immunoassay: sensitivity and specificity testing for amphetamines, cocaine, and opiates in oral fluid.

    Science.gov (United States)

    Crooks, C Richard; Brown, Sue

    2010-03-01

    Laboratory testing of oral fluid for drugs of abuse continues to expand in the workplace, legal, treatment, and health settings. In this study, we assessed recently developed homogeneous Roche DAT screening assays for amphetamines, cocaine metabolite [benzoylecgonine (BZE)], methamphetamines, and opiates in oral fluid. Precision and accuracy were assessed using control samples at +/-25% of cutoff. Sensitivity, specificity, and agreement compared to liquid chromatography-tandem mass spectrometry (LC-MS-MS) was assessed by analysis of oral fluid specimens collected from 994 subjects enrolled in a drug treatment or probation and parole drug-testing program. An additional 180 research specimens from Kroll Laboratories were analyzed for amphetamine and methamphetamine. Screening cutoff concentrations (ng/mL) were as follows: amphetamines, 40; cocaine metabolite, 3; methamphetamines, 40; and opiates, 10. LC-MS-MS analyses were performed with the following cutoff concentrations (ng/mL): amphetamine, 40; BZE, 2.0; methamphetamine, 40; and codeine or morphine, 10. The percent coefficient of variation ranged from 3.4% to 7.3%. Sensitivity and specificity of the Roche DAT assays compared to LC-MS-MS were > 94%, and agreement was > 96% for the four assays. The performance of the Roche DAT assays suggests these new homogeneous screening assays will be an attractive alternative to existing more labor-intensive enzyme immunoassays.

  14. Novel pH-sensitive biodegradable polymeric drug delivery systems based on ketal polymers.

    Science.gov (United States)

    Chen, Daquan; Wang, Hongbo

    2014-01-01

    This article reviews the recent developments on novel pH-sensitive ketal-based biodegradable polymeric drug delivery systems. Due to the degradation of ketal derivatives, neutral alcohols and ketones, ketal derivatives can be used to fabricate pH-degradable polymer with pH-degradable ketal linkages in new drug delivery systems by avoiding inflammatory problems. Due to the novelty of ketal polymers, there were few reports about ketal polymers. The review starts with a brief introduction to the pH-sensitive drug delivery system, followed by the structure, preparation and characterization techniques of ketal polymers. Thereafter, the promising applications in various diseases in relation to micro/nano drug carriers based on ketal polymers are summarized and discussed.

  15. Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Hoffner Sven

    2009-05-01

    Full Text Available Abstract Background One of the challenges facing the tuberculosis (TB control programmes in resource-limited settings is lack of rapid techniques for detection of drug resistant TB, particularly multi drug resistant tuberculosis (MDR TB. Results obtained with the conventional indirect susceptibility testing methods come too late to influence a timely decision on patient management. More rapid tests directly applied on sputum samples are needed. This study compared the sensitivity, specificity and time to results of four direct drug susceptibility testing tests with the conventional indirect testing for detection of resistance to rifampicin and isoniazid in M. tuberculosis. The four direct tests included two in-house phenotypic assays – Nitrate Reductase Assay (NRA and Microscopic Observation Drug Susceptibility (MODS, and two commercially available tests – Genotype® MTBDR and Genotype® MTBDRplus (Hain Life Sciences, Nehren, Germany. Methods A literature review and meta-analysis of study reports was performed. The Meta-Disc software was used to analyse the reports and tests for sensitivity, specificity, and area under the summary receiver operating characteristic (sROC curves. Heterogeneity in accuracy estimates was tested with the Spearman correlation coefficient and Chi-square. Results Eighteen direct DST reports were analysed: NRA – 4, MODS- 6, Genotype MTBDR® – 3 and Genotype® MTBDRplus – 5. The pooled sensitivity and specificity for detection of resistance to rifampicin were 99% and 100% with NRA, 96% and 96% with MODS, 99% and 98% with Genotype® MTBDR, and 99% and 99% with the new Genotype® MTBDRplus, respectively. For isoniazid it was 94% and 100% for NRA, 92% and 96% for MODS, 71% and 100% for Genotype® MTBDR, and 96% and 100% with the Genotype® MTBDRplus, respectively. The area under the summary receiver operating characteristic (sROC curves was in ranges of 0.98 to 1.00 for all the four tests. Molecular tests were

  16. Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA.

    Science.gov (United States)

    Ilkhani, Hoda; Hughes, Taylor; Li, Jing; Zhong, Chuan Jian; Hepel, Maria

    2016-06-15

    Widely used anti-cancer treatments involving chemotherapeutic drugs result in cancer cell damage due to their strong interaction with DNA. In this work, we have developed laboratory biosensors for screening chemotherapeutic drugs and to aid in the assessment of DNA modification/damage caused by these drugs. The sensors utilize surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods to monitor sensory film modification and observe the drug-DNA reactivity. The self-assembled monolayer protected gold-disk electrode (AuDE) was coated with a reduced graphene oxide (rGO), decorated with plasmonic gold-coated Fe2Ni@Au magnetic nanoparticles functionalized with double-stranded DNA (dsDNA), a sequence of the breast cancer gene BRCA1. The nanobiosensors AuDE/SAM/rGO/Fe2Ni@Au/dsDNA were then subjected to the action of a model chemotherapeutic drug, doxorubicin (DOX), to assess the DNA modification and its dose dependence. The designed novel nanobiosensors offer SERS/electrochemical transduction, enabling chemically specific and highly sensitive analytical signals generation. The SERS measurements have corroborated the DOX intercalation into the DNA duplex whereas the electrochemical scans have indicated that the DNA modification by DOX proceeds in a concentration dependent manner, with limit of detection LOD=8 µg/mL (S/N=3), with semilog linearity over 3 orders of magnitude. These new biosensors are sensitive to agents that interact with DNA and facilitate the analysis of functional groups for determination of the binding mode. The proposed nanobiosensors can be applied in the first stage of the drug development for testing the interactions of new drugs with DNA before the drug efficacy can be assessed in more expensive testing in vitro and in vivo.

  17. 14 CFR 120.123 - Drug testing outside the territory of the United States.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Drug testing outside the territory of the... OPERATIONS DRUG AND ALCOHOL TESTING PROGRAM Drug Testing Program Requirements § 120.123 Drug testing outside the territory of the United States. (a) No part of the testing process (including specimen collection...

  18. 21 CFR 355.70 - Testing procedures for fluoride dentifrice drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Testing procedures for fluoride dentifrice drug... Procedures § 355.70 Testing procedures for fluoride dentifrice drug products. (a) A fluoride dentifrice drug... biological tests are labeled Biological Testing Procedures for Fluoride Dentifrices; these testing procedures...

  19. Toward a pragmatic migraine model for drug testing

    DEFF Research Database (Denmark)

    Hansen, Emma Katrine; Guo, Song; Ashina, Messoud

    2016-01-01

    BACKGROUND: A model for the testing of novel antimigraine drugs should ideally use healthy volunteers for ease of recruiting. Cilostazol provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity. Therefore, this headache...

  20. NCAA Drug-Testing Program 2010-11

    Science.gov (United States)

    National Collegiate Athletic Association (NJ1), 2010

    2010-01-01

    The National Collegiate Athletic Association (NCAA) Drug-Testing Program was created to protect the health and safety of student-athletes and to ensure that no one participant might have an artificially induced advantage or be pressured to use chemical substances. This publication describes this program in the following chapters: (1) NCAA…

  1. Oral fluid for workplace drug testing: laboratory implementation.

    Science.gov (United States)

    Moore, Christine

    2012-02-01

    As oral fluid increases in popularity for workplace testing, due to its easy and observed collection, the ability to adapt existing laboratory instrumentation without further capital investment will allow more facilities to test oral fluid. The European Workplace Drug Testing Society (EWDTS) guidelines for oral fluid testing outline the maximum cut-off concentrations acceptable under the workplace drug testing programme. The recommended cut-off values may be subject to change as advances in technology or other considerations warrant identification of these substances at different concentrations; however, the instrumentation currently exists for routine screening using immunoassay and confirmation by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectral detection (LC-MS/MS) so laboratories can easily implement oral fluid analysis in their current systems. Immunoassays for the detection of the drug classes at recommended levels have been developed using various collection devices and different formats: liquid reagent chemistries and enzyme-linked immunosorbent assay (ELISA) platforms. Immunoassays provide faster turnaround than mass spectral methods particularly when the number of specimens increases. Since the guidelines state that positive immunoassay results should not be reported without confirmation, fully validated methods using LC-MS/MS and/or GC-MS for all drugs are also widely available. All proposed concentrations are easily achievable using MS instruments currently in testing laboratories; however, the likelihood of a low number of positive specimens in workplace populations allows the test facility to screen specimens in a cost-effective manner using immunoassay, while ensuring scientific credibility and defensibility by confirming the positive results with a second test. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Sensitivity of The Dynamic Visual Acuity Test To Sensorimotor Change

    Science.gov (United States)

    Cohen, Helen; Bloomberg, Jacob; Elizalde, Elizabeth; Fregia, Melody

    1999-01-01

    Post-flight astronauts, acutely post-vestibular nerve section patients, and patients with severe chronic bilateral vestibular deficits have oscillopsia caused by reduced vestibulocular reflex gains and decreased postural stability. Therefore, as previous work has shown, a test of dynamic visual acuity (DVA), in which the subject must read numbers from a computer screen while standing still or walking in place provides a composite measure of sensorimotor integration. This measure may be useful for determining the level of recovery, post-flight, post-operatively, or after vestibular rehabilitation. To determine the sensitivity of DVA to change in impaired populations we have tested patients with acoustic neuromas before and during the first post-operative week after resection of the tumors, and with bilaterally labyrinthine deficient subjects before and after six weeks of balance rehabilitation therapy.

  3. State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

    Science.gov (United States)

    Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

    2016-12-01

    The hazard assessment of skin sensitizers relies mainly on animal testing, but much progress is made in the development, validation and regulatory acceptance and implementation of non-animal predictive approaches. In this review, we provide an update on the available computational tools and animal-free test methods for the prediction of skin sensitization hazard. These individual test methods address mostly one mechanistic step of the process of skin sensitization induction. The adverse outcome pathway (AOP) for skin sensitization describes the key events (KEs) that lead to skin sensitization. In our review, we have clustered the available test methods according to the KE they inform: the molecular initiating event (MIE/KE1)-protein binding, KE2-keratinocyte activation, KE3-dendritic cell activation and KE4-T cell activation and proliferation. In recent years, most progress has been made in the development and validation of in vitro assays that address KE2 and KE3. No standardized in vitro assays for T cell activation are available; thus, KE4 cannot be measured in vitro. Three non-animal test methods, addressing either the MIE, KE2 or KE3, are accepted as OECD test guidelines, and this has accelerated the development of integrated or defined approaches for testing and assessment (e.g. testing strategies). The majority of these approaches are mechanism-based, since they combine results from multiple test methods and/or computational tools that address different KEs of the AOP to estimate skin sensitization potential and sometimes potency. Other approaches are based on statistical tools. Until now, eleven different testing strategies have been published, the majority using the same individual information sources. Our review shows that some of the defined approaches to testing and assessment are able to accurately predict skin sensitization hazard, sometimes even more accurate than the currently used animal test. A few defined approaches are developed to provide an

  4. A short-term in vitro test for tumour sensitivity to adriamycin based on flow cytometric DNA analysis

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1983-01-01

    A new method to test the sensitivity of tumour cells to chemotherapy is presented. Tumour cells were incubated in vitro on agar, and drug-induced cell cycle perturbation was monitored by flow cytometric DNA analysis. In the present study the method was applied to monitor the effect of adriamycin...

  5. 21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

    Science.gov (United States)

    2010-04-01

    ... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

  6. Phenylephrine induced fixed drug eruption: a rare case of cross sensitivity

    Directory of Open Access Journals (Sweden)

    Mahesh Chander Gupta

    2016-08-01

    Full Text Available Fixed drug eruption (FDE is a type of dermatosis characterized by recurrent lesions at exactly the same sites with each administration of the causative agents. FDEs are common types of drug eruptions amongst all cutaneous drug-induced side effects, mostly by intermittent exposure. Multiple drugs with common chemical structure can cause same type of lesions at same site called as cross sensitivity. There are many causative agents and the incidence of FDEs for a particular drug depends on the frequency of its use. Though usually not severe or fatal, cosmetic embarrassment is main problem, especially when they recur on the previously affected sites leaving behind residual hyperpigmentation. Phenylephrine is a sympathomimetic agent, given orally for the symptomatic relief of nasal congestion. It is also commonly combined with other ingredients in preparations intended for the relief of cough and cold symptoms. Considering the frequent use of Phenylephrine, associated drug eruptions generally appear to be rare, cross sensitivity with pseudoephedrine is even rarer. In our case phenylepherine was self-administered to control cold induced congestion and patient developed FDE on vermillion of upper lip, which healed after 2 weeks leaving hyperpigmentation and reappear on same site after re-challenge also. She has history of FDEs due to pseudoephedrine on same site on lips. This is a rare case of sympathomimetics induced FDE with cross sensitivity between phenylepherine and pseudoephedrine; hence we are reporting it here. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1687-1690

  7. Characterization of drug release and diffusion mechanism through hydroxyethylmethacrylate/methacrylic acid pH-sensitive hydrogel.

    Science.gov (United States)

    Varshosaz, Jaleh; Hajian, Mahmood

    2004-01-01

    Hydroxyethylmethacrylate/methacrylic acid copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk free radical polymerization method. The permeability studies of this pH-sensitive hydrogel to drugs with different water solubilities showed a water-content dependent diffusion or pore mechanism for ephedrine HCl (water-soluble model drug), whereas, a partition or solute-diffusion mechanism for indomethacin (a water-insoluble drug) was seen. Data analysis of release tests, according to the swelling interface number and Peppas equation for ephedrine HCl in pH 7.4, showed a biexponential model kinetic, whereas in pH 1.2 a swelling-controlled mechanism was seen. Indomethacin was released by an anomalous or non-Fickian release kinetics.

  8. Drug-induced exanthems: correlation of allergy testing with histologic diagnosis.

    Science.gov (United States)

    Seitz, Cornelia S; Rose, Christian; Kerstan, Andreas; Trautmann, Axel

    2013-11-01

    Skin biopsies are commonly performed to confirm drug-induced exanthem (DIE). However, the relevance of histologic examination in discriminating between DIE and non-DIE (NDIE) is controversial. A retrospective analysis was performed to evaluate the reliability of histologic diagnosis of DIE. In all, 91 patients with a skin biopsy specimen of an acute exanthem temporally related to a single identifiable drug underwent complete allergy testing. Their biopsy specimens were retrospectively re-evaluated by 2 dermatopathologists blinded to the original reports to test for discrimination between DIE versus NDIE. In 35 patients, non-IgE-mediated drug allergy was confirmed by allergy testing, whereas in 56 patients drug hypersensitivity could be excluded. Sensitivity of pathology reports for diagnosis of DIE reached 62.9% with a positive predictive value of 40.7%. Specificity was 41.1% with a negative predictive value of 69.7%. No significant difference in tissue eosinophilia was detected between DIE and NDIE. This was a retrospective study. Dermatopathologic evaluation of skin biopsy specimens is of limited use in differentiating between DIE and NDIE. All efforts should be made to subject these patients to thorough allergy testing for definitely confirming or ruling out drug hypersensitivity. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  9. HRPII双抗夹心ELISA检测恶性疟原虫体外敏感性研究%Drug sensitivity test of Plasmodium falciparum to antimalarias in vitro by using histidine-rich protein 2 double-site sandwich enzyme-linked immunosorbent assay

    Institute of Scientific and Technical Information of China (English)

    黄芳; 冯晓平; 周水森; 汤林华

    2009-01-01

    目的 验证富组蛋白2双抗夹心酶联免疫吸附法(Histidine-Rich Protein 2 Double-Site Sandwich Enzyme-Linked Immunosorbent Assay,HRPII-ELISA)在恶性疟原虫体外敏感性检测中的适用性.方法 运用HRPII-ELISA测定氯喹、咯萘啶、青蒿琥酯、蒿甲醚及双氢青蒿素等五种抗疟药物对体外培养的恶性疟原虫氯喹敏感株与氯喹抗性株的体外敏感性,并对所测得的量效曲线(dose-respense curves)及50%有效抑制浓度(IC50)与WHO推荐的Riekmann体外微量法比较.结果 HRPII-ELISA法测定的五种药物对恶性疟原虫氯喹敏感株的IC50值依次为4.7 nmol/L、2.90nmol/L、3.38nmol/L、4.64nmol/L、2.72nmol/L,对恶性疟原虫氯喹抗性株的IC50值依次为110.4nmol/L、3.85n mol/L、4.39nmol/L、3.90nmol/L、3.27nmol/L;同时,将上述结果与体外微量法所得的结果进行相关性分析,R2=0.96,P<0.001,两种方法结果基本一致.结论 HRPII-ELISA法可用于恶性疟原虫对抗疟药物的体外敏感性检测.%Objective To determine the feasibility of histidine-fich protein 2 double-site sandwich enzyme-linked immunosorbont assay for in vitro testing sensitivity of Plasmodium falciparum to antimalrials. Methods The dose-response curves and the effective concentration that resulted in a 50% inhibitory of parasitemia (IC50) of chloroquine,pyronaridine phosphate,artesunate,artemether,dihydroartemisinin against Plasmodium falciparum strain FCC1/HN and FCCSM/YN cultured in vitro tested by HRPII-ELISA were compared with those determined by Rieckmann's in vitro micro-technique recommeded by WHO. Results The IC50 of above drugs to chloroquine sensitive Plasmodium falciparum were 4.7 n mol/L, 2.90 n mol/L,3.12 n mol/L,4.30 n mol/L and 2.18 n mol/L respectively. While the IC50 to chloroquine-resistant Plasmodium falciparum were110.4 n mol/L,3.87 n mol/L,4.31n mol/L,3.90 n mol/L and 3.17 n mol/L. And the results of both techniques are similar or identical by correlation analysis (R2

  10. Testing a fall risk model for injection drug users.

    Science.gov (United States)

    Pieper, Barbara; Templin, Thomas N; Goldberg, Allon

    2012-01-01

    Fall risk is a critical component of clinical assessment and has not been examined for persons who have injected illicit drugs and are aging. The aim of this study was to test and develop the Fall Risk Model for Injection Drug Users by examining the relationships among injection drug use, chronic venous insufficiency, lower extremity impairments (i.e., decreased ankle range of motion, reduced calf muscle endurance, and leg pain), age and other covariates, and the Tinetti balance and gait total score as a measure of fall risk. A cross-sectional comparative design was used with four crossed factors. Standardized instruments were used to assess the variables. Moderated multiple regression with linear and quadratic trends in age was used to examine the nature of the relationship between the Tinetti balance and gait total and age and the potential moderating role of injection drug use. A prespecified series of models was tested. Participants (n = 713) were men (46.9%) and women with a mean age of 46.26 years and primarily African American (61.7%) in methadone treatment centers. The fall risk of a 48-year-old leg injector was comparable with the fall risk of a 69-year-old who had not injected drugs. Variables were added to the model sequentially, resulting in some lost significance of some when they were explained by subsequent variables. Final significant variables in the model were employment status, number of comorbidities, ankle range of motion, leg pain, and calf muscle endurance. Fall risk was associated with route of drug use. Lower extremity impairments accounted for the effects of injection drug use and chronic venous insufficiency on risk for falls. Further understanding of fall risk in injection users is necessary as they age, attempt to work, and participate in activities.

  11. Heat Shock Protein translocation induced by membrane fluidization increases tumor-cell sensitivity to chemotherapeutic drugs.

    Science.gov (United States)

    Dempsey, Nina C; Ireland, H Elyse; Smith, Carly M; Hoyle, Christine F; Williams, John H H

    2010-10-28

    Treatment of chronic lymphocytic leukemia (CLL) remains a challenge due to the frequency of drug resistance amongst patients. Improving the delivery of chemotherapeutic agents while reducing the expression of anti-apoptotic Heat Shock Proteins (HSPs) within the cancer cells may facilitate in overcoming this drug resistance. We demonstrate for the first time that sub-lethal doses of chemotherapeutic agents can be combined with membrane fluidizing treatments to produce a significant increase in drug efficacy and apoptosis in vitro. We show that fluidizers result in a transient decrease in intracellular HSPs, resulting in increased tumor-cell sensitivity and a membrane-associated induction of HSP gene expression.

  12. Odor-Specific Loss of Smell Sensitivity with Age as Revealed by the Specific Sensitivity Test.

    Science.gov (United States)

    Seow, Yi-Xin; Ong, Peter K C; Huang, Dejian

    2016-07-01

    The perception of odor mixtures plays an important role in human food intake, behavior, and emotions. Decline of smell acuity with normal aging could impact food perception and preferences at various ages. However, since the landmark Smell Survey by National Geographic, little has been elucidated on differences in the onset and extent of loss in olfactory sensitivity toward single odorants. Here, using the Specific Sensitivity test, we show the onset and extent of loss in both identification and detection thresholds of odorants with age are odorant-specific. Subjects of Chinese descent in Singapore (186 women, 95 men), aged 21-80 years, were assessed for olfactory sensitivity of 10 odorants from various odor groups. Notably, subjects in their 70s required 179 times concentration of rose-like odorant (2-phenylethanol) than subjects in the 20s, while thresholds for onion-like 2-methyloxolane-3-thiol only differed by 3 times between the age groups. In addition, identification rate for 2-phenylethanol was negatively correlated with age throughout adult life whereas mushroom-like oct-1-en-3-ol was equally identified by subjects across all ages. Our results demonstrated the girth of differentiated olfactory loss due to normal ageing, which potentially affect overall perception and preferences of odor mixtures with age. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Evaluation of on-site oral fluid screening using Drugwipe-5(+), RapidSTAT and Drug Test 5000 for the detection of drugs of abuse in drivers.

    Science.gov (United States)

    Wille, Sarah M R; Samyn, Nele; Ramírez-Fernández, Maria del Mar; De Boeck, Gert

    2010-05-20

    Driving under the influence of drugs is a major problem worldwide. At the moment, several countries have adopted a 'per se' legislation to address this problem. One of the key elements in the enforcement process is the possibility of rapid on-site screening tests to take immediate administrative measures. In this study, the reliability of three oral fluid screening devices (Mavand RapidSTAT, Securetec Drugwipe-5(+), and Dräger DrugTest 5000) was assessed by comparing their on-site results with confirmatory GC-MS plasma analysis. Our results demonstrate that for amphetamine screening, the oral fluid on-site devices on the market today are certainly sensitive enough. RapidSTAT, Drugwipe-5(+), and DrugTest 5000 demonstrated respectively a sensitivity of 93%, 100% and 92% for amphetamine/MDMA. For cocaine screening, sensitivities of 75%, 78% and 67% were obtained for the RapidSTAT, Drugwipe-5(+), and DrugTest 5000 devices, respectively. The studied devices were able to detect about 70% of all cannabis users in a roadside setting. However, a newer version of the DrugTest 5000 test cassette demonstrated a sensitivity of 93%, indicating an increased detection of Delta(9)-tetrahydrocannabinol using 'new generation' oral fluid screening tests with lowered cut-offs. Due to these promising results police officers and judicial experts are keen to use oral fluid screening devices. They believe that their ease of use and diminished amount of false positive results in comparison with urine screening will lead to more roadside tests and more appropriate juridical measures.

  14. Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

    Science.gov (United States)

    Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

    2016-07-01

    Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Testing for diabetes in hospitalised patients prescribed antipsychotic drugs.

    Science.gov (United States)

    Taylor, David; Young, Corina; Esop, Raadiyya; Paton, Carol; Walwyn, Rebecca

    2004-08-01

    Studies using computer databases suggest that atypical antipsychotic agents are more likely to be associated with diabetes than are conventional drugs. To discover the extent of testing for diabetes mellitus in hospital in-patients prescribed antipsychotics. Prescription charts were screened to identify patients prescribed antipsychotics. Case notes were then searched for evidence of testing for diabetes. In all, 606 patients were prescribed antipsychotics, of whom 250 (41.3%) had evidence of prior testing for diabetes. Patients prescribed atypicals were 40% more likely to have been tested than those prescribed conventional drugs (RR =1.4,95% CI1.1-1.9). Adjusted odds ratios v. conventional antipsychotics for conventional antipsychotics for testing were significantly higher for clozapine (OR=4.64,95% CI 2.42-8.90), olanzapine (OR=1.85,95% CI1.04-3.30) and antipsychotic polypharmacy (OR=2.96,95% CI1.59-5.52). Testing for diabetes was undertaken in less than half of the patients studied. Testing was more common in those receiving atypical antipsychotics. Apparent differences in claimed causal association of the use of some antipsychotics with diabetes may in part reflect different rates of testing.

  16. Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps.

    Science.gov (United States)

    Basu, Reetobrata; Baumgaertel, Nicholas; Wu, Shiyong; Kopchick, John J

    2017-03-14

    Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action. We found that GH treatment of human melanoma cells upregulates expression of multiple ABC transporters and increases the EC50 of melanoma drug vemurafenib. Also, vemurafenib-resistant melanoma cells had upregulated levels of GH receptor (GHR) expression as well as ABC efflux pumps. GHR knockdown (KD) using siRNA in human melanoma cells treated with sub-EC50 doses of anti-tumor compounds resulted in significantly increased drug retention, decreased cell proliferation and increased drug efficacy, compared to mock-transfected controls. Our set of findings identify an unknown mechanism of GH regulation in mediating melanoma drug resistance and validates GHR as a unique therapeutic target for sensitizing highly therapy-resistant human melanoma cells to lower doses of anti-cancer drugs.

  17. Insulin-like growth factor 2 silencing restores taxol sensitivity in drug resistant ovarian cancer.

    Science.gov (United States)

    Brouwer-Visser, Jurriaan; Lee, Jiyeon; McCullagh, KellyAnne; Cossio, Maria J; Wang, Yanhua; Huang, Gloria S

    2014-01-01

    Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated in vitro and in vivo. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone.

  18. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  19. 49 CFR 40.87 - What are the cutoff concentrations for drug tests?

    Science.gov (United States)

    2010-10-01

    ... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Drug Testing Laboratories § 40.87 What are the cutoff concentrations for drug tests? (a) As a laboratory, you must use the cutoff concentrations displayed in the... 49 Transportation 1 2010-10-01 2010-10-01 false What are the cutoff concentrations for drug tests...

  20. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  1. Nevirapine patch testing in Thai human immunodeficiency virus infected patients with nevirapine drug hypersensitivity.

    Science.gov (United States)

    Prasertvit, Piyatida; Chareonyingwattana, Angkana; Wattanakrai, Penpun

    2017-08-06

    Antiretroviral drug hypersensitivity in HIV patients is common. Publications have shown that Abacavir (ABC) patch testing is useful in confirming ABC hypersensitivity in 24-50% of cases with a 100% sensitivity of HLA-B*5701 in patch test positive cases. However, Nevirapine (NVP) patch testing has not been reported. (1) To evaluate the usefulness and safety of NVP patch testing in Thai HIV patients with NVP hypersensitivity. (2) To assess the correlation of positive patch tests with HLA-B*3505. Patients were classified into two groups: (1) study group of 20 HIV NVP hypersensitivity patients and (2) control group of 15 volunteers without NVP hypersensitivity. Both groups were patch tested with purified and commercialized form of NVP in various vehicles. Two HIV patients with NVP hypersensitivity were patch test positive. All controls tested negative. Three HIV patients were positive for HLA-B*3505 and the two patients with positive patch testing were both HLA-B*3505 positive. NVP patch testing in Thai HIV patients is safe and can be used to help confirm the association between NVP and hypersensitivity skin reactions. NVP patch test results significantly correlated with HLA-B*3505. The sensitivity of HLA-B*3505 for positive patch test was 100%. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. 75 FR 59105 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs: Federal Drug Testing...

    Science.gov (United States)

    2010-09-27

    ... modifications. As a reminder to MROs, the ``Test Cancelled'' box should only be used when the split fails to....187(f) rule text on how MROs are to document split specimen results. It is our understanding that...

  3. Antagonism of HSV-tk transfection and ganciclovir treatment on chemotherapeutic drug sensitivity

    NARCIS (Netherlands)

    Van Dillen, IJ; Mulder, NH; Meijer, C; Dam, WA; Kamstra, E; De Vries, L; Meersma, GJ; Van Der Zee, AGJ; De Vries, EFJ; Vaalburg, W; Hospers, GAP

    Our study focused on the influence of herpes simplex virus thymidine kinase (HSV-tk) expression and ganciclovir (GCV) treatment on the sensitivity of C6 glioma cells to frequently used chemotherapeutic drugs, i.e. adriamycin (ADR), cisplatin (CDDP), 5-fluorouracil (5-FU), and methotrexate (MTX).

  4. Mouse models for pre-clinical drug testing in leukemia.

    Science.gov (United States)

    Bhatia, Sanil; Daschkey, Svenja; Lang, Franziska; Borkhardt, Arndt; Hauer, Julia

    2016-11-01

    The development of novel drugs which specifically target leukemic cells, with the overall aim to increase complete remission and to reduce toxicity and morbidity, is the most important prerequisite for modern leukemia treatment. In this regard, the current transition rate of potential novel drugs from bench to bedside is remarkably low. Although many novel drugs show promising data in vitro and in vivo, testing of these medications in clinical phase I trials is often sobering with intolerable toxic side effects leading to failure in FDA approval. Areas covered: In this review, the authors discuss the development of murine model generation in the context of targeted therapy development for the treatment of childhood leukemia, aiming to decrease the attrition rate of progressively complex targeted therapies ranging from small molecules to cell therapy. As more complex therapeutic approaches develop, more complex murine models are needed, to recapitulate closely the human phenotype. Expert opinion: Combining xenograft models for efficacy testing and GEMMs for toxicity testing will be a global approach for pre-clinical testing of complex therapeutics and will contribute to the clinical approval of novel compounds. Finally, this approach is likely to increase clinical approval of novel compounds.

  5. Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

    Science.gov (United States)

    Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

    2015-02-01

    Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

  6. Testing the Perturbation Sensitivity of Abortion-Crime Regressions

    Directory of Open Access Journals (Sweden)

    Michał Brzeziński

    2012-06-01

    Full Text Available The hypothesis that the legalisation of abortion contributed significantly to the reduction of crime in the United States in 1990s is one of the most prominent ideas from the recent “economics-made-fun” movement sparked by the book Freakonomics. This paper expands on the existing literature about the computational stability of abortion-crime regressions by testing the sensitivity of coefficients’ estimates to small amounts of data perturbation. In contrast to previous studies, we use a new data set on crime correlates for each of the US states, the original model specifica-tion and estimation methodology, and an improved data perturbation algorithm. We find that the coefficients’ estimates in abortion-crime regressions are not computationally stable and, therefore, are unreliable.

  7. Increased Replicative Fitness Can Lead to Decreased Drug Sensitivity of Hepatitis C Virus

    Science.gov (United States)

    Sheldon, Julie; Beach, Nathan M.; Moreno, Elena; Gallego, Isabel; Piñeiro, David; Martínez-Salas, Encarnación; Gregori, Josep; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M.

    2014-01-01

    ABSTRACT Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV. IMPORTANCE Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness can confer a general drug resistance phenotype to the virus. The results exclude the possibility that genomes with drug resistance mutations are responsible for the observed phenotype. The fact that replicative fitness can be a determinant of multidrug resistance may explain why the virus is less sensitive to drug treatments in prolonged chronic HCV infections that favor increases in replicative fitness. PMID:25122776

  8. Comprehensive Drug Testing of Patient-derived Conditionally Reprogrammed Cells from Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Saeed, Khalid; Rahkama, Vesa; Eldfors, Samuli; Bychkov, Dmitry; Mpindi, John Patrick; Yadav, Bhagwan; Paavolainen, Lassi; Aittokallio, Tero; Heckman, Caroline; Wennerberg, Krister; Peehl, Donna M; Horvath, Peter; Mirtti, Tuomas; Rannikko, Antti; Kallioniemi, Olli; Östling, Päivi; Af Hällström, Taija M

    2017-03-01

    Technology development to enable the culture of human prostate cancer (PCa) progenitor cells is required for the identification of new, potentially curative therapies for PCa. We established and characterized patient-derived conditionally reprogrammed cells (CRCs) to assess their biological properties and to apply these to test the efficacies of drugs. CRCs were established from seven patient samples with disease ranging from primary PCa to advanced castration-resistant PCa (CRPC). The CRCs were characterized by genomic, transcriptomic, protein expression, and drug profiling. The phenotypic quantification of the CRCs was done based on immunostaining followed by image analysis with Advanced Cell Classifier using Random Forest supervised machine learning. Copy number aberrations (CNAs) were called from whole-exome sequencing and transcriptomics using in-house pipelines. Dose-response measurements were used to generate multiparameter drug sensitivity scores using R-statistical language. We generated six benign CRC cultures which all had an androgen receptor-negative, basal/transit-amplifying phenotype with few CNAs. In three-dimensional cell culture, these cells could re-express the androgen receptor. The CRCs from a CRPC patient (HUB.5) displayed multiple CNAs, many of which were shared with the parental tumor. We carried out high-throughput drug-response studies with 306 emerging and clinical cancer drugs. Using the benign CRCs as controls, we identified the Bcl-2 family inhibitor navitoclax as the most potent cancer-specific drug for the CRCs from a CRPC patient. Other drug efficacies included taxanes, mepacrine, and retinoids. Comprehensive cancer pharmacopeia-wide drug testing of CRCs from a CRPC patient highlighted both known and novel drug sensitivities in PCa, including navitoclax, which is currently being tested in clinical trials of CRPC. We describe an approach to generate patient-derived cancer cells from advanced prostate cancer and apply such cells to

  9. Sensitivity Tests for Cumulative Damage Function (CDF) for the PGSFR

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chiwoong; Ha, Kwiseok [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    A safety analysis including the design basis and beyond design basis events has been conducted using MARS-LMR. Previous safety limits were based on temperature and the duration time. However, the cumulative damage function (CDF) will be used as the safety limit to evaluate the fuel cladding integrity. Recently, a 4S reactor developed by Toshiba used the same approach for a safety analysis. Therefore, the development a CDF is necessary to evaluate the safety limit for the PGSFR safety analyses. The major keys in the CDF model are behavior of fuel and cladding. It is not easy to obtain a metallic fuel database for a CDF model including the cladding materials. Argonne National Laboratory (ANL) in the United States is the only major leading group for metallic fuel experiments. They conducted various experiments with various facilities and experimental reactors, for example, EBR-II, FFTF, and TREAT. In addition, they have recently been trying to extend their oxide fuel based a severe accident code, SAS4A/SASSYS, to a metallic fuel version using their metallic fuel database. In this study, the preliminary CDF model was supplemented in the MARS-LMR code. The major source was the SAS4A/SASSYS modules related to fuel and cladding transient behaviors.. In addition, a sensitivity test for some parameters in the CDF model was conducted to evaluate the capability of these models and to find the major parameter of fuel failure. The Cumulative Damage Function is a good indicator for a fuel failure. The major parameters for the CDF model are selected including cladding and fuel temperatures, initial pressure and volume in the gas plenum, clad thickness, and fission power in the fuel pin. The most sensitive parameter is the cladding temperature. Also, cladding thickness and gas pressure in the fuel pin are effective parameters on the CDF. During an actual transient, various parameter including sensitivity test parameters in this study will be changed simultaneously. This study can

  10. On the use of sensitivity tests in seismic tomography

    Science.gov (United States)

    Rawlinson, N.; Spakman, W.

    2016-05-01

    Sensitivity analysis with synthetic models is widely used in seismic tomography as a means for assessing the spatial resolution of solutions produced by, in most cases, linear or iterative nonlinear inversion schemes. The most common type of synthetic reconstruction test is the so-called checkerboard resolution test in which the synthetic model comprises an alternating pattern of higher and lower wave speed (or some other seismic property such as attenuation) in 2-D or 3-D. Although originally introduced for application to large inverse problems for which formal resolution and covariance could not be computed, these tests have achieved popularity, even when resolution and covariance can be computed, by virtue of being simple to implement and providing rapid and intuitive insight into the reliability of the recovered model. However, checkerboard tests have a number of potential drawbacks, including (1) only providing indirect evidence of quantitative measures of reliability such as resolution and uncertainty, (2) giving a potentially misleading impression of the range of scale-lengths that can be resolved, and (3) not giving a true picture of the structural distortion or smearing that can be caused by the data coverage. The widespread use of synthetic reconstruction tests in seismic tomography is likely to continue for some time yet, so it is important to implement best practice where possible. The goal of this paper is to develop the underlying theory and carry out a series of numerical experiments in order to establish best practice and identify some common pitfalls. Based on our findings, we recommend (1) the use of a discrete spike test involving a sparse distribution of spikes, rather than the use of the conventional tightly spaced checkerboard; (2) using data coverage (e.g. ray-path geometry) inherited from the model constrained by the observations (i.e. the same forward operator or matrix), rather than the data coverage obtained by solving the forward problem

  11. Olodaterol and vilanterol detection in sport drug testing.

    Science.gov (United States)

    Chundela, Zdenek; Große, Joachim

    2015-01-01

    The possibility of the detection of olodaterol and vilanterol, two novel β2 -agonists, in human urine for the purpose of sport drug testing was investigated. Compounds of interest were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) employing methods commonly used in the World Anti-Doping Agency (WADA) accredited laboratories. For both substances, the respective parent compound was found to be a suitable target analyte for monitoring therapeutic dose administration.

  12. Isolation, Identification and Drug Sensitivity Test of the Pathogenic Bacteria of Cow Subclinical Mastitis in Dalian Area%大连地区奶牛隐性乳房炎主要病原菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    郭海勇; 韩国华; 崔京春

    2011-01-01

    In order to clarify the major pathogenic bacteria and the incidence of cow subclinical mastitis in Dalian area,256 cows of the different lactation time were investigated from different areas of Dalian. The major pathogenic bacteria were isolated and identified from the milk samples of the subclinical mastitis in dairy cows, and the susceptibility to antibiotics for the major pathogenic bacteria was tested. The results showed that the positive rate of subclinical mastitis was 65. 63% and the mammary region positive rate of subclinical mastitis was 51. 95% in the tested cows; Staphylococcus aureus, Streptococcus and Escherichia coli were the major pathogenic bacteria causing cow subclinical mastitis,and the cases of cow subclinical mastitis caused with this three kinds of pathogenic bacteria were 83. 33 % ; the hypersensitive antibiotics to the major pathogenic bacteria of cow subclinical mastitis were screened by the drug sensitivity test in vitro, these hypersensitive antibiotics could efficiently treat cow subclinical mastitis in Dalian area.%为了明确引起大连地区奶牛隐性乳房炎的主要病原菌及其发病情况,对大连市不同地区的256头黑白花泌乳奶牛进行调查研究,对奶牛隐性乳房炎奶样进行病原菌的分离鉴定及药敏试验.结果表明,检出奶牛隐性乳房炎阳性率为65.63%、乳区阳性率为51.95%;病原菌以金黄色葡萄球菌(Staphylococcus aureus)、链球菌(Streptococcus)和大肠杆菌(Escherichia coli)为主,占检出细菌总数的83.33%;体外药敏试验筛选出了对主要病原菌高度敏感的药物,能有效地治疗奶牛隐性乳房炎.

  13. Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

  14. The Hug-up Test: A New, Sensitive Diagnostic Test for Supraspinatus Tears

    Institute of Scientific and Technical Information of China (English)

    Yu-Lei Liu; Ying-Fang Ao; Hui Yan; Guo-Qing Cui

    2016-01-01

    Background:The supraspinatus tendon is the most commonly affected tendon in rotator cufftears.Early detection ofa supraspinatus tear using an accurate physical examination is,therefore,important.However,the currently used physical tests for detecting supraspinatus tears are poor diagnostic indicators and involve a wide range of sensitivity and specificity values.Therefore,the aim of this study was to establish a new physical test for the diagnosis of supraspinatus tears and evaluate its accuracy in comparison with conventional tests.Methods:Between November 2012 and January 2014,200 consecutive patients undergoing shoulder arthroscopy were prospectively evaluated preoperatively.The hug-up test,empty can (EC) test,full can (FC) test,Neer impingement sign,and Hawkins-Kennedy impingement sign were used and compared statistically for their accuracy in terms of supraspinatus tears,with arthroscopic findings as the gold standard.Muscle strength was precisely quantified using an electronic digital tensiometer.Results:The prevalence of supraspinatus tears was 76.5%.The hug-up test demonstrated the highest sensitivity (94.1%),with a low negative likelihood ratio (NLR,0.08) and comparable specificity (76.6%) compared with the other four tests.The area under the receiver operating characteristic curve for the hug-up test was 0.854,with no statistical difference compared with the EC test (z =1.43 8,P =0.075) or the FC test (z =1.498,P =0.067).The hug-up test showed no statistical difference in terms of detecting different tear patterns according to the position (x2 =0.578,P =0.898) and size (Fisher's exact test,P > 0.999) compared with the arthroscopic examination.The interobserver reproducibility of the hug-up test was high,with a kappa coefficient of 0.823.Conclusions:The hug-up test can accurately detect supraspinatus tears with a high sensitivity,comparable specificity,and low NLR compared with the conventional clinical tests and could,therefore,improve the

  15. The Hug-up Test: A New, Sensitive Diagnostic Test for Supraspinatus Tears

    Directory of Open Access Journals (Sweden)

    Yu-Lei Liu

    2016-01-01

    Full Text Available Background: The supraspinatus tendon is the most commonly affected tendon in rotator cuff tears. Early detection of a supraspinatus tear using an accurate physical examination is, therefore, important. However, the currently used physical tests for detecting supraspinatus tears are poor diagnostic indicators and involve a wide range of sensitivity and specificity values. Therefore, the aim of this study was to establish a new physical test for the diagnosis of supraspinatus tears and evaluate its accuracy in comparison with conventional tests. Methods: Between November 2012 and January 2014, 200 consecutive patients undergoing shoulder arthroscopy were prospectively evaluated preoperatively. The hug-up test, empty can (EC test, full can (FC test, Neer impingement sign, and Hawkins-Kennedy impingement sign were used and compared statistically for their accuracy in terms of supraspinatus tears, with arthroscopic findings as the gold standard. Muscle strength was precisely quantified using an electronic digital tensiometer. Results: The prevalence of supraspinatus tears was 76.5%. The hug-up test demonstrated the highest sensitivity (94.1%, with a low negative likelihood ratio (NLR, 0.08 and comparable specificity (76.6% compared with the other four tests. The area under the receiver operating characteristic curve for the hug-up test was 0.854, with no statistical difference compared with the EC test (z = 1.438, P = 0.075 or the FC test (z = 1.498, P = 0.067. The hug-up test showed no statistical difference in terms of detecting different tear patterns according to the position (χ2 = 0.578, P = 0.898 and size (Fisher′s exact test, P > 0.999 compared with the arthroscopic examination. The interobserver reproducibility of the hug-up test was high, with a kappa coefficient of 0.823. Conclusions: The hug-up test can accurately detect supraspinatus tears with a high sensitivity, comparable specificity, and low NLR compared with the conventional

  16. Template synthesized chitosan nano test tubes for drug delivery applications

    Science.gov (United States)

    Perry, Jillian L. Moulton

    There is tremendous current interest in developing nanoscale drug delivery vehicles. Though intensive efforts have focused on developing spherical drug delivery vehicles, cylindrically shaped vehicles such as nanotubes offer many advantages. Typically, nanotubes can carry a larger inner payload than nanoparticles of the same diameter. Also, we can prepare nanotubes in templates whose geometries can be controlled, in turn allowing precise control over the length and diameter of the tubes. In addition, template synthesized nanotubes can be differentially functionalized on the inner and outer surfaces. Furthermore, templates that are closed on one end can be used to fabricate nano test tubes (closed on one end). The geometry of these nano test tubes allows them to be easily filled with a payload, the open end sealed with a nanoparticle to protect the payload from leaking out, and then the exterior of the tube can be functionalized with a targeting moiety. In an effort to develop such a system, we explored the fabrication of chitosan nano test tubes. Defect-free, chitosan nano test tubes of uniform size were synthesized within the pores of a nanoporous alumina template membrane. While the nano test tubes remained within the template membrane, their inner cavities were filled with a model payload. The payload was then trapped inside the nano test tubes by sealing the open ends of the tubes with latex nanoparticle caps. For proof-of-principle studies, imine linkages were used to attach the caps to the nano test tubes. To create a self-disassembling system, disulfide chemistry was used to covalently cap the nano test tubes. Once removed from the template, the exterior of the nano test tubes were modified with a targeting moiety, allowing them to be targeted to pathological sites. We have also shown that the chitosan nano test tubes are biodegradable by two systems: enzymatic cleavage by lysozymes and disulfide cleavage of the crosslinker by reducing environments

  17. The role of drug susceptibility testing in controlling drug resistant tuberculosis: Challenges and possibilities

    Directory of Open Access Journals (Sweden)

    Sven Hoffner

    2015-01-01

    Conclusions: Reliable and timely detection of drug-resistant TB is needed, which is best achieved with molecular assays. In this author's opinion, rapid detection of resistance to isoniazid should be included with rifampicin resistance examination. In MDR, timely detection of the XDR defining agents and PZA is urgently needed. Development and validation of such tests should be a priority, as well as establishing QMS for the implementation and routine use of molecular rapid diagnostics. Each country should develop national diagnostic algorithms for how, when and where rapid molecular assays should be used for early detection of drug-resistant TB.

  18. A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context

    Directory of Open Access Journals (Sweden)

    Stefano Gentili

    2016-01-01

    Full Text Available The reliability of DrugWipe 5A on site test for principal drugs of abuse (cannabis, amphetamines, cocaine, and opiates detection in oral fluid was assessed by comparing the on-site results with headspace solid-phase microextraction (HS-SPME gas chromatography-mass spectrometry (GC-MS analysis on samples extracted by the device collection pad. Oral fluid samples were collected at recreational settings (e.g., discos, pubs, and music bars of Rome metropolitan area. Eighty-three club goers underwent the on-site drug screening test with one device. Independently from the result obtained, a second device was used just to collect another oral fluid sample subsequently extracted and analyzed in the laboratory following HS-SPME procedure, gas chromatographic separation by a capillary column, and MS detection by electron impact ionization. DrugWipe 5A on-site test showed 54 samples (65.1% positive to one or more drugs of abuse, whereas 75 samples (90.4% tested positive for one or more substances following GC-MS assay. Comparing the obtained results, the device showed sensitivity, specificity, and accuracy around 80% for amphetamines class. Sensitivity (67 and 50% was obtained for cocaine and opiates, while both sensitivity and accuracy were unsuccessful (29 and 53%, resp. for cannabis, underlying the limitation of the device for this latter drug class.

  19. High Speed Pressure Sensitive Paint for Dynamic Testing

    Science.gov (United States)

    Pena, Carolina; Chism, Kyle; Hubner, Paul

    2016-11-01

    Pressure sensitive paint (PSP) allows engineers to obtain accurate, high-spatial-resolution measurements of pressure fields over a structure. The pressure is directly related to the luminescence emitted by the paint due to oxygen quenching. Fast PSP has a higher surface area due to its porosity compared to conventional PSP, which enables faster diffusion and measurements to be acquired three orders of magnitude faster than with conventional PSP. A fast time response is needed when testing vibrating structures due to fluid-structure interaction. The goal of this summer project was to set-up, test and analyze the pressure field of an impinging air jet on a vibrating cantilever beam using Fast PSP. Software routines were developed for the processing of the emission images, videos of a static beam coated with Fast PSP were acquired with the air jet on and off, and the intensities of these two cases were ratioed and calibrated to pressure. Going forward, unsteady pressures on a vibrating beam will be measured and presented. Eventually, the long-term goal is to integrate luminescent pressure and strain measurement techniques, simultaneously using Fast PSP and a luminescent photoelastic coating on vibrating structures. Funding from NSF REU site Grant EEC 1358991 is greatly appreciated.

  20. Local defect resonance for sensitive non-destructive testing

    Science.gov (United States)

    Adebahr, W.; Solodov, I.; Rahammer, M.; Gulnizkij, N.; Kreutzbruck, M.

    2016-02-01

    Ultrasonic wave-defect interaction is a background of ultrasound activated techniques for imaging and non-destructive testing (NDT) of materials and industrial components. The interaction, primarily, results in acoustic response of a defect which provides attenuation and scattering of ultrasound used as an indicator of defects in conventional ultrasonic NDT. The derivative ultrasonic-induced effects include e.g. nonlinear, thermal, acousto-optic, etc. responses also applied for NDT and defect imaging. These secondary effects are normally relatively inefficient so that the corresponding NDT techniques require an elevated acoustic power and stand out from conventional ultrasonic NDT counterparts for their specific instrumentation particularly adapted to high-power ultrasonic. In this paper, a consistent way to enhance ultrasonic, optical and thermal defect responses and thus to reduce an ultrasonic power required is suggested by using selective ultrasonic activation of defects based on the concept of local defect resonance (LDR). A strong increase in vibration amplitude at LDR enables to reliably detect and visualize the defect as soon as the driving ultrasonic frequency is matched to the LDR frequency. This also provides a high frequency selectivity of the LDR-based imaging, i.e. an opportunity of detecting a certain defect among a multitude of other defects in material. Some examples are shown how to use LDR in non-destructive testing techniques, like vibrometry, ultrasonic thermography and shearography in order to enhance the sensitivity of defect visualization.

  1. Role of pressure-sensitive adhesives in transdermal drug delivery systems.

    Science.gov (United States)

    Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

    2016-01-01

    Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

  2. Workplace drug testing in Italy: findings about second-stage testing.

    Science.gov (United States)

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; San Bartolomeo, Paolo; Groppi, Angelo

    2015-03-01

    Workplace Drug Testing (WDT) in Italy includes two levels of monitoring: a first stage concerning drug testing on urine samples and a second involving both urine and hair analysis. The second stage is performed only on workers who tested positive at the first level. We analyzed urine and hair specimens from 120 workers undergoing second-level testing between 2009 and 2012. Eighty percent of them had tested positive for cannabinoids during the first level analysis, and 15.8% for cocaine. Both urine and hair samples were analyzed in order to find the following drugs of abuse: amphetamines, buprenorphine, cannabinoids, cocaine, ecstasy, methadone, and opiates. Urine analyses were performed by immunological screening (EMIT); urine confirmatory tests and hair analyses were performed by gas chromatography-mass spectrometry (GC-MS). As regards second-stage testing on urine samples, 71.2% of workers were always negative, whereas 23.9% tested positive at least once for cannabinoids and 2.5% for cocaine. Hair analyses produced surprising results: 61.9% of hair samples tested negative, only 6.2% tested positive for cannabinoids, whereas 28.8% tested positive for cocaine. These findings confirm that second-level surveillance of WDT, which includes hair analysis, is very effective because it highlights drug intake - sometimes heavy - that cannot be revealed only through urine analyses. The employees for whom drug addiction is proved can begin rehabilitation, while keeping their job. Eventually, our results confirmed the widespread and undeclared use of cocaine in Italy. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Functionality test for drug safety alerting in computerized physician order entry systems.

    Science.gov (United States)

    van der Sijs, Heleen; Bouamar, Rachida; van Gelder, Teun; Aarts, Jos; Berg, Marc; Vulto, Arnold

    2010-04-01

    To evaluate the functionality of drug safety alerting in hospital computerized physician order entry (CPOE) systems by a newly developed comprehensive test. Comparative evaluation of drug safety alerting quality in 6 different CPOEs used in Dutch hospitals, by means of 29 test items for sensitivity and 19 for specificity in offices of CPOE system vendors. Sensitivity and specificity were calculated for the complete test, and for the categories "within-order checks", "patient-specific checks", and "checks related to laboratory data and new patient conditions". Qualitative interviews with 16 hospital pharmacists evaluating missing functionality and corresponding pharmacy checks. Sensitivity ranged from 0.38 to 0.79 and specificity from 0.11 to 0.84. The systems achieved the same ranking for sensitivity as for specificity. Within-order checks and patient-specific checks were present in all systems; alert generation or suppression due to laboratory data and new patient conditions was largely absent. Hospital pharmacists unanimously rated checks on contra-indications (absent in 2 CPOEs) and dose regimens less than once a day (absent in 4 CPOEs) as important. Pharmacists' opinions were more divergent for other test items. A variety of pharmacy checks were used, and clinical rules developed, to address missing functionality. Our test revealed widely varying functionality and appeared to be highly discriminative. Basic clinical decision support was partly absent in two CPOEs. Hospital pharmacists did not rate all test items as important and tried to accommodate the lacking functionality by performing additional checks and developing clinical rules. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Effectiveness of saliva and fingerprints as alternative specimens to urine and blood in forensic drug testing.

    Science.gov (United States)

    Kuwayama, Kenji; Miyaguchi, Hajime; Yamamuro, Tadashi; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

    2016-07-01

    In forensic drug testing, it is important to immediately take biological specimens from suspects and victims to prove their drug intake. We evaluated the effectiveness of saliva and fingerprints as alternative specimens to urine and blood in terms of ease of sampling, drug detection sensitivity, and drug detection periods for each specimen type. After four commercially available pharmaceutical products were administered to healthy subjects, each in a single dose, their urine, blood, saliva, and fingerprints were taken at predetermined sampling times over approximately four weeks. Fourteen analytes (the administered drugs and their main metabolites) were extracted from each specimen using simple pretreatments, such as dilution and deproteinization, and were analyzed using liquid chromatography/mass spectrometry (LC/MS). Most of the analytes were detected in saliva and fingerprints, as well as in urine and blood. The time-courses of drug concentrations were similar between urine and fingerprints, and between blood and saliva. Compared to the other compounds, the acidic compounds, for example ibuprofen, acetylsalicylic acid, were more difficult to detect in all specimens. Acetaminophen, dihydrocodeine, and methylephedrine were detected in fingerprints at later sampling times than in urine. However, a relationship between the drug structures and their detection periods in each specimen was not found. Saliva and fingerprints could be easily sampled on site without using special techniques or facilities. In addition, fingerprints could be immediately analyzed after simple and rapid treatment. In cases where it would be difficult to immediately obtain urine and blood, saliva and fingerprints could be effective alternative specimens for drug testing. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Sensitivity study on hydraulic well testing inversion using simulated annealing

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Shinsuke; Najita, J.; Karasaki, Kenzi

    1997-11-01

    For environmental remediation, management of nuclear waste disposal, or geothermal reservoir engineering, it is very important to evaluate the permeabilities, spacing, and sizes of the subsurface fractures which control ground water flow. Cluster variable aperture (CVA) simulated annealing has been used as an inversion technique to construct fluid flow models of fractured formations based on transient pressure data from hydraulic tests. A two-dimensional fracture network system is represented as a filled regular lattice of fracture elements. The algorithm iteratively changes an aperture of cluster of fracture elements, which are chosen randomly from a list of discrete apertures, to improve the match to observed pressure transients. The size of the clusters is held constant throughout the iterations. Sensitivity studies using simple fracture models with eight wells show that, in general, it is necessary to conduct interference tests using at least three different wells as pumping well in order to reconstruct the fracture network with a transmissivity contrast of one order of magnitude, particularly when the cluster size is not known a priori. Because hydraulic inversion is inherently non-unique, it is important to utilize additional information. The authors investigated the relationship between the scale of heterogeneity and the optimum cluster size (and its shape) to enhance the reliability and convergence of the inversion. It appears that the cluster size corresponding to about 20--40 % of the practical range of the spatial correlation is optimal. Inversion results of the Raymond test site data are also presented and the practical range of spatial correlation is evaluated to be about 5--10 m from the optimal cluster size in the inversion.

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

    Science.gov (United States)

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

    2017-03-01

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

  7. Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems.

    Science.gov (United States)

    Jelezova, Ivelina; Drakalska, Elena; Momekova, Denitsa; Shalimova, Natalia; Momekov, Georgi; Konstantinov, Spiro; Rangelov, Stanislav; Pispas, Stergios

    2015-10-12

    Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells.

  8. Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs.

    Science.gov (United States)

    Safaei, Roohangiz; Howell, Stephen B

    2005-01-01

    Recent studies have demonstrated that the major Cu influx transporter CTR1 regulates tumor cell uptake of cisplatin (DDP), carboplatin (CBDCA) and oxaliplatin (L-OHP), and that the two Cu efflux transporters ATP7A and ATP7B regulate the efflux of these drugs. Evidence for the concept that these platinum (Pt) drugs enter cells and are distributed to various subcellular compartments via transporters that have evolved to manage Cu homeostasis includes the demonstration of: (1) bidirectional cross-resistance between cells selected for resistance to either the Pt drugs or Cu; (2) parallel changes in the transport of Pt and Cu drugs in resistant cells; (3) altered cytotoxic sensitivity and Pt drug accumulation in cells transfected with Cu transporters; and (4) altered expression of Cu transporters in Pt drug-resistant tumors. Appreciation of the role of the Cu transporters in the development of resistance to DDP, CBDCA, and L-OHP offers novel insights into strategies for preventing or reversing resistance to this very important family of anticancer drugs.

  9. 49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

    Science.gov (United States)

    2010-10-01

    ... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

  10. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-06-15

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

  11. Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs.

    Science.gov (United States)

    Hsu, Chia-Chi; Wu, Ling-Chia; Hsia, Cheng-Yuan; Yin, Pen-Hui; Chi, Chin-Wen; Yeh, Tien-Shun; Lee, Hsin-Chen

    2015-09-01

    Human hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide particularly in Asia. Deregulation of cellular energetics was recently included as one of the cancer hallmarks. Compounds that target the mitochondria in cancer cells were proposed to have therapeutic potential. Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients. However, whether alteration of energy metabolism is involved in regulating the sensitivity of HCC to biguanide drugs is still unclear. In the present study, we treated four HCC cell lines with mitochondrial inhibitors (rotenone and oligomycin) and biguanide drugs (metformin and phenformin), and found that the HCC cells which had a higher mitochondrial respiration rate were more sensitive to these treatments; whereas the HCC cells which exhibited higher glycolysis were more resistant. When glucose was replaced by galactose in the medium, the altered energy metabolism from glycolysis to mitochondrial respiration in the HCC cells enhanced the cellular sensitivity to mitochondrial inhibitors and biguanides. The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides. In conclusion, our results suggest that increased mitochondrial oxidative metabolism upregulates the sensitivity of HCC to biguanide drugs. Enhancing the mitochondrial oxidative metabolism in combination with biguanide drugs may be a therapeutic strategy for HCC.

  12. Thermo-sensitive complex micelles from sodium alginate-graft-poly(N-isopropylacrylamide) for drug release.

    Science.gov (United States)

    Yu, Nana; Li, Guiying; Gao, Yurong; Jiang, Hua; Tao, Qian

    2016-05-01

    Polymer micelles with environmentally sensitive properties have potential applications in biomedicine. In this paper, thermo-sensitive complex micelles assembled from biocompatible graft copolymers sodium alginate-graft-poly(N-isopropylacrylamide) (SA-g-PNIPAM) and divalent metal ions were prepared for controlled drug release. The polymer micelles had core-corona structure, which was constituted by metal ions (Ba(2+), Zn(2+), Co(2+)) cross-linked sodium alginate as the core and thermo-sensitive PNIPAM chains as the corona. Formation of polymer micelles was determined by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The polymer micelles were observed as regular spheres with good polydispersity and excellent performance on drug encapsulation and release ability. The cumulative release of 5-fluorouracil (5-FU) from micelles was controlled by pH, ionic strength or temperature of surroundings. The superior properties of sensitive polymer micelles induced by metal ions are expected to be utilized in controlled drug delivery systems.

  13. Application of drug testing using exhaled breath for compliance monitoring of drug addicts in treatment.

    Science.gov (United States)

    Carlsson, Sten; Olsson, Robert; Lindkvist, Irene; Beck, Olof

    2015-04-01

    Exhaled breath has recently been identified as a possible matrix for drug testing. This study explored the potential of this new method for compliance monitoring of patients being treated for dependence disorders. Outpatients in treatment programs were recruited for this study. Urine was collected as part of clinical routine and a breath sample was collected in parallel together with a questionnaire about their views of the testing procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis, cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical screening and mass spectrometry confirmation. The exhaled breath was collected using the SensAbues device and analyzed by mass spectrometry for amphetamine, methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine, benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6-acetylmorphine. A total of 122 cases with parallel urine and breath samples were collected; 34 of these were negative both in urine and breath. Out of 88 cases with positive urine samples 51 (58%) were also positive in breath. Among the patients on methadone treatment, all were positive for methadone in urine and 83% were positive in breath. Among patients in treatment with buprenorphine, 92% were positive in urine and among those 80% were also positive in breath. The questionnaire response documented that in general, patients accepted drug testing well and that the breath sampling procedure was preferred. Compliance testing for the intake of prescribed and unprescribed drugs among patients in treatment for dependence disorders using the exhaled breath sampling technique is a viable method and deserves future attention.

  14. 陕西某奶牛场隐性乳房炎病原菌分离鉴定及药敏试验%Isolation and Identification of Subclinical Mastitis Pathogens and Drug Sensitivity Tests in A Dairy Cow Farm of Shanxi Province

    Institute of Scientific and Technical Information of China (English)

    高海慧; 任敏; 郭抗抗; 张彦明

    2014-01-01

    To understand the incidence of a recessive mastitis of dairy cows,using LMT to detect subclinical mastitis on 165 clinical healthy cows,48 milk samples with subclinical mastitis were detected,and the pathogens isolated,biochemical identified,and drug sensitivities were tested.The results showed that positeve rate of subclinical mastitis is 43.64%,the positive rate of udder quarter is 24.46%,all of mam-mary areas could catch the disease,the incidence of dairy subclinical mastitis closely connected with parity and age.One handred and seven strains bacteria were isolated,the main pathogenic bacteria are Staphylo-coccus aureus ,Streptococcus and E.coli.Among the 107 isolated pathogens,there were 32 strains of Staphylococcus aureus (29.91%),15 strains of Streptococcus (14.02%),14 strains of Escherichia coli (13.08%).Three main pathogens were sensitive to ofloxacin,amikacin,ciprofloxacin,and resistant to streptomycin,penicillin,amoxicillin and Ampicillin.Dairy subclinical mastitis was on the rise with the in-crease of parity and age .Ofloxacin,amikacin,ciprofloxacin could be selected as the candidate drugs for treating the dairy subclinical mastitis in the farm.%为了解某场奶牛隐性乳房炎发生情况,应用 LMT 法对该奶牛场的165头临床健康奶牛进行隐性乳房炎检测,采集阳性乳样48份进行病原菌的分离鉴定,并对其主要病原菌进行了药敏试验。结果表明,该奶牛场奶牛隐性乳房炎阳性率为43.64%,乳区阳性率为24.46%,每个乳区均可发病,奶牛隐性乳房炎发病率与胎次和年龄有密切的关系,随着胎次和年龄的增加,奶牛隐性乳房炎发病率呈上升趋势;从阳性乳样中分离出11种107株细菌,主要病原菌为金黄色葡萄球菌、链球菌和大肠埃希菌。其中,金黄色葡萄球菌32株,占29.91%;链球菌15株,占14.02%;大肠埃希菌14株,占13.08%。3种主要病原菌对氧氟沙

  15. Isolation,Identification and Drug Sensitivity Tests of Main Pathogenic Bacteria Causing Cow Endometritis in Dairy Cow Farms of Ningxia%宁夏地区奶牛子宫内膜炎主要病原菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    赵清梅; 余永涛; 任贤

    2015-01-01

    为调查宁夏6个规模化牛场奶牛子宫内膜炎主要致病菌的种类及其耐药情况,采集78头患子宫内膜炎奶牛的子宫分泌物,分离培养细菌,根据各分离菌株的生化反应和16 S rDNA 序列遗传进化分析结果,对致病菌分类鉴定,并对其进行抗生素耐药性分析。结果表明,大肠埃希菌检出率为55.56%,金黄色葡萄球菌检出率为35.90%,其他菌株检出率为8.54%,单一菌株感染患牛占42.31%,混合菌株感染占52.56%。大肠埃希菌和金色葡萄球菌对青霉素 G、氨苄西林、四环素、复方新诺明、链霉素、卡拉霉素耐药性较强(50%~100%),对万古霉素、头孢西丁、头孢噻肟较为敏感(耐药率小于20%)。宁夏6个规模化牛场奶牛子宫内膜炎主要致病菌为大肠埃希菌和金黄色葡萄球菌,且以混合感染为主。该类病原对青霉素类、四环素类、氨基糖甙类和磺胺类抗生素耐药性较强,对万古霉素、头孢类较敏感。%To evaluate the species and drug resistance of main pathogenic bacteria causing cow endometri-tis,this experiment was performed to isolate bacteria from the excretion of uteruses of 78 affected cows in six large-scale dairy farms located in Ningxia.The main isolates were classified according to the results of biochemical identification and phylogenetic analysis based on 16 S rDNA sequences.The drug sensitivity tests of the main isolates were conducted.The results indicated that 55.56 percent of pathogens are Esche-richia coli and 35.90 percent of pathogens are Staphylococcus aureus .Other species of pathogens accoun-ted for 8.54 percent of all isolates.42.31 percent of all affected cows infected with single pathogen.It ac-counted for 52.56 percent of affected cows that infected with mixed pathogens.The isolated E.coli and S. aureus were resistant to the majority of antibacterial agents such as penicillin G

  16. Investigation of drugs responsible for perioperative anaphylactic reactions using cellular allergen stimulation test

    Institute of Scientific and Technical Information of China (English)

    Xin Xin; Zou Yi; Xing Lijiao; Yin Jia; Gu Jianqing; Wang Zixi; Huang Yuguang

    2014-01-01

    Background Anaphylactic reactions during anesthesia and operation are common and life threatening.Follow-up investigation is necessary for avoiding potential re-exposure of the patients to the offending drugs.The purpose of this study was to assess cellular allergen stimulation test (CAST) as a diagnostic instrument in immunoglobulin E (IgE)-and non-lgE-mediated anaphylactic reactions.Methods This study included 25 patients who developed perioperative anaphylactic reactions and 10 subjects that tolerated anesthetics and other drugs during perioperative period from September 2009 to October 2013 in Peking Union Medical College Hospital.We performed skin tests and flow cytometric analysis of basophil activation-based CAST in all subjects.Results Of the 25 patients,17 had IgE-mediated anaphylactic reactions (causative agent identified by skin tests) and 8 had non-lgE-mediated anaphylactic reactions (negative skin tests).CAST showed a sensitivity of 42.9%,specificity of 90%,and negative predictive value of 80.6% for neuromuscular blocking agents.Conclusions CAST may be useful for the diagnosis of anaphylactic reactions during perioperative period.Our findings call for further investigation to increase the sensitivity of the test.

  17. Animal models for testing anti-prion drugs.

    Science.gov (United States)

    Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

    2013-01-01

    Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-27

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

  19. The Influence of Drug Testing and Benefit-Based Distribution of Opioid Substitution Therapy on Drug Abstinence.

    Science.gov (United States)

    Gabrovec, Branko

    2015-01-01

    The objective of our research was to discover whether the new approach to urine drug testing has a positive effect on users' abstinence, users' treatment, and their cooperation, while remaining user-friendly, and whether this approach is more cost-effective. The centers are focused on providing high-quality treatment within a cost-efficient program. In this study, we focus on the influence of drug testing and benefit-based distribution of opioid substitution therapy (BBDOST) on drug abstinence. The purpose of this study was to find any possible positive effect of modified distribution of the therapy and illicit drug testing on the number of users who are abstinent from illicit drugs and users who are not abstinent from illicit drugs as well as the users' opinion on BBDOST and testing. We are also interested in a difference in abstinence rates between those on BBDOST and those not receiving BBDOST. In 2010, the method of drug testing at the center was changed (less frequent and random drug testing) to enable its users faster access to BBDOST (take-home therapy). It was found that the number of drug-abstinent program participants has increased from initial 44.5% (2010) to 54.1% (2014). According to the program participants, the new method allows them to achieve and maintain abstinence from drugs more easily. In addition, they are also satisfied with the modified way of drug testing. This opinion does not change with age, gender, and acquired benefits.

  20. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy.

    Directory of Open Access Journals (Sweden)

    Adam Szulkin

    Full Text Available BACKGROUND: Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit. MATERIALS AND METHODS: We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers. RESULTS: As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect. CONCLUSIONS: The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma.

  1. Assessment of wavefront aberration and contrast sensitivity test as evaluation of postoperative visual quality

    OpenAIRE

    Min Gong; Yi Liu; Bi Yang

    2013-01-01

    Effective methods of evaluating postoperative visual quality include wavefront aberration and contrast sensitivity test. This article provides a review of the concepts and clinical applications as well as their interactions of wavefront aberration and contrast sensitivity test.This article also provides a comprehensive assessment of the effectiveness of wavefront aberration and contrast sensitivity test as evaluation tools of postoperative visual quality.

  2. [Annual review of serotypes of E. coli isolated from various lesions in poultry and their sensitivity to drugs in vitro (author's transl)].

    Science.gov (United States)

    Goren, E

    1976-05-15

    550 Strains of E. coli, isolated from poultry, were typed. In addition, their sensitivity to various drugs was tested. A wide variety of serotypes was found to be present. Approximately 50% of the isolated strains of E. coli were found to be resistant to the tetracyclines, streptomycin and sulphafurazole. Chloramphenicol, neomycin and furazolidone usually were effective.

  3. Pressure-Sensitive Paints Advance Rotorcraft Design Testing

    Science.gov (United States)

    2013-01-01

    The rotors of certain helicopters can spin at speeds as high as 500 revolutions per minute. As the blades slice through the air, they flex, moving into the wind and back out, experiencing pressure changes on the order of thousands of times a second and even higher. All of this makes acquiring a true understanding of rotorcraft aerodynamics a difficult task. A traditional means of acquiring aerodynamic data is to conduct wind tunnel tests using a vehicle model outfitted with pressure taps and other sensors. These sensors add significant costs to wind tunnel testing while only providing measurements at discrete locations on the model's surface. In addition, standard sensor solutions do not work for pulling data from a rotor in motion. "Typical static pressure instrumentation can't handle that," explains Neal Watkins, electronics engineer in Langley Research Center s Advanced Sensing and Optical Measurement Branch. "There are dynamic pressure taps, but your costs go up by a factor of five to ten if you use those. In addition, recovery of the pressure tap readings is accomplished through slip rings, which allow only a limited amount of sensors and can require significant maintenance throughout a typical rotor test." One alternative to sensor-based wind tunnel testing is pressure sensitive paint (PSP). A coating of a specialized paint containing luminescent material is applied to the model. When exposed to an LED or laser light source, the material glows. The glowing material tends to be reactive to oxygen, explains Watkins, which causes the glow to diminish. The more oxygen that is present (or the more air present, since oxygen exists in a fixed proportion in air), the less the painted surface glows. Imaged with a camera, the areas experiencing greater air pressure show up darker than areas of less pressure. "The paint allows for a global pressure map as opposed to specific points," says Watkins. With PSP, each pixel recorded by the camera becomes an optical pressure

  4. A Cytoplasmic Form of Gaussia luciferase Provides a Highly Sensitive Test for Cytotoxicity

    Science.gov (United States)

    Tsuji, Saori; Ohbayashi, Tetsuya; Yamakage, Kohji; Oshimura, Mitsuo; Tada, Masako

    2016-01-01

    The elimination of unfavorable chemicals from our environment and commercial products requires a sensitive and high-throughput in vitro assay system for drug-induced hepatotoxicity. Some previous methods for evaluating hepatotoxicity measure the amounts of cytoplasmic enzymes secreted from damaged cells into the peripheral blood or culture medium. However, most of these enzymes are proteolytically digested in the extracellular milieu, dramatically reducing the sensitivity and reliability of such assays. Other methods measure the decrease in cell viability following exposure to a compound, but such endpoint assays are often confounded by proliferation of surviving cells that replace dead or damaged cells. In this study, with the goal of preventing false-negative diagnoses, we developed a sensitive luminometric cytotoxicity test using a stable form of luciferase. Specifically, we converted Gaussia luciferase (G-Luc) from an actively secreted form to a cytoplasmic form by adding an ER-retention signal composed of the four amino acids KDEL. The bioluminescent signal was >30-fold higher in transgenic HepG2 human hepatoblastoma cells expressing G-Luc+KDEL than in cells expressing wild-type G-Luc. Moreover, G-Luc+KDEL secreted from damaged cells was stable in culture medium after 24 hr at 37°C. We evaluated the accuracy of our cytotoxicity test by subjecting identical samples obtained from chemically treated transgenic HepG2 cells to the G-Luc+KDEL assay and luminometric analyses based on secretion of endogenous adenylate kinase or cellular ATP level. Time-dependent accumulation of G-Luc+KDEL in the medium increased the sensitivity of our assay above those of existing tests. Our findings demonstrate that strong and stable luminescence of G-Luc+KDEL in human hepatocyte-like cells, which have high levels of metabolic activity, make it suitable for use in a high-throughput screening system for monitoring time-dependent cytotoxicity in a limited number of cells. PMID

  5. Optimization and validation of CEDIA drugs of abuse immunoassay tests in serum on Hitachi 912.

    Science.gov (United States)

    Kirschbaum, Katrin M; Musshoff, Frank; Schmithausen, Ricarda; Stockhausen, Sarah; Madea, Burkhard

    2011-10-10

    Due to sensitive limits of detection of chromatographic methods and low limit values regarding the screening of drugs under the terms of impairment in safe driving (§ 24a StVG, Street Traffic Law in Germany), preliminary immunoassay (IA) tests should be able to detect also low concentrations of legal and illegal drugs in serum in forensic cases. False-negatives should be avoided, the rate of false-positive samples should be low due to cost and time. An optimization of IA cutoff values and a validation of the assay is required for each laboratory. In a retrospective study results for serum samples containing amphetamine, methylenedioxy derivatives, cannabinoids, benzodiazepines, cocaine (metabolites), methadone and opiates obtained with CEDIA drugs of abuse reagents on a Hitachi 912 autoanalyzer were compared with quantitative results of chromatographic methods (gas or liquid chromatography coupled with mass spectrometry (GC/MS or LC/MS)). Firstly sensitivity, specificity, positive and negative predictive values and overall misclassification rates were evaluated by contingency tables and compared to ROC-analyses and Youden-Indices. Secondly ideal cutoffs were statistically calculated on the basis of sensitivity and specificity as decisive statistical criteria with focus on a high sensitivity (low rates of false-negatives), i.e. using the Youden-Index. Immunoassay (IA) and confirmatory results were available for 3014 blood samples. Sensitivity was 90% or more for nearly all analytes: amphetamines (IA cutoff 9.5 ng/ml), methylenedioxy derivatives (IA cutoff 5.5 ng/ml), cannabinoids (IA cutoff 14.5 ng/ml), benzodiazepines (IA cutoff >0 ng/ml). Test of opiates showed a sensitivity of 86% for a IA cutoff value of >0 ng/ml. Values for specificity ranged between 33% (methadone, IA cutoff 10 ng/ml) and 90% (cocaine, IA cutoff 20 ng/ml). Lower cutoff values as recommended by ROC analyses were chosen for most tests to decrease the rate of false-negatives. Analyses enabled

  6. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.

    Science.gov (United States)

    Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A; Kim, Sungjoon; Wilson, Christopher J; Lehár, Joseph; Kryukov, Gregory V; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F; Monahan, John E; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H; Cheng, Jill; Yu, Guoying K; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P; Gabriel, Stacey B; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E; Weber, Barbara L; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L; Meyerson, Matthew; Golub, Todd R; Morrissey, Michael P; Sellers, William R; Schlegel, Robert; Garraway, Levi A

    2012-03-28

    The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.

  7. Systematic identification of genomic markers of drug sensitivity in cancer cells.

    Science.gov (United States)

    Garnett, Mathew J; Edelman, Elena J; Heidorn, Sonja J; Greenman, Chris D; Dastur, Anahita; Lau, King Wai; Greninger, Patricia; Thompson, I Richard; Luo, Xi; Soares, Jorge; Liu, Qingsong; Iorio, Francesco; Surdez, Didier; Chen, Li; Milano, Randy J; Bignell, Graham R; Tam, Ah T; Davies, Helen; Stevenson, Jesse A; Barthorpe, Syd; Lutz, Stephen R; Kogera, Fiona; Lawrence, Karl; McLaren-Douglas, Anne; Mitropoulos, Xeni; Mironenko, Tatiana; Thi, Helen; Richardson, Laura; Zhou, Wenjun; Jewitt, Frances; Zhang, Tinghu; O'Brien, Patrick; Boisvert, Jessica L; Price, Stacey; Hur, Wooyoung; Yang, Wanjuan; Deng, Xianming; Butler, Adam; Choi, Hwan Geun; Chang, Jae Won; Baselga, Jose; Stamenkovic, Ivan; Engelman, Jeffrey A; Sharma, Sreenath V; Delattre, Olivier; Saez-Rodriguez, Julio; Gray, Nathanael S; Settleman, Jeffrey; Futreal, P Andrew; Haber, Daniel A; Stratton, Michael R; Ramaswamy, Sridhar; McDermott, Ultan; Benes, Cyril H

    2012-03-28

    Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

  8. Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system.

    Science.gov (United States)

    Cetin, Emel Oyku; Gundogdu, Evren; Baspinar, Yücel; Karasulu, Ercument; Kirilmaz, Levent

    2013-12-01

    The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system.

  9. Enzastaurin inhibits tumours sensitive and resistant to anti-EGFR drugs

    Science.gov (United States)

    Gelardi, T; Caputo, R; Damiano, V; Daniele, G; Pepe, S; Ciardiello, F; Lahn, M; Bianco, R; Tortora, G

    2008-01-01

    We investigated the antitumour effect and ability to overcome the resistance to anti-EGFR drugs of enzastaurin, an inhibitor of VEGFR-dependent PKCβ signalling. Enzastaurin was evaluated alone and in combination with the EGFR inhibitor gefitinib, on growth and signalling protein expression in human cancer cells sensitive and resistant to anti-EGFR drugs, both in vitro and in nude mice. We demonstrated the marked inhibitory activity of enzastaurin against GEO colon and PC3 prostate cancer cells and their gefitinib-resistant counterparts GEO-GR and PC3-GR, accompanied by inhibition of pAkt and its effector pp70S6K, pGSK3β and VEGF expression and secretion. Moreover, enzastaurin showed a cooperative effect with gefitinib in parental and in gefitinib-resistant cells. Remarkably, these results were confirmed in vivo, where enzastaurin showed antitumour activity and cooperativity with gefitinib in mice grafted with GEO and GEO-GR tumours, incrementing their median survival and inhibiting the aforesaid protein expression and secretion in tumour specimens. In conclusion, enzastaurin by interfering with signalling proteins implicated in EGFR drug resistance markedly cooperates with gefitinib in sensitive and gefitinib-resistant tumours, thus overcoming and reverting such resistance and providing a rational basis for its development in patients resistant to anti-EGFR drugs. PMID:18665191

  10. Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

    Science.gov (United States)

    Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

    2013-03-01

    New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

  11. Galactosylated cellulosic sponge for multi-well drug safety testing.

    Science.gov (United States)

    Nugraha, Bramasta; Hong, Xin; Mo, Xuejun; Tan, Looling; Zhang, Wenxia; Chan, Po-Mak; Kang, Chiang Huen; Wang, Yan; Beng, Lu Thong; Sun, Wanxin; Choudhury, Deepak; Robens, Jeffrey M; McMillian, Michael; Silva, Jose; Dallas, Shannon; Tan, Choon-Hong; Yue, Zhilian; Yu, Hanry

    2011-10-01

    Hepatocyte spheroids can maintain mature differentiated functions, but collide to form bulkier structures when in extended culture. When the spheroid diameter exceeds 200 μm, cells in the inner core experience hypoxia and limited access to nutrients and drugs. Here we report the development of a thin galactosylated cellulosic sponge to culture hepatocytes in multi-well plates as 3D spheroids, and constrain them within a macroporous scaffold network to maintain spheroid size and prevent detachment. The hydrogel-based soft sponge conjugated with galactose provided suitable mechanical and chemical cues to support rapid formation of hepatocyte spheroids with a mature hepatocyte phenotype. The spheroids tethered in the sponge showed excellent maintenance of 3D cell morphology, cell-cell interaction, polarity, metabolic and transporter function and/or expression. For example, cytochrome P450 (CYP1A2, CYP2B2 and CYP3A2) activities were significantly elevated in spheroids exposed to β-naphthoflavone, phenobarbital, or pregnenolone-16α-carbonitrile, respectively. The sponge also exhibits minimal drug absorption compared to other commercially available scaffolds. As the cell seeding and culture protocols are similar to various high-throughput 2D cell-based assays, this platform is readily scalable and provides an alternative to current hepatocyte platforms used in drug safety testing applications.

  12. 宁夏地区奶牛隐性乳房炎主要病原菌分离鉴定及药敏试验%Isolation and Identiifcation of Subclinical Mastitis Pathogens and Drug Sensitivity Tests in Dairy Cows in Ningxia Autonomous Region

    Institute of Scientific and Technical Information of China (English)

    吴亚文; 张学军; 王磊; 李志红; 杨佳冰; 张玉玲; 李莉娟; 安泓霏; 王玉梅; 王晓亮; 张和平

    2015-01-01

    [目的]了解宁夏地区奶牛隐性乳房炎主要病原菌流行情况及主要病原菌的耐药特征。[方法]采集宁夏地区5个规模化奶牛养殖场乳样共计461份,分离培养后,应用全自动细菌鉴定仪进行鉴定并选择主要致病菌进行药敏试验。[结果]隐性乳房炎阳性检出率平均为65.3%(301/461);分离到金黄色葡萄球菌22株、无乳链球菌5株、大肠杆菌10株。这些细菌对阿米卡星、头孢噻肟等药物敏感,对青霉素与环丙沙星耐药。[结论]宁夏地区奶牛隐性乳房炎的阳性率较高,主要病原菌对阿米卡星、头孢噻肟等药物敏感。%[Objective] To clarify the species and distribution of cow sub-mastitis pathogens in Ningxia Hui Autonomous Region and identify the antimicrobial resistance of the main pathogens. [Method] 461 milk samples were collected from dairy cows with subclinical mastitis in five dairy farms for isolation and identification of pathogenic bacteria. Identification and drug sensitivity tests of the prominent pathogens were conducted by means of automatic bacteria identification equipment. [Result] The results indicated that the positive rate in the sub-mastitis cows was 65.3%(301/461). Three pathogenic bacteria were isolated,including 22 Staphylococcus aureus strains,5 Streptococcus agalactiae strains and 10 Escherichia coli strains. These bacteria were resistant to penicillin and ciprofloxacin,but all showed susceptibility to cefotaxime and amikacin. [Conclusion] Pathogens isolated and identified in this experiment were susceptible to cefotaxime and amikacin.

  13. Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines

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    Chunyu YANG

    2009-10-01

    Full Text Available Background and objective Screening of small-cell lung cancer (SCLC and non-small cell lung cancer (NSCLC cell lines with gemcitabine hydrochloride (GEM and cisplatin (CDDP related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r≥0.632, P < 0.05 with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4. Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules, Cathepsin B (Organization protease B and TIMP1 (Growth factor; the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.

  14. NOVEL pH-SENSITIVE DRUG DELIVERY SYSTEM BASED ON NATURAL POLYSACCHARIDE FOR DOXORUBICIN RELEASE

    Institute of Scientific and Technical Information of China (English)

    Dian-xiang Lu; Xian-tao Wen; Jie Liang; Xing-dong Zhang; Zhong-wei Gu; Yu-jiang Fan

    2008-01-01

    A novel pH-sensitive nanoparticle drug delivery system (DDS) derived from natural polysaccharide pullulan for doxorubicin (DOX) release was prepared. Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups. DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate. This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX. Transmission electron microscope (TEM) and dynamic light scattering (DLS)characterization showed that the nanoparticles were spherical and their size was less than 100 nm. The DOX released from the nanoparticles in a pH-sensitive manner. In vitro cytotoxicity assay indicated the pullulan/DOX nanoparticles showed comparable cytotoxicity effect with free DOX on the 4T1 mouse breast cancer cells.

  15. Pumpless microfluidic platform for drug testing on human skin equivalents.

    Science.gov (United States)

    Abaci, Hasan Erbil; Gledhill, Karl; Guo, Zongyou; Christiano, Angela M; Shuler, Michael L

    2015-02-07

    Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies. In this study, we designed and developed a microfluidic platform that allows for long-term maintenance of full thickness human skin equivalents (HSE) which are comprised of both the epidermal and dermal compartments. The design is based on the physiologically relevant blood residence times in human skin tissue and allows for the establishment of an air-epidermal interface which is crucial for maturation and terminal differentiation of HSEs. The small scale of the design reduces the amount of culture medium and the number of cells required by 36 fold compared to conventional transwell cultures. Our HSE-on-a-chip platform has the capability to recirculate the medium at desired flow rates without the need for pump or external tube connections. We demonstrate that the platform can be used to maintain HSEs for three weeks with proliferating keratinocytes similar to conventional HSE cultures. Immunohistochemistry analyses show that the differentiation and localization of keratinocytes was successfully achieved, establishing all sub-layers of the epidermis after one week. Basal keratinocytes located at the epidermal-dermal interface remain in a proliferative state for three weeks. We use a transdermal transport model to show that the skin barrier function is maintained for three weeks. We also validate the capability of the HSE-on-a-chip platform to be used for drug testing purposes by examining the toxic effects of doxorubucin on skin cells and structure. Overall, the HSE-on-a-chip is a user-friendly and cost-effective in vitro platform for drug testing of candidate molecules for skin disorders.

  16. Rad51 and BRCA2--New molecular targets for sensitizing glioma cells to alkylating anticancer drugs.

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    Steve Quiros

    Full Text Available First line chemotherapeutics for brain tumors (malignant gliomas are alkylating agents such as temozolomide and nimustine. Despite growing knowledge of how these agents work, patients suffering from this malignancy still face a dismal prognosis. Alkylating agents target DNA, forming the killing lesion O(6-alkylguanine, which is converted into DNA double-strand breaks (DSBs that trigger apoptosis. Here we assessed whether inhibiting repair of DSBs by homologous recombination (HR or non-homologous end joining (NHEJ is a reasonable strategy for sensitizing glioma cells to alkylating agents. For down-regulation of HR in glioma cells, we used an interference RNA (iRNA approach targeting Rad51 and BRCA2, and for NHEJ we employed the DNA-PK inhibitor NU7026. We also assessed whether inhibition of poly(ADPribosyltransferase (PARP by olaparib would enhance the killing effect. The data show that knockdown of Rad51 or BRCA2 greatly sensitizes cells to DSBs and the induction of cell death following temozolomide and nimustine (ACNU. It did not sensitize to ionizing radiation (IR. The expression of O(6-methylguanine-DNA methyltransferase (MGMT abolished all these effects, indicating that O(6-alkylguanine induced by these drugs is the primary lesion responsible for the formation of DSBs and increased sensitivity of glioma cells following knockdown of Rad51 and BRCA2. Inhibition of DNA-PK only slightly sensitized to temozolomide whereas a significant effect was observed with IR. A triple strategy including siRNA and the PARP inhibitor olaparib further improved the killing effect of temozolomide. The data provides evidence that down-regulation of Rad51 or BRCA2 is a reasonable strategy for sensitizing glioma cells to killing by O(6-alkylating anti-cancer drugs. The data also provide proof of principle that a triple strategy involving down-regulation of HR, PARP inhibition and MGMT depletion may greatly enhance the therapeutic effect of temozolomide.

  17. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment.

    Science.gov (United States)

    Kosa, Peter; Ghazali, Danish; Tanigawa, Makoto; Barbour, Chris; Cortese, Irene; Kelley, William; Snyder, Blake; Ohayon, Joan; Fenton, Kaylan; Lehky, Tanya; Wu, Tianxia; Greenwood, Mark; Nair, Govind; Bielekova, Bibiana

    2016-01-01

    Therapeutic advance in progressive multiple sclerosis (MS) has been very slow. Based on the transformative role magnetic resonance imaging (MRI) contrast-enhancing lesions had on drug development for relapsing-remitting MS, we consider the lack of sensitive outcomes to be the greatest barrier for developing new treatments for progressive MS. The purpose of this study was to compare 58 prospectively acquired candidate outcomes in the real-world situation of progressive MS trials to select and validate the best-performing outcome. The 1-year pre-treatment period of adaptively designed IPPoMS (ClinicalTrials.gov #NCT00950248) and RIVITaLISe (ClinicalTrials.gov #NCT01212094) Phase II trials served to determine the primary outcome for the subsequent blinded treatment phase by comparing 8 clinical, 1 electrophysiological, 1 optical coherence tomography, 7 MRI volumetric, 9 quantitative T1 MRI, and 32 diffusion tensor imaging MRI outcomes. Fifteen outcomes demonstrated significant progression over 1 year (Δ) in the predetermined analysis and seven out of these were validated in two independent cohorts. Validated MRI outcomes had limited correlations with clinical scales, relatively poor signal-to-noise ratios (SNR) and recorded overlapping values between healthy subjects and MS patients with moderate-severe disability. Clinical measures correlated better, even though each reflects a somewhat different disability domain. Therefore, using machine-learning techniques, we developed a combinatorial weight-adjusted disability score (CombiWISE) that integrates four clinical scales: expanded disability status scale (EDSS), Scripps neurological rating scale, 25 foot walk and 9 hole peg test. CombiWISE outperformed all clinical scales (Δ = 9.10%; p = 0.0003) and all MRI outcomes. CombiWISE recorded no overlapping values between healthy subjects and disabled MS patients, had high SNR, and predicted changes in EDSS in a longitudinal assessment of 98 progressive MS

  18. Development of a sensitive outcome for economical drug screening for progressive multiple sclerosis treatment

    Directory of Open Access Journals (Sweden)

    Peter Kosa

    2016-08-01

    Full Text Available Therapeutic advance in progressive multiple sclerosis (MS has been very slow. Based on the transformative role magnetic resonance imaging (MRI contrast-enhancing lesions had on drug development for relapsing-remitting MS, we consider the lack of sensitive outcomes to be the greatest barrier for developing new treatments for progressive MS. The purpose of this study was to compare 58 prospectively-acquired candidate outcomes in the real-world situation of progressive MS trials, to select and validate the best-performing outcome.The one year pre-treatment period of adaptively-designed IPPoMS (ClinicalTrials.gov #NCT00950248 and RIVITaLISe (ClinicalTrials.gov #NCT01212094 Phase II trials served to determine the primary outcome for the subsequent blinded treatment phase by comparing eight clinical, one electrophysiological, one optical coherence tomography, seven MRI volumetric, nine quantitative T1 MRI, and 32 diffusion tensor imaging MRI outcomes. Fifteen outcomes demonstrated significant progression over one year (Δ in the predetermined analysis and seven out of these were validated in two independent cohorts. Validated MRI outcomes had limited correlations with clinical scales, relatively poor signal-to-noise ratios (SNR and recorded overlapping values between healthy subjects and MS patients with moderate-severe disability. Clinical measures correlated better, even though each reflects a somewhat different disability domain. Therefore, using machine-learning optimization, we developed a combinatorial weight-adjusted disability score (CombiWISE that integrates four clinical scales: expanded disability status scale (EDSS, Scripps neurological rating scale, 25 foot walk and nine hole peg test. CombiWISE outperformed all clinical scales (Δ=9.10%; p=0.0003 and all MRI outcomes. CombiWISE recorded no overlapping values between healthy subjects and disabled MS patients, had high SNR and predicted changes in EDSS in a longitudinal assessment of 98

  19. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment

    Science.gov (United States)

    Kosa, Peter; Ghazali, Danish; Tanigawa, Makoto; Barbour, Chris; Cortese, Irene; Kelley, William; Snyder, Blake; Ohayon, Joan; Fenton, Kaylan; Lehky, Tanya; Wu, Tianxia; Greenwood, Mark; Nair, Govind; Bielekova, Bibiana

    2016-01-01

    Therapeutic advance in progressive multiple sclerosis (MS) has been very slow. Based on the transformative role magnetic resonance imaging (MRI) contrast-enhancing lesions had on drug development for relapsing-remitting MS, we consider the lack of sensitive outcomes to be the greatest barrier for developing new treatments for progressive MS. The purpose of this study was to compare 58 prospectively acquired candidate outcomes in the real-world situation of progressive MS trials to select and validate the best-performing outcome. The 1-year pre-treatment period of adaptively designed IPPoMS (ClinicalTrials.gov #NCT00950248) and RIVITaLISe (ClinicalTrials.gov #NCT01212094) Phase II trials served to determine the primary outcome for the subsequent blinded treatment phase by comparing 8 clinical, 1 electrophysiological, 1 optical coherence tomography, 7 MRI volumetric, 9 quantitative T1 MRI, and 32 diffusion tensor imaging MRI outcomes. Fifteen outcomes demonstrated significant progression over 1 year (Δ) in the predetermined analysis and seven out of these were validated in two independent cohorts. Validated MRI outcomes had limited correlations with clinical scales, relatively poor signal-to-noise ratios (SNR) and recorded overlapping values between healthy subjects and MS patients with moderate-severe disability. Clinical measures correlated better, even though each reflects a somewhat different disability domain. Therefore, using machine-learning techniques, we developed a combinatorial weight-adjusted disability score (CombiWISE) that integrates four clinical scales: expanded disability status scale (EDSS), Scripps neurological rating scale, 25 foot walk and 9 hole peg test. CombiWISE outperformed all clinical scales (Δ = 9.10%; p = 0.0003) and all MRI outcomes. CombiWISE recorded no overlapping values between healthy subjects and disabled MS patients, had high SNR, and predicted changes in EDSS in a longitudinal assessment of 98 progressive MS

  20. Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

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    Matthew Arentz

    Full Text Available INTRODUCTION: Rapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB. However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection. METHODS: We searched MEDLINE, Embase and the Cochrane Library through January 1, 2012. For each rapid test, we determined pooled sensitivity and specificity estimates using a hierarchical random effects model. Predictive values of the tests were determined at different prevalence rates of rifampicin resistance and MDR-TB. RESULTS: We identified 60 publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI assay, Nitrate Reductase Assay (NRA and MODS tests: for all tests, negative predictive values were high when rifampicin resistance prevalence was ≤ 30%. However, positive predictive values were considerably reduced for the INNO-LiPA Rif. TB assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was < 5%. LIMITATIONS: In many studies, it was unclear whether patient selection or index test performance could have introduced bias. In addition, we were unable to evaluate critical concentration thresholds for the colorimetric tests. DISCUSSION: Rapid tests for rifampicin resistance alone cannot accurately predict rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin resistance. However, in areas with a high prevalence of rifampicin resistance and MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.

  1. Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

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    Kirsi Ketola

    Full Text Available BACKGROUND: Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects. METHODS AND FINDINGS: In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression. CONCLUSIONS: Taken together, our results propose novel combinatorial approaches to inhibit

  2. Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

    Science.gov (United States)

    Ketola, Kirsi; Kallioniemi, Olli; Iljin, Kristiina

    2012-01-01

    Background Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects. Methods and Findings In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression. Conclusions Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell

  3. Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells

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    Olah Eva

    2006-11-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD, AIDS related immunoblastic lymphomas (ARL and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP. The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23–50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders. Methods As lymphoblastoid cell lines (LCLs are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope. Results Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel. Conclusion Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified.

  4. Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression.

    Science.gov (United States)

    Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria

    2010-08-16

    The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity.

  5. Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data [version 1; referees: 2 approved

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    Linh Nguyen

    2016-12-01

    Full Text Available Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than K-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug. Regarding overall classification performance, about two thirds of the drugs are better predicted by multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: We now know that this type of models can predict in vitro tumour response to these drugs. These models can thus be further investigated on in vivo tumour models.

  6. Contact sensitivity in mice evaluated by means of ear swelling and a radiometric test

    Energy Technology Data Exchange (ETDEWEB)

    Baeck, O.; Larsen, A.

    1982-04-01

    Contact sensitivity to picryl chloride was investigated by means of the ear swelling test and a radiometric test in order to establish optimal experimental conditions for these assays. Contact sensitivity was demonstrated as soon as 2 days after sensitization, with a maximum reaction 3-4 days after sensitization, when a 48 hr test reaction was registered. The test reaction was followed for 72 hr and maximum was arrived at after 24 hr and 48 hr for the ear swelling test and the radiometric test, respectively. Optimal sensitization was reached with a 7% solution of picryl chloride and a maximum test reaction was found with 0.75-1.0% picryl chloride. It is concluded that both assays measure contact sensitivity in quantitative terms and a future replacement of the guinea pig maximization test is discussed.

  7. pH-sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method.

    Science.gov (United States)

    Laouini, Abdallah; Koutroumanis, Konstantinos P; Charcosset, Catherine; Georgiadou, Stella; Fessi, Hatem; Holdich, Richard G; Vladisavljević, Goran T

    2013-09-25

    A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, Mn (9200 or 10,400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m(-2) h(-1) of the organic phase (a 1 mg mL(-1) solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of ~75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of -19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions.

  8. Drug Testing. ERIC Digest Series Number EA35 (Revised).

    Science.gov (United States)

    Klauke, Amy; Hadderman, Margaret

    Despite privacy concerns, school administrators are feeling pressure to adopt urgent measures to keep drugs and alcohol from further endangering our youth's well-being and undermining staff performance. This urgency is reinforced by a national anti-drug campaign and Congressional passage of the Drug-Free Workplace Act (1988) and the Drug-Free…

  9. Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys1

    Institute of Scientific and Technical Information of China (English)

    Su-qing CHEN; Hai-feng ZHAI; Yan-ying CUI; Jie SHI; Bernard LE FOLL; Lin LU

    2007-01-01

    Aim: Clonidine is an α2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus mon-keys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. Methods: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic)dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. Results:Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized re-sponses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previ-ously treated with clonidine. Conclusion: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may re-duce subsequent effects of drugs of abuse after prolonged abstinence.

  10. Sensitive Determination of Sertraline in Commercial Drugs and Its Stability Check in Simulated Gastric Juice.

    Science.gov (United States)

    Koçoğlu, Elif Seda; Bakırdere, Sezgin; Keyf, Seyfullah

    2016-11-01

    A sensitive analytical method was developed for the determination of sertraline in commercial drug samples by using GC-MS. The selected-ion monitoring mode was used at the most sensitive m/z 274 to obtain a lower detection limit. LOD/LOQ values were obtained as 1.6/5.4 ng/mL for sertraline under the optimum conditions. The calibration plot was linear between 5.0 and 2000 ng/mL with the correlation coefficient of 0.9999. The validated method was successfully applied to three different brands of drug samples for both qualitative and quantitative measurement of sertraline. In this experiment, four replicate extractions were performed for each brand, and the results were compared to the values written on the labels of the drug brands. Spiking experiments were also performed to check the effect of the matrixes on the determination, and it was observed that there was no shift in the retention time of the analyte. In addition, simulated gastric juice experiments were performed to check the stability of sertraline in the stomach for 240 min, and it was observed that there was no change in the structure of the analyte.

  11. 76 FR 34086 - Mandatory Guidelines for Federal Workplace Drug Testing Programs; Request for Information...

    Science.gov (United States)

    2011-06-10

    ... Federal Workplace Drug Testing Programs; Request for Information Regarding Specific Issues Related to the Use of the Oral Fluid Specimen for Drug Testing AGENCY: Substance Abuse and Mental Health Services... Mandatory Guidelines for Federal Workplace Drug Testing Programs (oral fluid specimen). DATES: Comment Close...

  12. 49 CFR 40.123 - What are the MRO's responsibilities in the DOT drug testing program?

    Science.gov (United States)

    2010-10-01

    ... drug testing program? 40.123 Section 40.123 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the Verification Process § 40.123 What are the MRO's responsibilities in the DOT drug testing program? As an MRO...

  13. Drug Testing Guidelines and Practices for Juvenile Probation and Parole Agencies.

    Science.gov (United States)

    American Probation and Parole Association, Lexington, KY.

    This document, intended as a resource manual, provides guidelines on drug testing. These topics are covered: (1) National Institute on Drug Abuse guidelines applicability; (2) introduction to legal issues, drug testing in juvenile probation and parole, and juvenile law; (3) mission of a juvenile parole agency; (4) purpose of testing; (5) drug…

  14. 78 FR 39190 - Revisions to Fitness for Duty Programs' Drug Testing Requirements

    Science.gov (United States)

    2013-07-01

    ...-2009-0225] RIN 3150-AI67 Revisions to Fitness for Duty Programs' Drug Testing Requirements AGENCY... regulations regarding drug testing requirements in NRC licensees' fitness for duty programs. The regulatory... select drug testing provisions in the U.S. Department of Health and Human Services' ``Mandatory...

  15. 75 FR 76478 - Mandatory Guidelines for Federal Workplace Drug Testing Programs

    Science.gov (United States)

    2010-12-08

    ... HUMAN SERVICES Mandatory Guidelines for Federal Workplace Drug Testing Programs AGENCY: Substance Abuse... Department of Health and Human Services (HHS) Mandatory Guidelines for Federal Workplace Drug Testing... drug testing results that seek approval by the Secretary must submit their qualifications and a sample...

  16. 49 CFR 40.31 - Who may collect urine specimens for DOT drug testing?

    Science.gov (United States)

    2010-10-01

    ... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Urine Collection Personnel § 40.31 Who may collect urine specimens for DOT drug testing? (a) Collectors meeting the requirements of this subpart are the only persons authorized to collect urine specimens for DOT drug testing. (b) A collector must meet...

  17. On the Comparison of Interpersonal Sensitivity and Assertiveness between Drug-Dependent Persons and Ordinary People

    Directory of Open Access Journals (Sweden)

    Babak Vojudi

    2015-02-01

    Full Text Available Objective: The present study was aimed at comparing interpersonal sensitivity and assertiveness between drug-dependent persons and ordinary people. Method: The research method was causal-comparative. The statistical population of the study consisted of all narcotic addicts of Tabriz City who referred to Addiction Treatment Centers while the research was being conducted. The number of 30 addicted persons was selected through cluster sampling and 30 ordinary persons as control group through convenience sampling method. Gmbryl & Ritchie’s assertiveness questionnaire (1975 and Boyce & Parker’s Interpersonal Sensitivity Measure (IPSM 1989 were used for data collection purposes. Results: The results showed that there was a statistically significant difference between two groups in terms of interpersonal sensitivity and assertiveness. The addicts showed less assertiveness and more interpersonal sensitivity in comparison with their healthy counterparts. Conclusion: The findings show that people who are unable to express themselves and exert sensitivity in interpersonal relationships are more likely at high risk of substance dependence. However, it is possible to prevent these persons from turning to addiction by teaching them these skills.

  18. Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay.

    Science.gov (United States)

    Ellis, Giovanina M; Vlaskin, Tatyana A; Koth, Andrew; Vaz, Louise E; Dross, Sandra E; Beck, Ingrid A; Frenkel, Lisa M

    2013-09-01

    Oligonucleotide ligation assay (OLA) is a highly specific and relatively simple method to detect point mutations encoding HIV-1 drug-resistance, which can detect mutants comprising ≥2-5% of the viral population. Nevirapine (NVP), tenofovir (TDF) and lamivudine (3TC) are antiretroviral (ARV) drugs used worldwide for treatment of HIV infection and prevention of mother-to-child-transmission. Adapting the OLA to detect multiple mutations associated with HIV resistance to these ARV simultaneously would provide an efficient tool to monitor drug resistance in resource-limited settings. Known proportions of mutant and wild-type plasmids were used to optimize a multiplex OLA for detection of K103N, Y181C, K65R, and M184V in HIV subtypes B and C, and V106M and G190A in subtype C. Simultaneous detection of two mutations was impaired if probes annealed to overlapping regions of the viral template, but was sensitive to ≥2-5% when testing codons using non-overlapping probes. PCR products from HIV-subtype B- and C-infected individuals were tested by multiplex-OLA and compared to results of single-codon OLA. Multiplex-OLA detected mutations at codon pairs 103/181, 106/190 and 65/184 reliably when compared to singleplex-OLA in clinical specimens. The multiplex-OLA is sensitive and specific and reduces the cost of screening for NVP, TDF and/or 3TC resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy.

    Science.gov (United States)

    Chang, Danfeng; Gao, Yongfeng; Wang, Lijun; Liu, Gan; Chen, Yuhan; Wang, Teng; Tao, Wei; Mei, Lin; Huang, Laiqiang; Zeng, Xiaowei

    2016-02-01

    A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs-DES-PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs-DES-PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs-DES and MSNs-DES-PDA were totally different, and the drug release of MSNs-DES-PDA accelerated with increasing acidity. MSNs-DES-PDA can be internalized into cells. In vitro experiments demonstrated that MSNs-DES-PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy.

  20. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

    Science.gov (United States)

    Hong, Zai-Fa; Zhao, Wen-Xiu; Yin, Zhen-Yu; Xie, Cheng-Rong; Xu, Ya-Ping; Chi, Xiao-Qin; Zhang, Sheng; Wang, Xiao-Min

    2015-01-01

    Cholangiocarcinoma (CCA), a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU) was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI) capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  1. Magnesium intracellular content and distribution map in drug-resistant and -sensitive whole cells

    Directory of Open Access Journals (Sweden)

    Emil Malucelli

    2014-01-01

    Full Text Available Magnesium (Mg plays crucial structural and regulatory roles within cells. Despite the extensive amount of data about the biochemistry of Mg, a complete picture of its regulation and cellular homeostasis is lacking. Thanks to recent improvements in third generation synchrotron X-ray sources, X-ray fluorescence microscopy (XRFM is becoming a highly sensitive method for mapping elemental distributions in cells. XRFM maps the element content but not the concentration, which is a relevant variable in a biological context. We tackled this issue by combining XRFM with atomic force microscopy that was used to obtain morphological information of the sample. The aim of the present study was to compare the content and the distribution of Mg in drug-resistant and -sensitive tumor cell lines. Our data has shown a massive increase of Mg in LoVo drug-resistant cells. Moreover, the map of intracellular Mg showed marked differences in the pattern distribution between sensitive and resistant cells.

  2. Design, validation, and absolute sensitivity of a novel test for the molecular detection of avian pneumovirus.

    Science.gov (United States)

    Cecchinato, Mattia; Catelli, Elena; Savage, Carol E; Jones, Richard C; Naylor, Clive J

    2004-11-01

    This study describes attempts to increase and measure sensitivity of molecular tests to detect avian pneumovirus (APV). Polymerase chain reaction (PCR) diagnostic tests were designed for the detection of nucleic acid from an A-type APV genome. The objective was selection of PCR oligonucleotide combinations, which would provide the greatest test sensitivity and thereby enable optimal detection when used for later testing of field materials. Relative and absolute test sensitivities could be determined because of laboratory access to known quantities of purified full-length DNA copies of APV genome derived from the same A-type virus. Four new nested PCR tests were designed in the fusion (F) protein (2 tests), small hydrophobic (SH) protein (1 test), and nucleocapsid (N) protein (1 test) genes and compared with an established test in the attachment (G) protein gene. Known amounts of full-length APV genome were serially diluted 10-fold, and these dilutions were used as templates for the different tests. Sensitivities were found to differ between the tests, the most sensitive being the established G test, which proved able to detect 6,000 copies of the G gene. The G test contained predominantly pyrimidine residues at its 3' termini, and because of this, oligonucleotides for the most sensitive F test were modified to incorporate the same residue types at their 3' termini. This was found to increase sensitivity, so that after full 3' pyrimidine substitutions, the F test became able to detect 600 copies of the F gene.

  3. Sensitivity and specificity of neuropsychological tests for dementia ...

    African Journals Online (AJOL)

    specificity of a battery of neuropsychological tests in a sample of .... psychological scores and 95% confidence intervals .... psychological tests in elderly participants ..... verbal fluency tasks in the detection of dementia of the Alzheimer type.

  4. Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests.

    Science.gov (United States)

    Musshoff, F; Driever, F; Lachenmeier, K; Lachenmeier, D W; Banger, M; Madea, B

    2006-01-27

    Urine as well as head and pubic hair samples from drug abusers were analysed for opiates, cocaine and its metabolites, amphetamines, methadone and cannabinoids. Urine immunoassay results and the results of hair tests by means of gas chromatography-mass spectrometry were compared to the self-reported data of the patients in an interview protocol. With regard to the study group, opiate abuse was claimed from the majority in self-reports (89%), followed by cannabinoids (55%), cocaine (38%), and methadone (32%). Except for opiates the comparison between self-reported drug use and urinalysis at admission showed a low correlation. In contrast to urinalysis, hair tests revealed consumption in more cases. There was also a good agreement between self-reports of patients taking part in an official methadone maintenance program and urine test results concerning methadone. However, hair test results demonstrated that methadone abuse in general was under-reported by people who did not participate in a substitution program. Comparing self-reports and the results of hair analyses drug use was dramatically under-reported, especially cocaine. Cocaine hair tests appeared to be highly sensitive and specific in identifying past cocaine use even in settings of negative urine tests. In contrast to cocaine, hair lacks sensitivity as a detection agent for cannabinoids and a proof of cannabis use by means of hair analysis should include the sensitive detection of the metabolite THC carboxylic acid in the lower picogram range.

  5. Swelling and drug releasing properties of poly(N-isopropylacrylamide) thermo-sensitive copolymer gels

    Institute of Scientific and Technical Information of China (English)

    Chunyue PAN; Qingde LONG; Dian YU; Yanping RAO; Nianqian WU; Xingcui LI

    2008-01-01

    A series of N,isopropylacrylamide (NIPAAm)copolymer gels with different hydrophilicities were prepared from NIPAAm, hydrophilic acrylamide (AAm) and hydrophobic butyl methacrylate (BMA). The swelling and thermo,responsive properties of PNIPAAm P (NIPAm,co,BMA) and P(NIPAm,co,AAm) copolymer hydrogels were investigated. The drug loading and releasing behaviors for two kinds of model drug with different hydrophilicities were studied. The result shows that the copolymer gels present negative thermo,sensitivities. The lower critical solution temperature (LCST), equilibrium swelling degree and the initial swelling rate increase as the hydrophilicity of gels increases when the temperature is below the LCST. With increasing gel hydrophilicity the loading ratio for sodium salicylate increases, while for salicylic acid, the reverse is observed. The initial drug releasing rate of sodium salicylate and salicylic acid also increase with increasing gel hydrophilicity. The initial drug releasing rate of sodium salicylate is significantly higher than that of salicylic acid. For salicylic acid which is less hydrophilic, the equilibrium releasing ratio at high temperature is lower than that at low temperature while for sodium salicylate which is more hydrophilic, the equilibrium releasing ratio at high temperature is almost the same as that at low temperature. Equilibrium releasing ratios of the three gels are significantly different from each other for salicylic acid when the temperature is below LCST while the equilibrium releasing ratios of the three gels are all 100% for sodium salicylate.

  6. Differential sensitivity of RIP3-proficient anddeficient murine fibroblasts to camptothecinanticancer drugs

    Institute of Scientific and Technical Information of China (English)

    Jin-xue HE; Bing YU; Guang CHEN; Ze-hong MIAO; Ying-qing WANG; Jian-ming FENG; Jia-xin LI; Lei XU; Xiao-hua LI; Wei WANG; Xia-juan HUAN; YiJIANG

    2012-01-01

    Dear Edltor,Receptor-interacting protein 3 (RIP3) is a serine/threonine protein kinase,which has extensive substrates including its cognate kinase RIP1 and multiple metabolic enzymes involv-ing oxidative phosphorylation[1,2].RIP3 has been shown to be essential for development,immunity and some physiological or pathophysiological responses to exogenous and endoge-nous stimuli[3-5].In 2009,three groups independently reported that RIP3 acted as a molecular switch between apoptosis and necrosis (also called as necroptosis)[6-8].Specifically,RIP3could turn tumor necrosis factor (TNF)-induced cell death from apoptosis to necrosis[6].Most of small-molecule antican-cer drugs elicit their anticancer effects via apoptotic induc-tion[9].However,it is unclear whether RIP3 affects the cellular sensitivity to small-molecule anticancer drugs.

  7. [Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].

    Science.gov (United States)

    Korenaga, Masaaki; Kawaguchi, Koutaro; Korenaga, Keiko; Uchida, Kouichi; Sakaida, Iso

    2006-06-01

    Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.

  8. Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

    DEFF Research Database (Denmark)

    Swanton, Charles; Szallasi, Zoltan Imre; Brenton, James D.

    2008-01-01

    The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and 5-fluorouracil, targeted agents such as trastuzumab and inhibitors of AKT and Poly(ADP-ribose) polymerase (PARP......) as well as endocrine therapies such as tamoxifen. Given the limited power of microarray signatures to predict therapeutic response in associative studies of small clinical trial cohorts, the use of functional genomic data combined with expression or sequence analysis of genes and microRNAs implicated...... in drug response in human tumours may provide a more robust method to guide adjuvant treatment strategies in breast cancer that are transferable across different expression platforms and patient cohorts....

  9. Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives.

    Science.gov (United States)

    Schön, T; Miotto, P; Köser, C U; Viveiros, M; Böttger, E; Cambau, E

    2017-03-01

    Drug-resistance testing, or antimicrobial susceptibility testing (AST), is mandatory for Mycobacterium tuberculosis in cases of failure on standard therapy. We reviewed the different methods and techniques of phenotypic and genotypic approaches. Although multiresistant and extensively drug-resistant (MDR/XDR) tuberculosis is present worldwide, AST for M. tuberculosis (AST-MTB) is still mainly performed according to the resources available rather than the drug-resistance rates. Phenotypic methods, i.e. culture-based AST, are commonly used in high-income countries to confirm susceptibility of new cases of tuberculosis. They are also used to detect resistance in tuberculosis cases with risk factors, in combination with genotypic tests. In low-income countries, genotypic methods screening hot-spot mutations known to confer resistance were found to be easier to perform because they avoid the culture and biosafety constraint. Given that genotypic tests can rapidly detect the prominent mechanisms of resistance, such as the rpoB mutation for rifampicin resistance, we are facing new challenges with the observation of false-resistance (mutations not conferring resistance) and false-susceptibility (mutations different from the common mechanism) results. Phenotypic and genotypic approaches are therefore complementary for obtaining a high sensitivity and specificity for detecting drug resistances and susceptibilities to accurately predict MDR/XDR cure and to gather relevant data for resistance surveillance. Although AST-MTB was established in the 1960s, there is no consensus reference method for MIC determination against which the numerous AST-MTB techniques can be compared. This information is necessary for assessing in vitro activity and setting breakpoints for future anti-tuberculosis agents. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. 78 FR 68076 - Request for Information on Alternative Skin Sensitization Test Methods and Testing Strategies and...

    Science.gov (United States)

    2013-11-13

    ... workers and consumers exposed to skin-sensitizing chemicals and products. Pesticides and other marketed... relationship (SAR) models to predict skin sensitization. NICEATM collaboration with industry scientists to... sensitization. Participating in validation management groups sponsored by ICATM partner organizations to...

  11. Evaluation of ten oral fluid point-of-collection drug-testing devices.

    Science.gov (United States)

    Walsh, J Michael; Crouch, Dennis J; Danaceau, Jonathan P; Cangianelli, Leo; Liddicoat, Laura; Adkins, Randy

    2007-01-01

    Previously, the laboratory evaluations of six point-of-collection oral fluid (POC-OF) drug testing devices were reported. Four additional devices, Oralstat (American Bio Medica); SmartClip (Envitec); Impact (LifePoint); and OraLine IV s.a.t (Sun Biomedical Laboratories), were recently evaluated for their ability to meet the claimed (and proposed) cutoff concentrations set by the manufacturers for the detection of amphetamine(s), cocaine/metabolite, opiates, and cannabinoids (Oralstat also benzodiazepines). With the exception of the Sun Biomedical device, actual false-positive results were not encountered. Most devices performed well for the detection of opiates and amphetamine(s), but approximately half had amphetamine(s) cutoff concentrations greater than that proposed by the Substance Abuse and Mental Health Services Administration (SAMHSA). Only three devices had cocaine cutoffs less than or equal to 20 ng/mL (SAMHSA), and a number of false-negative results were obtained. The devices still were not capable of detecting Delta(9)-tetrahydrocannabinol at 4 ng/mL (SAMHSA). However, sensitivities improved since the initial studies, and approximately half of the devices met the THC-COOH cutoff proposed by SAMHSA. Results from the current and previous evaluations are presented in the paper and indicate that the sensitivity and performance of commercial OF drug testing devices is improving, but remains problematic for the reliable detection of cannabinoid use.

  12. Sensitivity during the forced swim test is a key factor in evaluating the antidepressant effects of abscisic acid in mice.

    Science.gov (United States)

    Qi, Cong-Cong; Shu, Yu-Mian; Chen, Fang-Han; Ding, Yu-Qiang; Zhou, Jiang-Ning

    2016-03-01

    Abscisic acid (ABA), a crucial phytohormone, is distributed in the brains of mammals and has been shown to have antidepressant effects in the chronic unpredictable mild stress test. The forced swim test (FST) is another animal model that can be used to assess antidepressant-like behavior in rodents. Here, we report that the antidepressant effects of ABA are associated with sensitivities to the FST in mice. Based on mean immobility in the 5-min forced swim pre-test, ICR mice were divided into short immobility mice (SIM) and long immobility mice (LIM) substrains. FST was carried out 8 days after drug administration. Learned helplessness, as shown by increased immobility, was only observed in SIM substrain and could be prevented by an 8-day ABA treatment. Our results show that ABA has antidepressant effects in SIM substrain and suggest that mice with learned helplessness might be more suitable for screening potential antidepressant drugs.

  13. Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug.

    Science.gov (United States)

    Zhang, Wuxia; Dong, Dongqi; Li, Peng; Wang, Dongdong; Mu, Haibo; Niu, Hong; Duan, Jinyou

    2016-03-30

    Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Microfluidic conceived pH sensitive core-shell particles for dual drug delivery.

    Science.gov (United States)

    Khan, Ikram Ullah; Stolch, Lukas; Serra, Christophe A; Anton, Nicolas; Akasov, Roman; Vandamme, Thierry F

    2015-01-15

    In current study, we report on the synthesis of core-shell microparticles for dual drug delivery by means of a two co-axial microfluidic device and online UV assisted free radical polymerization. Before developing pH-sensitive particles, ketoprofen loaded poly(methyl acrylate) core-ranitidine HCl loaded poly(acrylamide) shell particles were produced. Influence of inner and outer phases flow rates on particle size, shape, core diameter, shell thickness, and drug release properties was studied. All the particles were monodispersed with coefficient of variation below 5%. Furthermore, their diameter ranged from 100 to 151 μm by increasing continuous (Qc) to middle (Qm) phase flow rate ratio (Qc/Qm). Core diameter varied from 58 to 115 μm by decreasing middle (Qm) to inner (Qi) phase flow rate ratio (Qm/Qi) at constant continuous phase flow rate as confirmed by SEM images. It was observed that an optimum concentration of acrylamide (30 wt%) and an appropriate combination of surfactants were necessary to get core-shell particles otherwise Janus structure was obtained. FTIR confirmed the complete polymerization of core and shell phases. MTT assay showed variation in viability of cells under non-contact and contact conditions with less cytotoxicity for the former. Under non-contact conditions LD50 was 3.1mg/mL. Release studies in USP phosphate buffer solution showed simultaneously release of ketoprofen and ranitidine HCl for non pH-sensitive particles. However, release rates of ranitidine HCl and ketoprofen were higher at low and high pH respectively. To develop pH-sensitive particles for colon targeting, the previous shell phase was admixed with few weight percentage of pH sensitive carboxyethyl acrylate monomer. Core and shell contained the same hydrophobic and hydrophilic model drugs as in previous case. The pH-sensitive shell prevented the release of the two entrapped molecules at low pH while increasing significantly their release rate at higher pH with a maximum

  15. 10 CFR 26.65 - Pre-access drug and alcohol testing.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Pre-access drug and alcohol testing. 26.65 Section 26.65... § 26.65 Pre-access drug and alcohol testing. (a) Purpose. This section contains pre-access testing... rely on the results of those drug and alcohol tests to meet the requirements for pre-access testing in...

  16. An Analysis of the Effectiveness of the Air Force Drug Testing Program and Four Potential Modifications

    Science.gov (United States)

    1993-09-01

    Another hair testing methodology uses an enzyme immunoassay (EIA) technique, which is also commonly used for testing urine for drugs in commercial...1992, urine specimens collected for the USAF Drug Testing Program were tested for the following drugs: Cannabis (Marijuana), Cocaine, Amphetamine ...abuse in the previous 12 months, and of the 196,476 urine specimens tested in fiscal year 1992, less than 0.5 percent testea positive (2:14; 8:Ch 5, 12

  17. Sensitivity and specificity of the nickel spot (dimethylglyoxime) test

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Skare, Lizbet; Lundgren, Lennart;

    2010-01-01

    The accuracy of the dimethylglyoxime (DMG) nickel spot test has been questioned because of false negative and positive test reactions. The EN 1811, a European standard reference method developed by the European Committee for Standardization (CEN), is fine-tuned to estimate nickel release around...... the limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test....

  18. Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A

    Directory of Open Access Journals (Sweden)

    Shinde Ravikumar B

    2012-10-01

    Full Text Available Abstract Background Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms. Methods Combinations of five antifungal drugs- fluconazole (FLC, voriconazole (VOR, caspofungin (CSP, amphotericin B (AmB and nystatin (NYT with cyclosporine A (CSA were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI of combination effects. Biofilm growth was analyzed using XTT-metabolic assay. Results MICs of various antifungal drugs for planktonic growth of C. albicans were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively. Conclusions The combinations with CSA resulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated C. albicans infections.

  19. Evaluation of rapid alternative methods for drug susceptibility testing in clinical isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Luciano Mengatto

    2006-08-01

    Full Text Available A study was carried out to compare the performance of a commercial method (MGIT and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA, microscopic observation drug susceptibility (MODS assay, MTT test, and broth microdilution method (BMM. A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87% whereas for streptomycin, sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety, they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8; more standardization is needed for ethambutol.

  20. 副猪嗜血杆菌江西分离株药物敏感性及四环素耐药基因tet(B)分析%Drug sensitive tests and analysis of tetracycline resistance gene tet(B ) of Haemophilus parasuis isolates

    Institute of Scientific and Technical Information of China (English)

    宋德平; 肖根辉; 王萍; 何后军; 邬向东; 黄冬艳; 邓舜洲; 张文波

    2011-01-01

    为了解副猪嗜血杆菌江西株的药物敏感性及其耐药基因,本实验采用K-B法测定分离株对57种药物的敏感性,结果显示20株副猪嗜血杆菌均对阿洛西林和万古霉素敏感,80%及以上的分离株对氨苄西林\\舒巴坦、阿莫西林\\棒酸等高度敏感.但分离株对恩诺沙星、氨曲南、四环素等的耐受性较强,某些菌株对多种药物具有抗性,其中6株菌能够耐受5种药物,5株菌能够耐受12种药物,3株菌能够耐受13种药物,甚至有2株菌能够耐受多达22种药物.将江西分离株的药物敏感性结果与其它国家或地区以及不同时间分离菌株的结果相比较表明,不同地区及不同时间段分离的菌株药物敏感性存在较大差异.为探索副猪嗜血杆菌耐药的分子机制,本研究设计引物并建立了检测四环素耐药基因tet(B)的PCR方法.运用所建立的方法检测江西株tet(B)基因,在15株四环素耐药菌株中检测出其中9株菌存在该基因,推测tet(B)可能是介导该菌对四环素耐药的主要分子机制之一.%To investigate the antibiotic sensitivity and genes mediated the insistence in Haemophilus parasuis, A total of 20 Jiangxi H. Parasuis isolates were tested with 57 antibiotics by a K-B method. The results showed that all the isolates were susceptible to azlocilin, enrofloxacin and vancomycin, while eighty percent of the isolates was susceptible to Ampicillin/ Sulbatam, Amoxicillin/Clavulanic acid, etc. Howerver, a high level of resistance was found for Enrofloxacin, Aztreonam, Tetracycline etc. Several multiresistance patterns were found among the isolates, of which resistant to 5 or even to 22 antibiotics. Furthermore, A PCR assay was established to detect the tetracycline drug resistance gene tet(B) for the H. Parasuis isolates and nine of the 15 Jiangxi isolates resistanted to tetracycline were positive, which indicated that tet(B) might be one of the main molecular mechanisms mediated the

  1. 49 CFR 655.41 - Pre-employment drug testing.

    Science.gov (United States)

    2010-10-01

    ... applicant to perform a safety-sensitive function for the first time, the employer must ensure that the... employer may not allow a covered employee, including an applicant, to perform a safety-sensitive function... employee from a nonsafety-sensitive function to a safety-sensitive function until the employee takes a pre...

  2. Creatinine normalization of workplace urine drug tests: does it make a difference?

    Science.gov (United States)

    Price, James W

    2013-01-01

    This study examines the effect of creatinine normalization on urine drug concentrations of 5 substances (amphetamines, cocaine, marijuana, opiates, and phencyclidine) and how this affects the proportion of reported positives. The Wilcoxon matched-pairs signed-ranks test was used to compare the mean prenormalization urinary drug concentration with the mean postnormalization urinary drug concentration. Frequency analysis was performed on dichotomous drug test results and the information was used to complete McNemar testing for each drug to determine the difference of proportions for prenormalization positive drug tests to postnormalization positive drug test. Each drug tested (N = 4460) was found to have a statistically significant increase in mean urinary drug concentration after creatinine normalization with effect sizes ranging from small to medium with cocaine having the largest effect size (r = 0.229) and phencyclidine having the lowest effect size (r = 0.121). The differences in proportion of dichotomous results between study and control groups for drugs tested were compared with the McNemar test. Each drug had a statistically significant (P = 0.0010) increase of positive drug tests. This result indicates that specimen dilution does affect the number of laboratory-positive results confirmed.

  3. Codelivery of antitumor drug and gene by a pH-sensitive charge-conversion system.

    Science.gov (United States)

    Guan, Xiuwen; Li, Yanhui; Jiao, Zixue; Lin, Lin; Chen, Jie; Guo, Zhaopei; Tian, Huayu; Chen, Xuesi

    2015-02-11

    In the present study, a gene and drug codelivery system was developed by electrostatic binding of polyethylenimine-poly(l-lysine)-poly(l-glutamic acid) (PELG), polyethylenimine (PEI), cis-aconityl-doxorubicin (CAD), and DNA. Zeta potential and drug release analysis confirmed the pH-responsive charge conversion and acid-sensitive drug release functional properties of the PELG/PEI/(DNA+CAD) system. Gel retardation assay and transfection experiment showed the codelivery system had effective DNA binding ability and good transfection efficiency on HepG2 cells. The therapeutic gene p53 was further employed to study its combinational effects with CAD. Cytotoxicity assay showed the half inhibitory concentration (IC50) of the PELG/PEI/(p53+CAD) codelivery system was lower than that of the gene or the drug delivery system. Confocal laser scanning microscopy (CLSM) showed that the drug and gene could be delivered into the cells simultaneously. A significant increase of p53 gene expression was achieved after HepG2 cells treated by PELG/PEI/(p53+CAD) codelivery system. The apoptosis experiment indicated clearly that the codelivery system could lead an effective apoptosis on tumor cells, which was beneficial for the treatment of cancer. The biodistribution and tumor accumulation of the codelivery system was explored via in vivo imaging in subcutaneous xenograft and in situ tumor models. The tumor and some major organs were excised and imaged, and the results showed that the codelivery system can accumulate efficiently in tumor for both tumor models. It can be suggested from the above results that the PELG/PEI/(DNA+CAD) codelivery system will have great potential applications in cancer therapy.

  4. Sensitivity and specificity of the nickel spot (dimethylglyoxime) test

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Skare, Lizbet; Lundgren, Lennart

    2010-01-01

    the limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test....

  5. Sports drug testing using complementary matrices: Advantages and limitations.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Tretzel, Laura; Schänzer, Wilhelm

    2016-10-25

    Today, routine doping controls largely rely on testing whole blood, serum, and urine samples. These matrices allow comprehensively covering inorganic as well as low and high molecular mass organic analytes relevant to doping controls and are collecting and transferring from sampling sites to accredited anti-doping laboratories under standardized conditions. Various aspects including time and cost-effectiveness as well as intrusiveness and invasiveness of the sampling procedure but also analyte stability and breadth of the contained information have been motivation to consider and assess values potentially provided and added to modern sports drug testing programs by alternative matrices. Such alternatives could be dried blood spots (DBS), dried plasma spots (DPS), oral fluid (OF), exhaled breath (EB), and hair. In this review, recent developments and test methods concerning these alternative matrices and expected or proven contributions as well as limitations of these specimens in the context of the international anti-doping fight are presented and discussed, guided by current regulations for prohibited substances and methods of doping as established by the World Anti-Doping Agency (WADA). Focusing on literature published between 2011 and 2015, examples for doping control analytical assays concerning non-approved substances, anabolic agents, peptide hormones/growth factors/related substances and mimetics, β2-agonists, hormone and metabolic modulators, diuretics and masking agents, stimulants, narcotics, cannabinoids, glucocorticoids, and beta-blockers were selected to outline the advantages and limitations of the aforementioned alternative matrices as compared to conventional doping control samples (i.e. urine and blood/serum).

  6. Portable Upconversion Nanoparticles-Based Paper Device for Field Testing of Drug Abuse.

    Science.gov (United States)

    He, Mengyuan; Li, Zhen; Ge, Yiying; Liu, Zhihong

    2016-02-01

    We report the first portable upconversion nanoparticles (UCNPs)-based paper device for road-side field testing of cocaine. Upon the recognition of cocaine by two pieces of rationally designed aptamer fragments, the luminescence of UCNPs immobilized on the paper is quenched by Au nanoparticles (AuNPs), which indicates the cocaine concentration. This device can give quantitative results in a short time with high sensitivity using only a smartphone as the apparatus. Moreover, this device is applicable in human saliva samples, and it also can be used to monitor the cocaine content change in blood samples. The results of this work demonstrate the prospect of developing UCNPs-based paper devices for field testing of drug abuse.

  7. Smart licensing and environmental flows: Modeling framework and sensitivity testing

    Science.gov (United States)

    Wilby, R. L.; Fenn, C. R.; Wood, P. J.; Timlett, R.; Lequesne, T.

    2011-12-01

    Adapting to climate change is just one among many challenges facing river managers. The response will involve balancing the long-term water demands of society with the changing needs of the environment in sustainable and cost effective ways. This paper describes a modeling framework for evaluating the sensitivity of low river flows to different configurations of abstraction licensing under both historical climate variability and expected climate change. A rainfall-runoff model is used to quantify trade-offs among environmental flow (e-flow) requirements, potential surface and groundwater abstraction volumes, and the frequency of harmful low-flow conditions. Using the River Itchen in southern England as a case study it is shown that the abstraction volume is more sensitive to uncertainty in the regional climate change projection than to the e-flow target. It is also found that "smarter" licensing arrangements (involving a mix of hands off flows and "rising block" abstraction rules) could achieve e-flow targets more frequently than conventional seasonal abstraction limits, with only modest reductions in average annual yield, even under a hotter, drier climate change scenario.

  8. Sensitivity Analysis of OECD Benchmark Tests in BISON

    Energy Technology Data Exchange (ETDEWEB)

    Swiler, Laura Painton [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gamble, Kyle [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmidt, Rodney C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Williamson, Richard [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    This report summarizes a NEAMS (Nuclear Energy Advanced Modeling and Simulation) project focused on sensitivity analysis of a fuels performance benchmark problem. The benchmark problem was defined by the Uncertainty Analysis in Modeling working group of the Nuclear Science Committee, part of the Nuclear Energy Agency of the Organization for Economic Cooperation and Development (OECD ). The benchmark problem involv ed steady - state behavior of a fuel pin in a Pressurized Water Reactor (PWR). The problem was created in the BISON Fuels Performance code. Dakota was used to generate and analyze 300 samples of 17 input parameters defining core boundary conditions, manuf acturing tolerances , and fuel properties. There were 24 responses of interest, including fuel centerline temperatures at a variety of locations and burnup levels, fission gas released, axial elongation of the fuel pin, etc. Pearson and Spearman correlatio n coefficients and Sobol' variance - based indices were used to perform the sensitivity analysis. This report summarizes the process and presents results from this study.

  9. 10 CFR 707.9 - Drug testing as a result of an occurrence.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Drug testing as a result of an occurrence. 707.9 Section... Drug testing as a result of an occurrence. When there is an occurrence which is required to be reported... regulations, it may be necessary to test individuals in testing designated positions, or individuals with...

  10. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Kaufman, N.; Bicher, H.I.; Hetzel, F.W.; Brown, M.

    1981-01-01

    We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO/sup 2/ values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response.

  11. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells.

    Directory of Open Access Journals (Sweden)

    Ayako Nakano

    Full Text Available Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2, KG-1 (ABCB1 and HepG2 cells (ABCB1 and ABCG2. Interestingly, although side population (SP cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells.

  12. Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC.

    Science.gov (United States)

    Zhou, Q; Chen, E; Chen, L; Nong, Y; Cheng, X; He, M; Tang, H

    2014-01-01

    The long-term benefits of antiviral treatment are limited by the resistance of hepatitis B virus (HBV). However, the effect of interferon (IFN)α treatment on drug-resistant HBVs is so far unknown. We, therefore, investigated the effects of IFN-α inducer poly-IC on the replication of HBV mutants resistant to drugs such as lamivudine (LAM), adefovir dipivoxil (ADV) and entecavir (ETV) in mice. HBV DNA and HBV DNA intermediate (RI) were employed as markers of the virus replication and 2',5'-oligoadenylate synthase (OAS) mRNA as a marker of IFN-α/β induction. Poly-IC inhibited wtHBV replication and increased levels of OAS mRNA. Compared to the wt virus, the capacity of virus replication was reduced in most LAMr and ETVr mutants except those with mutations rtM(204V+L180M+V173L), and was similary in the ADVr mutants except rt(A121V+N236T). The virus replication was reduced after poly-IC treatment with LAMr and ADVr mutants similary to the wt virus. In contrast, ETVr mutants were resistant to the poly-IC treatment. In conclusion, the capacity of HBV replication and the sensitivity to IFN therapy are influenced by drug-resistant mutations. The IFN therapy may effectively inhibit HBV replication in particular in patients with LAMr or ADVr mutations but not in patients with ETVr mutations.

  13. Re-sensitizing drug-resistant bacteria to antibiotics by designing Antisense Therapeutics

    Science.gov (United States)

    Courtney, Colleen; Chatterjee, Anushree

    2014-03-01

    ``Super-bugs'' or ``multi-drug resistant organisms'' are a serious international health problem, with devastating consequences to patient health care. The Center for Disease Control has identified antibiotic resistance as one of the world's most pressing public health problems as a significant fraction of bacterial infections contracted are drug resistant. Typically, antibiotic resistance is encoded by ``resistance-genes'' which express proteins that carryout the resistance causing functions inside the bacterium. We present a RNA based therapeutic strategy for designing antimicrobials capable of re-sensitizing resistant bacteria to antibiotics by targeting labile regions of messenger RNAs encoding for resistance-causing proteins. We perform in silico RNA secondary structure modeling to identify labile target regions in an mRNA of interest. A synthetic biology approach is then used to administer antisense nucleic acids to our model system of ampicillin resistant Escherichia coli. Our results show a prolonged lag phase and decrease in viability of drug-resistant E. colitreated with antisense molecules. The antisense strategy can be applied to alter expression of other genes in antibiotic resistance pathways or other pathways of interest.

  14. Diagnostic Plausibility of MTBDRplus and MTBDRsl Line Probe Assays for Rapid Drug Susceptibility Testing of Drug Resistant Mycobacterium tuberculosis Strains in Pakistan

    Directory of Open Access Journals (Sweden)

    Javaid

    2016-06-01

    Full Text Available Background World health organization (WHO recommends the use of line probe assays (LiPAs for rapid drug susceptibility testing (DST. However, only a limited number of studies from Pakistan have documented the performance characteristics of line probe assays in testing multi-drug resistant (MDR strains of Mycobacterium tuberculosis (MTB. Objectives The objective of this work is to evaluate the diagnostic plausibility of the LiPA tests MTBDRplus and MTBDRsl on MDR MTB isolates from Pakistan. Patients and Methods This was a cross-sectional study conducted at the Indus hospital, Karachi. LiPA testing was performed on 196 smear-positive samples using BACTEC MGIT 960 as a gold standard. Results The sensitivity of MTBDRplus for isoniazid and rifampicin was found to be 88.8% and 90.2%, respectively, while sensitivity of MTBDRsl for fluoroquinolones, amikacin/capreomycin, and ethambutol was found to be 72.9%, 81.8%, and 56.6%, respectively. Conclusions The MTBDRplus and MTBDRsl genotypic testing can serve as useful additional tools for DST in a high-burden country like Pakistan provided it is used in combination with phenotypic testing.

  15. Effect In Vitro of Antiparasitic Drugs on Microbial Inhibitor Test Responses for Screening Antibiotic Residues in Goat's Milk.

    Science.gov (United States)

    Romero, T; Beltrán, M C; Reybroeck, W; Molina, M P

    2015-09-01

    Microbial inhibitor tests are widely used to screen antibiotic residues in milk; however, these tests are nonspecific and may be affected by various substances capable of inhibiting the growth of the test microorganism. The objective of this study was to determine the effect of antiparasitic drugs in goat's milk on the microbial inhibitor test response. Raw antibiotic-free milk from Murciano-Granadina goats was supplemented with eight concentrations of seven antiparasitic substances (albendazole, 10 to 170 mg/kg; closantel, 1 to 140 mg/kg; diclazuril, 8 to 45 mg/kg; febendazole, 10 to 140 mg/kg; levamisole, 40 to 440 mg/kg; diazinon, 8 to 45 mg/kg; and ivermectin, 40 to 200 mg/kg). Twelve replicates for each concentration were analyzed with three microbial inhibitor tests: BRT MRL, Delvotest SP-NT MSC, and Eclipse 100. The results were interpreted visually (negative or positive). Using a logistic regression model, the concentrations of the antiparasitic drugs producing 5% (IC5), 10% (IC10), and 50% (IC50) positive results were determined. In general, the Eclipse 100 test was less sensitive to the effect of antiparasitic substances; the inhibitory concentrations of almost all the drugs assayed were higher than those for other tests. Conversely, the BRT MRL test was most affected, with high levels of interference at lower antiparasitic drug concentrations. Closantel and diazinon interfered with all microbial tests at lower concentrations than did other drugs (IC5 = 1 to 26 and 12 to 20 mg/kg, respectively), and higher concentrations of levamisole and diclazuril (IC5 = 30 to 240 and 50 to 117 mg/kg, respectively) were required to produce 5% positive results. These findings indicate that microbial inhibitor tests can be affected by elevated concentrations of antiparasitic drugs in goat's milk.

  16. A microcosting study of immunogenicity and tumour necrosis factor alpha inhibitor drug level tests for therapeutic drug monitoring in clinical practice.

    Science.gov (United States)

    Jani, Meghna; Gavan, Sean; Chinoy, Hector; Dixon, William G; Harrison, Beverley; Moran, Andrew; Barton, Anne; Payne, Katherine

    2016-12-01

    To identify and quantify resource required and associated costs for implementing TNF-α inhibitor (TNFi) drug level and anti-drug antibody (ADAb) tests in UK rheumatology practice. A microcosting study, assuming the UK National Health Service perspective, identified the direct medical costs associated with providing TNFi drug level and ADAb testing in clinical practice. Resource use and costs per patient were identified via four stages: identification of a patient pathway with resource implications; estimation of the resources required; identification of the cost per unit of resource (2015 prices); and calculation of the total costs per patient. Univariate and multiway sensitivity analyses were performed using the variation in resource use and unit costs. Total costs for TNFi drug level and concurrent ADAb testing, assessed using ELISAs on trough serum levels, were £152.52/patient (range: £147.68-159.24) if 40 patient samples were tested simultaneously. For the base-case analysis, the pre-testing phase incurred the highest costs, which included booking an additional appointment to acquire trough blood samples. The additional appointment was the key driver of costs per patient (67% of the total cost), and labour accounted for 10% and consumables 23% of the total costs. Performing ELISAs once per patient (rather than in duplicate) reduced the total costs to £133.78/patient. This microcosting study is the first assessing the cost of TNFi drug level and ADAb testing. The results could be used in subsequent cost-effectiveness analyses of TNFi pharmacological tests to target treatments and inform future policy recommendations. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  17. Trends in reports of driving following illicit drug consumption among regular drug users in Australia, 2007-2013: Has random roadside drug testing had a deterrent effect?

    Science.gov (United States)

    Horyniak, Danielle; Dietze, Paul; Lenton, Simon; Alati, Rosa; Bruno, Raimondo; Matthews, Allison; Breen, Courtney; Burns, Lucy

    2017-07-01

    Driving following illicit drug consumption ('drug-driving') is a potential road safety risk. Roadside drug testing (RDT) is conducted across Australia with the dual aims of prosecuting drivers with drugs in their system and deterring drug-driving. We examined trends over time in self-reported past six-month drug-driving among sentinel samples of regular drug users and assessed the impact of experiences of RDT on drug-driving among these participants. Data from 1913 people who inject drugs (PWID) and 3140 regular psychostimulant users (RPU) who were first-time participants in a series of repeat cross-sectional sentinel studies conducted in Australian capital cities from 2007 to 2013 and reported driving in the past six months were analysed. Trends over time were assessed using the χ(2) test for trend. Multivariable logistic regressions assessed the relationship between experiences of RDT and recent drug-driving, adjusting for survey year, jurisdiction of residence and socio-demographic and drug use characteristics. The percentage of participants reporting recent (past six months) drug-driving decreased significantly over time among both samples (PWID: 83% [2007] vs. 74% [2013], pdrug-driving remained prevalent. Lifetime experience of RDT increased significantly over time (PWID: 6% [2007] vs. 32% [2013], pdrug-driving among either PWID or RPU. Although there is some evidence that drug-driving among key risk groups of regular drug users is declining in Australia, possibly reflecting a general deterrent effect of RDT, experiencing RDT appears to have no specific deterrent effect on drug-driving. Further intervention, with a particular focus on changing attitudes towards drug-driving, may be needed to further reduce this practice among these groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The Effect of MicroRNA-124 Overexpression on Anti-Tumor Drug Sensitivity.

    Directory of Open Access Journals (Sweden)

    Shiau-Mei Chen

    Full Text Available MicroRNAs play critical roles in regulating various physiological processes, including growth and development. Previous studies have shown that microRNA-124 (miR-124 participates not only in regulation of early neurogenesis but also in suppression of tumorigenesis. In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs. We then examined which DNA repair-related genes, particularly the genes of SB repair, were regulated by miR-124. Two SB repair-related genes, encoding ATM interactor (ATMIN and poly (ADP-ribose polymerase 1 (PARP1, were strongly affected by miR-124 overexpression, by binding of miR-124 to the 3¢-untranslated region of their mRNAs. As a result, the capacity of cells to repair DNA SBs, such as those resulting from homologous recombination, was significantly reduced upon miR-124 overexpression. A particularly important therapeutic implication of this finding is that overexpression of miR-124 enhanced cell sensitivity to multiple DNA-damaging agents via ATMIN- and PARP1-mediated mechanisms. The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy. These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.

  19. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

    Directory of Open Access Journals (Sweden)

    Zai-Fa Hong

    Full Text Available Cholangiocarcinoma (CCA, a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K/protein kinase B (AKT/mammalian target of rapamycin (mTOR pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  20. Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

    NARCIS (Netherlands)

    Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

    2014-01-01

    OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

  1. PPO/PEO modified hollow fiber membranes improved sensitivity of 3D cultured hepatocytes to drug toxicity via suppressing drug adsorption on membranes.

    Science.gov (United States)

    Shen, Chong; Meng, Qin; He, Wenjuan; Wang, Qichen; Zhang, Guoliang

    2014-11-01

    The three dimensional (3D) cell culture in polymer-based micro system has become a useful tool for in vitro drug discovery. Among those polymers, polysulfone hollow fiber membrane (PSf HFM) is commonly used to create a microenvironment for cells. However, the target drug may adsorb on the polymeric surface, and this elicits negative impacts on cell exposure due to the reduced effective drug concentration in culture medium. In order to reduce the drug adsorption, PSf membrane were modified with hydrophilic Pluronic (PEO-b-PPO-b-PEO) copolymers, L121, P123 and F127 (PEO contents increase from 10%, 30% to 70%), by physical adsorption. As a result, the hydrophilicity of HFMs increased at an order of PSfF127>P123>L121 HFMs. The three modified membrane all showed significant resistance to adsorption of acid/neutral drugs. More importantly, the adsorption of base drugs were largely reduced to an average value of 11% on the L121 HFM. The improved resistance to drug adsorption could be attributed to the synergy of hydrophobic/neutrally charged PPO and hydrophilic PEO. The L121 HFM was further assessed by evaluating the drug hepatotoxicity in 3D culture of hepatocytes. The base drugs, clozapine and doxorubicin, showed more sensitive hepatotoxicity on hepatocytes in L121 HFM than in PSf HFM, while the acid drug, salicylic acid, showed the similar hepatotoxicity to hepatocytes in both HFMs. Our finding suggests that PSf HFM modified by PEO-b-PPO-b-PEO copolymers can efficiently resist the drug adsorption onto polymer membrane, and consequently improve the accuracy and sensitivity of in vitro hepatotoxic drug screening.

  2. College Athletes and Drug Testing: Attitudes and Behaviors by Gender and Sport

    OpenAIRE

    Schneider, Dona; Morris, Joyce

    1993-01-01

    We surveyed varsity athletes at a Big East university to assess attitudes toward a mandatory drug education and testing program and examined whether there were differences in drug-related attitudes and behaviors based on gender or varsity sport. We found no statistically significant differences in personal drug use behaviors based on gender or team affiliation. Attitudes about drug use and knowledge of a teammate using drugs did show significant differences based on varsity sport. Tennis play...

  3. Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Linh Nguyen

    2017-03-01

    Full Text Available Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets, such as those by Genomics of Drug Sensitivity in Cancer (GDSC consortium, were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than standard k-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug. Regarding overall classification performance, about two thirds of the drugs are better predicted by the multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: Thanks to this unbiased validation, we now know that this type of models can predict in vitro tumour response to some of these

  4. Women's opinions of legal requirements for drug testing in prenatal care.

    Science.gov (United States)

    Tucker Edmonds, Brownsyne; Mckenzie, Fatima; Austgen, MacKenzie B; Carroll, Aaron E; Meslin, Eric M

    2017-07-01

    To explore women's attitudes and perceptions regarding legal requirements for prenatal drug testing. Web-based survey of 500 US women (age 18-45) recruited from a market research survey panel. A 24-item questionnaire assessed their opinion of laws requiring doctors to routinely verbal screen and urine drug test patients during pregnancy; recommendations for consequences for positive drug tests during pregnancy; and opinion of laws requiring routine drug testing of newborns. Additional questions asked participants about the influence of such laws on their own care-seeking behaviors. Data were analyzed for associations between participant characteristics and survey responses using Pearson's chi-squared test. The majority of respondents (86%) stated they would support a law requiring verbal screening of all pregnant patients and 73% would support a law requiring universal urine drug testing in pregnancy. Fewer respondents were willing to support laws that required verbal screening or urine drug testing (68% and 61%, respectively) targeting only Medicaid recipients. Twenty-one percent of respondents indicated they would be offended if their doctors asked them about drug use and 14% indicated that mandatory drug testing would discourage prenatal care attendance. Women would be more supportive of policies requiring universal rather than targeted screening and testing for prenatal drug use. However, a noteworthy proportion of women would be discouraged from attending prenatal care - a reminder that drug testing policies may have detrimental effects on maternal child health.

  5. Test Prioritization based on Change Sensitivity: an Industrial Case Study

    NARCIS (Netherlands)

    Nguyen, Cu; Tonella, Paolo; Vos, Tanja; Condori, Nelly; Mendelson, Bilha; Citron, Daniel; Shehory, Onn

    2014-01-01

    In the context of service-based systems, applications access software services, either home-built or third-party, to orchestrate their functionality. Since such services evolve independently from the applications, the latter need to be tested to make sure that they work properly with the updated or

  6. On the reliability of sensitivity test methods for submicrometer-sized RDX and HMX particles

    NARCIS (Netherlands)

    Radacsi, N.; Bouma, R.H.B.; Krabbendam-La Haye, E.L.M.; Horst, J.H. ter; Stankiewicz, A.I.; Heijden, A.E.D.M. van der

    2013-01-01

    Submicrometer-sized RDX and HMX crystals were produced by electrospray crystallization and submicrometer-sized RDX crystals were produced by plasma-assisted crystallization. Impact and friction sensitivity tests and ballistic impact chamber tests were performed to determine the product sensitivity.

  7. On the reliability of sensitivity test methods for submicrometer-sized RDX and HMX particles

    NARCIS (Netherlands)

    Radacsi, N.; Bouma, R.H.B.; Krabbendam-La Haye, E.L.M.; Horst, J.H. ter; Stankiewicz, A.I.; Heijden, A.E.D.M. van der

    2013-01-01

    Submicrometer-sized RDX and HMX crystals were produced by electrospray crystallization and submicrometer-sized RDX crystals were produced by plasma-assisted crystallization. Impact and friction sensitivity tests and ballistic impact chamber tests were performed to determine the product sensitivity.

  8. Recreational drug use and fluctuating asymmetry: testing the handicap principle.

    Science.gov (United States)

    Borkowska, Barbara; Pawlowski, Boguslaw

    2014-08-26

    Zahavi's handicap principle suggests that only organisms with good genetic quality can afford to engage in costly behaviors. Recreational drug use can be harmful to one's health and therefore might be viewed as a costly signal of one's genetic quality. One of the measurements of genetic quality is bodily symmetry assessed by fluctuating asymmetry. If unhealthy drug use is a behavioral example of Zahavi's handicap principle, then men who use different stimulants or recreational drugs should be more symmetrical than men who do not use them at all or use them only in low quantity. The aim of this study was to examine the relationships between drug use and fluctuating asymmetry. The subjects were 190 young women and 202 young men. Six bilaterally symmetrical traits were measured: length of II-V digits, wrist breadth, and ear height. Questionnaires included questions about smoking, alcohol drinking, drug use, and designer drug use. There was no relationship between bodily symmetry and smoking frequency, alcohol drinking frequency, drug or designer drug use, total substance use, age of smoking initiation, or reason of this initiation. The results indicate that drug use does not reflect genetic quality and does not necessarily relate to the handicap hypothesis.

  9. Frequently Asked Questions about Drug Testing in Schools

    Science.gov (United States)

    ... Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ...

  10. Test-Retest Stability and Concurrent Validity of Two Reading Tests with a Drug-Abusing Population.

    Science.gov (United States)

    Johnson, Mark E.; Fisher, Dennis G.; Rhodes, Fen; Booth, Robert

    1996-01-01

    The Wide Range Achievement Test-Revised and the Woodcock Reading Mastery Tests-Revised were administered twice to 269 current drug abusers over an average time interval of 204.2 days. Overall, the study demonstrates that the two instruments have strong psychometric properties and that results from current drug abusers are reliable. (SLD)

  11. Sensitivity of some asphalts to the wheel tracking test

    OpenAIRE

    Dubois, Vincent; DE LA ROCHE, Chantal; Buisson, Sébastien

    2008-01-01

    In the framework of LCPC fatigue carrousel studies [Corté and others, 1994; Gramsammer and others, 1994], rutting measurements on several mixes have been carried out. For each mix, the granular distribution has been identical, but different types of bitumen have been chosen : classical bitumen 50/70, EVA modified bitumen and SBS modified bitumen. These mixes have been designed by a previous laboratory tests campaign. In comparing field and laboratory results, a different behaviour is observed...

  12. Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery.

    Science.gov (United States)

    Du, Jin-Zhi; Du, Xiao-Jiao; Mao, Cheng-Qiong; Wang, Jun

    2011-11-09

    Efficient delivery of therapeutics into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to drug resistance and inefficient cellular uptake. Herein, we have designed a tailor-made dual pH-sensitive polymer-drug conjugate nanoparticulate system to overcome the challenges. The nanoparticle is capable of reversing its surface charge from negative to positive at tumor extracellular pH (∼6.8) to facilitate cell internalization. Subsequently, the significantly increased acidity in subcellular compartments such as the endosome (∼5.0) further promotes doxorubicin release from the endocytosed drug carriers. This dual pH-sensitive nanoparticle has showed enhanced cytotoxicity in drug-resistant cancer stem cells, indicating its great potential for cancer therapy.

  13. A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Noushin Davoudi

    Full Text Available Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine is available against any form of the disease. Historically, leishmanization (LZ which is an inoculation of individual with live Leishmania, is the most effective control measure at least against cutaneous leishmaniasis (CL. Due to various reasons, LZ is not used today. Several live attenuated Leishmania have been developed but their use is limited. Previously, we developed a transgenic strain of L. major that harbors two suicide genes tk and cd genes (lmtkcd+/+ for use as a challenge strain in vaccine studies. These genes render the parasite susceptible to Ganciclovir (GCV and 5-flurocytosine (5-FC. The dual drug sensitive strain of L. major was developed using gene targeting technology using a modified Herpes Simplex Virus thymidine kinase gene (hsv-tk sensitive to Ganciclovir antibiotic and Saccharomyces cerevisae cytosine deaminase gene (cd sensitive to 5-flurocytosine that were stably introduced into L. major chromosome. BALB/c mice inoculated with lmtkcd+/+ developed lesions which upon treatment with GCV and 5-FC completely healed. In the current study, the transgenic lmtkcd+/+strain was assessed as a live vaccine model to determine the time necessary to develop a protective immune response. C57BL/6 mice were inoculated with the transgenic lmtkcd+/+strain, and treated at the time of inoculation (day 0 or at day 8 after inoculation. Immunized animals were challenged with wild-type L. major, and complete protection was induced in mice that were treated at day 8. The results show that in contrast to leishmanization, in group of mice inoculated with a dual sensitive L. major development and persistence of lesion is not necessary to induce Th1 response and protection.

  14. Spectrofluorimetric determination of certain adrenergic agonist drugs in their pure forms and pharmaceutical formulations: Content uniformity test application.

    Science.gov (United States)

    Badr El-Din, Khalid M; Attia, Tamer Z

    2016-11-29

    A new, simple, sensitive and rapid spectrofluorimetric method has been developed for determination of certain adrenergic agonists such as isoxsuprine hydrochloride, ritodrine hydrochloride and etilefrine hydrochloride in their pure forms and pharmaceutical dosage forms. The method depends on micellar enhancement of the native fluorescence of investigated drugs by using 2% w/v sodium dodecyl sulfate (SDS) as an anionic surfactant. The enhanced fluorescence intensity of investigated drugs was measured at 305 nm after excitation at 278 nm. The interaction of studied drugs with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of investigated drugs. The relative fluorescence intensity-concentration plots were rectilinear over the range 0.15-3.00 μg ml(-1) , with low quantification limits of 0.132, 0.123 and 0.118 μg mL(-1) for isoxsuprine, ritodrine and etilefrine, respectively. The proposed method was successfully applied for determination of studied drugs in their pharmaceutical formulations. Moreover, the high sensitivity of the proposed method allows performing the content uniformity testing of the studied drugs in their tablets by using the official United States Pharmacopeia (USP) guidelines. Statistical comparisons of the results with those of the reported methods revealed excellent agreement and indicated no significant difference in accuracy and precision.

  15. Seven years of workplace drug testing in Italy: A systematic review and meta-analysis.

    Science.gov (United States)

    Rosso, Gian Luca; Montomoli, Cristina; Morini, Luca; Candura, Stefano M

    2017-06-01

    In Italy, Workplace Drug Testing (WDT) has been compulsory by law for specific categories of workers since 2008, offering the opportunity to compare studies conducted within a single regulatory framework. The aims of this paper are to estimate the overall prevalence of WDT positivity (at screening survey) among Italian workers and evaluate the percentage of true and false positives at confirmation analysis. A systematic review and meta-analysis of the scientific literature on WDT in Italy from January 2008 to March 2015 was carried out, according to the MOOSE guidelines. A random effects model was utilized to calculate pooled prevalence. Potential sources of heterogeneity were explored using sensitivity test and subgroup analysis. The overall meta-analytical prevalence of positivity at WDT among Italian workers was 1.4% [95% confidence interval (CI) = 1.1-1.7%]. It was significantly lower among workers screened with an on-site test (1%; 95% CI = 0.5-1.5%), compared with a bench-top test (1.7%; 95% CI = 1.3-2.1%). Nine studies provided data on false positives at the screening test, with a combined prevalence estimate - calculated on positive cases - of 30% (95% CI = 16-44%). In Italy, the number of true positives at first-level workplace drug testing is low, while the frequency of false positives is relatively high. A revision of the Italian legislation on the subject seems advisable. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Personalized Medicine : Pharmacogenetic Testing in Drug Development and Clinical Practice

    NARCIS (Netherlands)

    van der Baan, F.H.

    2012-01-01

    For drugs that are registered on the market, efficacy was proven on a population level. However, on an individual level, most drugs have a different effect in different patients. They may fail to work in some patients or cause serious side effects. Pharmacogenetic research studies the contribution o

  17. NEW ANTIMICROBIAL SENSITIVITY TESTS OF BIOFILM OF STREPTOCOCCUS MUTANS IN ARTIFICIAL MOUTH MODEL

    Institute of Scientific and Technical Information of China (English)

    李鸣宇; 汪俊; 刘正; 朱彩莲

    2004-01-01

    Objective To develop a new antimicrobial sensitivity test model for oral products in vitro.Methods A biofilm artificial mouth model for antimicrobial sensitivity tests was established by modifying the LKI chromatography chamber. Using sodium fluoride and Tea polyphenol as antimicrobial agent and Streptococcus mutans as target, sensitivity tests were studied. Results The modeling biofilm assay resulted in a MIC of 1.28mg/ml for fluoride against S. mutans, which was 32 times the MIC for broth maco-dilution method. The differential resistance of bacteria bioflim to antimicrobial agent relative to planktonic cells was also demonstrated. Conclusion The biofilm artificial mouth model may be useful in oral products test.

  18. Sense and sensitivity: physical limits to multicellular sensing and drug response

    CERN Document Server

    Varennes, Julien

    2015-01-01

    Metastasis is a process of cell migration that can be collective and guided by chemical cues. Viewing metastasis in this way, as a physical phenomenon, allows one to draw upon insights from other studies of collective sensing and migration in cell biology. Here we review recent progress in the study of cell sensing and migration as collective phenomena, including in the context of metastatic cells. We describe simple physical models of sensing and migration, and we survey the experimental evidence that cells operate near the purely physical limits to their behavior. We conclude by contrasting cells' sensory abilities with their sensitivity to drugs, and suggesting potential alternatives to cell-death-based cancer therapies.

  19. 10 CFR 707.12 - Specimen collection, handling and laboratory analysis for drug testing.

    Science.gov (United States)

    2010-01-01

    ... drug testing. 707.12 Section 707.12 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.12 Specimen collection, handling and laboratory analysis for drug testing... collection to final disposition of specimens, and testing laboratories shall use appropriate cutoff levels in...

  20. Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.

    Science.gov (United States)

    Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

    2015-04-02

    Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.

  1. SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets.

    Science.gov (United States)

    Guo, Jing; Liu, Hui; Zheng, Jie

    2016-01-04

    Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference between cancer cells and normal cells, and thus the inhibition of SL partners of genes with cancer-specific mutations could selectively kill cancer cells but spare normal cells. Therefore, SL is emerging as a promising anticancer strategy that could potentially overcome the drawbacks of traditional chemotherapies by reducing severe side effects. Researchers have developed experimental technologies and computational prediction methods to identify SL gene pairs on human and a few model species. However, there has not been a comprehensive database dedicated to collecting SL pairs and related knowledge. In this paper, we propose a comprehensive database, SynLethDB (http://histone.sce.ntu.edu.sg/SynLethDB/), which contains SL pairs collected from biochemical assays, other related databases, computational predictions and text mining results on human and four model species, i.e. mouse, fruit fly, worm and yeast. For each SL pair, a confidence score was calculated by integrating individual scores derived from different evidence sources. We also developed a statistical analysis module to estimate the druggability and sensitivity of cancer cells upon drug treatments targeting human SL partners, based on large-scale genomic data, gene expression profiles and drug sensitivity profiles on more than 1000 cancer cell lines. To help users access and mine the wealth of the data, we developed other practical functionalities, such as search and filtering, orthology search, gene set enrichment analysis. Furthermore, a user-friendly web interface has been implemented to facilitate data analysis and interpretation. With the integrated data sets and analytics functionalities, SynLethDB would

  2. Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs

    Science.gov (United States)

    Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

    2015-01-01

    Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors. PMID:25837486

  3. Microflora of conjunctiva in children and its sensitivity and resistance to antibacterial drugs

    Directory of Open Access Journals (Sweden)

    T. N. Vorontsova

    2012-01-01

    Full Text Available Purpose: Investigation of microflora of conjunctiva and its resistance to antibacterial drugs in healthy children and patients with various inflammatory eye diseases.Methods: We examined 402 children (421 eyes in the age from 1 month till 17 years: 62 healthy children (70 eyes and 340 pa- tients with different inflammatory diseases of anterior segment of eye (351 eyes. the smear was done in all children for plating and definition of sensitivity of microflora to antibacterial drugs by method of diffusion to agar.Results: the plating was positive even in 72.9% of healthy children who entered the hospital for the planned surgery. Most often we revealed Staphylococcus epidermidis (44.3%, Staphylococcus aureus (12.8%, Streptococcus faecalis (5.7% and Enterobacter (2.9%. In children with inflammatory diseases Staphylococcus epidermidis and Staphylococcus aureus (62.6% were found fre- quently. the analysis of data showed high level of resistance of all microflora to aminoglycosides (neomycin 37.8% and tobramycin 32.7% and chloramphenicol — 37.1%. the lowest resistance of all microflora was registered to levofloxacin (11.1% and ciprofloxacin (10.5%. In gram-negative microflora we revealed the maximal sensitivity to ciprofloxacin, in gram-positive — to levofloxacin.We detected the maximal resistance of microflora to ampicillin (66.1%, and minimal — to cephalosporines (4.5% among the antibiotics of systemic application.Conclusion: the findings allow us to recommend drops containing levofloxacin (Signicef for clinical practice in pediatric ophthalmology. 

  4. The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

    Directory of Open Access Journals (Sweden)

    Malcolm J. Reid

    2011-12-01

    Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

  5. Thermo-sensitive liposomes loaded with doxorubicin and lysine modified single-walled carbon nanotubes as tumor-targeting drug delivery system.

    Science.gov (United States)

    Zhu, Xiali; Xie, Yingxia; Zhang, Yingjie; Huang, Heqing; Huang, Shengnan; Hou, Lin; Zhang, Huijuan; Li, Zhi; Shi, Jinjin; Zhang, Zhenzhong

    2014-11-01

    This report focuses on the thermo-sensitive liposomes loaded with doxorubicin and lysine-modified single-walled carbon nanotube drug delivery system, which was designed to enhance the anti-tumor effect and reduce the side effects of doxorubicin. Doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes was prepared by reverse-phase evaporation method, the mean particle size was 232.0 ± 5.6 nm, and drug entrapment efficiency was 86.5 ± 3.7%. The drug release test showed that doxorubicin released more quickly at 42℃ than at 37℃. Compared with free doxorubicin, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes could efficiently cross the cell membranes and afford higher anti-tumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) cells in vitro. For in vivo experiments, the relative tumor volumes of the sarcomaia 180-bearing mice in thermo-sensitive liposomes group and doxorubicin group were significantly smaller than those of N.S. group. Meanwhile, the combination of near-infrared laser irradiation at 808 nm significantly enhanced the tumor growth inhibition both on SMMC-7721 cells and the sarcomaia 180-bearing mice. The quality of life such as body weight, mental state, food and water intake of sarcomaia 180 tumor-bearing mice treated with doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes were much higher than those treated with doxorubicin. In conclusion, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes combined with near-infrared laser irradiation at 808 nm may potentially provide viable clinical strategies for targeting delivery of anti-cancer drugs.

  6. Sensitivity and specificity of nested PCR pyrosequencing in hepatitis B virus drug resistance gene testing%巢式PCR联合焦磷酸测序法在乙型肝炎病毒耐药基因检测中的敏感性与特异性分析

    Institute of Scientific and Technical Information of China (English)

    孙树梅; 周浩; 周彬; 胡子有; 侯金林; 孙剑

    2012-01-01

    Objective To evaluate the sensitivity and specificity of nested PCR combined with pyrosequenring in the detection of HBV drug-resistance gene.Methods RtM2041 (ATT) mutant and rtM204 (ATG) nonmutant plasmids mixed at different ratios were detected for mutations using nested-PCR combined with pyrosequenring,and the results were compared with those by conventional PCR pyrosequencing to analyze the linearity and consistency of the two methods.Clinical specimens with different viral loads were examined for drug-resistant mutations using nested PCR pyrosequencing and nested PCR combined with dideoxy sequencing (Sanger) for comparison of the detection sensitivity and specificity.Results The fitting curves demonstrated good linearity of both conventional PCR pyrosequencing and nested PCR pyrosequencing (R2>0.99,P< 0.05).Nested PCR showed a better consistency with the predicted value than conventional PCR,and was superior to conventional PCR for detection of samples containing 90% mutant plasmid.In the detection of clinical specimens,Sanger sequencing had a significantly lower sensitivity than nested PCR pyrosequencing (92% vs 100%,P<0.01).The detection sensitivity of Sanger sequencing varied with the viral loads,especially in samples with low viral copies (HBV DNA≤3logl0 copies/ml),where the sensitivity was 78%,significantly lower than that of pyrosequencing (100%,P<0.01).Neither of the two methods yielded positive results for the negative control samples,suggesting their good specificity.Conclusion Compared with nested PCR and Sanger sequencing method,nested PCR pyrosequencing has a higher sensitivity especially in clinical specimens with low viral copies,which can be important for early detection of HBV mutant strains and hence more effective clinical management.%目的 评价巢式PCR联合焦磷酸测序法在乙型肝炎病毒(HBV)耐药基因检测中的敏感与特异性.方法 选取rtM204I(ATT)突变型和rtM204(ATG)未突变型质粒,按照不同比例混合

  7. Development of pH-sensitive pectinate/alginate microspheres for colon drug delivery.

    Science.gov (United States)

    Hsu, Fu-Yin; Yu, Ding-Syuan; Huang, Chun-Chiang

    2013-02-01

    The purposes of this study were to develop and evaluate calcium pectinate/alginate microspheres (PAMs) and to exploit their pH-sensitive properties for colon-targeted delivery of encapsulated cisplatin. PAMs were prepared using an electrospraying method. The PAMs, as cores, were then coated with Eudragit S100 using a polyelectrolyte multilayer coating technique in aqueous solution. The morphology of the microspheres was observed under scanning electron microscopy. In vitro drug release studies were performed in simulated gastrointestinal fluid, and the results indicated that approximately 5 % of the cisplatin was released from the Eudragit S100-coated PAMs, and 51 % of the cisplatin was released from the uncoated PAMs at 1 h. The release of cisplatin from the Eudragit S100-coated PAMs was more sustained in simulated gastric fluid than in simulated intestinal fluid due to the increased solubility of the coating polymer in media with pH >7.0. Drug release from the Eudragit S100-coated PAMs was best described by the Higuchi's square root model. From these results, it was concluded that Eudragit S100-coated PAMs are a potential carrier for delivery of cisplatin to the colon.

  8. Simple and sensitive method for monitoring drug-induced cell injury in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Shirhatti, V.; Krishna, G.

    1985-06-01

    A simple, sensitive method has been developed for evaluating cell injury noninvasively in monolayer cells in culture. The cell ATP pool was radiolabeled by incubating the cells with (/sup 14/C)adenine. The uptake and incorporation of (/sup 14/C)adenine was shown to proportional to the number of cells. As determined by HPLC, about 65-70% of the incorporated /sup 14/C label was in the ATP pool, 15-20% was in the ADP pool, and the rest was in the 5'-AMP pool. When prelabeled cells were exposed to toxic drugs (acetaminophen, calcium ionophore A-23187, or daunomycin) there was a marked decrease in cell ATP with a concomitant increase in leakage of labeled nucleotides, mainly 5'-AMP and 5'IMP. The authors have shown that leakage of /sup 14/C label into the medium from the prelabeled cells may be employed for quantitation of cell injury. This new measure of toxicity was shown to correlate very well with LDH leakage from the cells, which is a well accepted measure of cell injury. The leakage of 5'-(/sup 14/C)AMP also correlated very well with the reduction of cell ATP in cardiac myocytes. This method has been used for monitoring drug-induced toxicity in liver cells, cardiac myocytes, and LB cells.

  9. Highly sensitive quantitative imaging for monitoring single cancer cell growth kinetics and drug response.

    Directory of Open Access Journals (Sweden)

    Mustafa Mir

    Full Text Available The detection and treatment of cancer has advanced significantly in the past several decades, with important improvements in our understanding of the fundamental molecular and genetic basis of the disease. Despite these advancements, drug-screening methodologies have remained essentially unchanged since the introduction of the in vitro human cell line screen in 1990. Although the existing methods provide information on the overall effects of compounds on cell viability, they are restricted by bulk measurements, large sample sizes, and lack capability to measure proliferation kinetics at the individual cell level. To truly understand the nature of cancer cell proliferation and to develop personalized adjuvant therapies, there is a need for new methodologies that provide quantitative information to monitor the effect of drugs on cell growth as well as morphological and phenotypic changes at the single cell level. Here we show that a quantitative phase imaging modality known as spatial light interference microscopy (SLIM addresses these needs and provides additional advantages over existing proliferation assays. We demonstrate these capabilities through measurements on the effects of the hormone estradiol and the antiestrogen ICI182,780 (Faslodex on the growth of MCF-7 breast cancer cells. Along with providing information on changes in the overall growth, SLIM provides additional biologically relevant information. For example, we find that exposure to estradiol results in rapidly growing cells with lower dry mass than the control population. Subsequently blocking the estrogen receptor with ICI results in slower growing cells, with lower dry masses than the control. This ability to measure changes in growth kinetics in response to environmental conditions provides new insight on growth regulation mechanisms. Our results establish the capabilities of SLIM as an advanced drug screening technology that provides information on changes in proliferation

  10. Hollow fiber based quantum cascade laser spectrometer for fast and sensitive drug identification

    Science.gov (United States)

    Herbst, J.; Scherer, B.; Ruf, A.; Erb, J.; Lambrecht, A.

    2012-01-01

    Sensitive and fast identification of drugs or drug precursors is important and necessary in scenarios like baggage or container check by customs or police. Fraunhofer IPM is developing a laser spectrometer using external cavity quantum cascade lasers (EC-QCL) to obtain mid-infrared (IR) absorption spectra in the wavelength range of the specific vibrational bands of amphetamines and their precursors. The commercial EC-QCL covers a tuning range of about 225 cm-1 within 1.4 s. The system could be used for different sample types like bulk samples or liquid solutions. A sampling unit evaporates the sample. Because of small sample amounts a 3 m long hollow fiber with an inner volume smaller than 1ml is used as gas cell and wave guide for the laser beam. This setup is suitable as a detector of a gas chromatograph instead of a standard detector (TCD or FID). The advantage is the selective identification of drugs by their IR spectra in addition to the retention time in the gas chromatographic column. In comparison to Fourier Transform IR systems the EC-QCL setup shows a good mechanical robustness and has the advantage of a point light source. Because of the good fiber incoupling performance of the EC-QCL it is possible to use hollow fibers. So, a good absorption signal is achieved because of the long optical path in the small cell volume without significant dilution. In first laboratory experiments a detection limit in the microgram range for pseudo ephedrine is achieved.

  11. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    OpenAIRE

    Kennard, John A.; Woodruff-Pak, Diana S.

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memo...

  12. Sensitization capacity of acrylated prepolymers in ultraviolet curing inks tested in the guinea pig.

    Science.gov (United States)

    Björkner, B

    1981-01-01

    One commonly used prepolymer in ultraviolet (UV) curing inks is epoxy acrylate. Of 6 men with dermatitis contracted from UV-curing inks, 2 had positive patch test reaction to epoxy acrylate. None reacted to the chemically related bisphenol A dimethacrylate. The sensitization capacity of epoxy acrylate and bisphenol A dimethacrylate performed with the "Guinea pig maximization test" (GPM) shows epoxy acrylate to be an extreme sensitizer and bisphenol A dimethacrylate a moderate sensitizer. Cross-reaction between the two substances occurs. The epoxy resin oligomer MW 340 present in the epoxy acrylate also sensitized some animals.

  13. Semiempirical Rules To Determine Drug Sensitivity and Ionization Efficiency in Secondary Ion Mass Spectrometry Using a Model Tissue Sample.

    Science.gov (United States)

    Vorng, Jean-Luc; Kotowska, Anna M; Passarelli, Melissa K; West, Andrew; Marshall, Peter S; Havelund, Rasmus; Seah, Martin P; Dollery, Colin T; Rakowska, Paulina D; Gilmore, Ian S

    2016-11-15

    There is an increasing need in the pharmaceutical industry to reduce drug failure at late stage and thus reduce the cost of developing a new medicine. Since most drug targets are intracellular, this requires a better understanding of the drug disposition within a cell. Secondary ion mass spectrometry has been identified as a potentially important technique to do this, as it is label-free and allows imaging in 3D with subcellular resolution and recent studies have shown promise for amiodarone. An important analytical parameter is sensitivity, and we measure this in a bovine liver homogenate reference sample for 20 drugs representing important class types relevant to the pharmaceutical industry. We also measure the sensitivity for pure drug and show, for the first time, that the secondary ion mass spectrometry (SIMS) positive ionization efficiency for small molecules is a simple power-law relationship to the log P value. This discovery will be important for advancing the understanding of the SIMS ionization process in small molecules that has, until now, been elusive. This simple relationship is found to hold true for drug doped in the bovine liver homogenate reference sample, except for fluticasone, nicardipine, and sorafenib which suffer from severe matrix suppression. This relationship provides a simple semiempirical method to determine drug sensitivity for positive secondary ions. Furthermore, we show, on chosen models, how the use of different solvents during sample preparation can affect the ionization of analytes.

  14. Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Paula I. Moreira

    2009-12-01

    Full Text Available Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ. Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer´s, Parkinson´s and Huntington´s diseases and amyotrophic lateral sclerosis will be also discussed.

  15. The Role of More Sensitive Helminth Diagnostics in Mass Drug Administration Campaigns: Elimination and Health Impacts.

    Science.gov (United States)

    Medley, G F; Turner, H C; Baggaley, R F; Holland, C; Hollingsworth, T D

    2016-01-01

    Diagnostics play a crucial role in determining treatment protocols and evaluating success of mass drug administration (MDA) programmes used to control soil-transmitted helminths (STHs). The current diagnostic, Kato-Katz, relies on inexpensive, reusable materials and can be used in the field, but only trained microscopists can read slides. This diagnostic always underestimates the true prevalence of infection, and the accuracy worsens as the true prevalence falls. We investigate how more sensitive diagnostics would impact on the management and life cycle of MDA programmes, including number of mass treatment rounds, health impact, number of unnecessary treatments and probability of elimination. We use an individual-based model of STH transmission within the current World Health Organization (WHO) treatment guidelines which records individual disability-adjusted life years (DALY) lost. We focus on Ascaris lumbricoides due to the availability of high-quality data on existing diagnostics. We show that the effect of improving the sensitivity of diagnostics is principally determined by the precontrol prevalence in the community. Communities at low true prevalence (70%) do not benefit greatly from improved diagnostics. Communities with intermediate prevalence benefit greatly from increased chemotherapy application, both in terms of reduced DALY loss and increased probability of elimination. Our results suggest that programmes should be extended beyond school-age children, especially in high prevalence communities. Finally, we argue against using apparent or measured prevalence as an uncorrected proxy for true prevalence.

  16. Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe.

    Directory of Open Access Journals (Sweden)

    Victoria L Demetriou

    Full Text Available BACKGROUND: HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC have a predictive value for disease progression, independently of CD4 counts and plasma viral load. METHODOLOGY/PRINCIPAL FINDINGS: Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log(10 HIV-1 copies/10(6 PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4(+ T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. CONCLUSIONS/SIGNIFICANCE: An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA

  17. FDA, companies test RFID tracking to prevent drug counterfeiting.

    Science.gov (United States)

    James, John S

    2005-12-01

    The U.S. has an apparently growing problem with fake, counterfeit drugs entering the mainstream drug supply, and being fraudulently sold at full price in regular pharmacies and hospitals; some have no active ingredient, or too little, or substitute a cheap drug for an expensive one. The FDA has asked drug manufacturers to develop technology to track all shipments electronically as they move through the distribution chain; currently, RFID (radio frequency identification) is the preferred method for doing so. This article explains what is happening, and why we do not believe that this use of RFID is a privacy threat--though other privacy issues are among the most important questions we face today.

  18. Sensitivity and specificity of point-of-care rapid combination syphilis-HIV-HCV tests.

    Directory of Open Access Journals (Sweden)

    Kristen L Hess

    Full Text Available New rapid point-of-care (POC tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California.Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA, rapid plasma reagin (RPR, HCV enzyme immunoassay (EIA, and HIV-1/2 EIA.A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥ 1 ∶ 8.The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.

  19. Novel pH-sensitive IPNs of polyacrylamide-g-gum ghatti and sodium alginate for gastro-protective drug delivery.

    Science.gov (United States)

    Boppana, Rashmi; Krishna Mohan, G; Nayak, Usha; Mutalik, Srinivas; Sa, Biswanath; Kulkarni, Raghavendra V

    2015-04-01

    This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca(2+) ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen.

  20. Student drug testing and positive school climates: testing the relation between two school characteristics and drug use behavior in a longitudinal study.

    Science.gov (United States)

    Sznitman, Sharon R; Romer, Daniel

    2014-01-01

    Fostering positive school climates and student drug testing have been separately proposed as strategies to reduce student drug use in high schools. To assess the promise of these strategies, the present research examined whether positive school climates and/or student drug testing successfully predicted changes in youth substance use over a 1-year follow-up. Two waves of panel data from a sample of 361 high school students, assessed 1 year apart, were analyzed. Changes in reported initiation and escalation in frequency of alcohol, cigarette, and marijuana use as a function of perceived student drug testing and positive school climates were analyzed, while we held constant prior substance use. Perceived student drug testing was not associated with changes in substance use, whereas perceived positive school climates were associated with a reduction in cigarette and marijuana initiation and a reduction in escalation of frequency of cigarette use at 1-year follow-up. However, perceived positive school climates were not associated with a reduction in alcohol use. Student drug testing appears to be less associated with substance use than positive school climates. Nevertheless, even favorable school climates may not be able to influence the use of alcohol, which appears to be quite normative in this age group.

  1. The role of urine drug testing for patients on opioid therapy.

    Science.gov (United States)

    Pergolizzi, Joseph; Pappagallo, Macro; Stauffer, Joseph; Gharibo, Christopher; Fortner, Neil; De Jesus, Mathew N; Brennan, Michael J; Richmond, Charlotte; Hussey, Desmond

    2010-01-01

    Opioid analgesics must be prescribed with discernment and their appropriate use should be periodically assessed. Urine drug testing, although not designed specifically for this role, is a widely available and familiar method for monitoring opioid use in chronic pain patients. Urine drug testing can help track patient compliance and expose possible drug misuse and abuse. We sought to evaluate current attitudes and practices regarding the use of urine drug testing among chronic pain patients taking opioids. To the best of our knowledge, this is one of the first such attempts in the literature to examine and document the practice patterns of urine drug testing in this context. A total of 99 attendees at the American Congress of Pain Medicine were surveyed in 2008 about their urine testing practices for patients on opioid therapy. Surprisingly, more urine testing was motivated by a desire to detect undisclosed substances than to evaluate appropriate opioid use. Some respondents never urine-tested their opioid patients, and about two-thirds of respondents had no formal training in urine testing of patients on opioid therapy. The literature does not thoroughly address the role of urine drug testing in this patient population. Most respondents did random rather than scheduled testing; few had any urine testing protocol. The study found motivations for urine testing and testing practices varied widely, and urine testing, despite its clinical utility, is not used consistently. © 2010 The Authors. Pain Practice © 2010 World Institute of Pain.

  2. Improved sensitivity testing of explosives using transformed Up-Down methods

    Science.gov (United States)

    Brown, Geoffrey W.

    2014-05-01

    Sensitivity tests provide data that help establish guidelines for the safe handling of explosives. Any sensitivity test is based on assumptions to simplify the method or reduce the number of individual sample evaluations. Two common assumptions that are not typically checked after testing are 1) explosive response follows a normal distribution as a function of the applied stimulus levels and 2) the chosen test level spacing is close to the standard deviation of the explosive response function (for Bruceton Up-Down testing for example). These assumptions and other limitations of traditional explosive sensitivity testing can be addressed using Transformed Up-Down (TUD) test methods. TUD methods have been developed extensively for psychometric testing over the past 50 years and generally use multiple tests at a given level to determine how to adjust the applied stimulus. In the context of explosive sensitivity we can use TUD methods that concentrate testing around useful probability levels. Here, these methods are explained and compared to Bruceton Up-Down testing using computer simulation. The results show that the TUD methods are more useful for many cases but that they do require more tests as a consequence. For non-normal distributions, however, the TUD methods may be the only accurate assessment method.

  3. Parametric Sensitivity Tests—European Polymer Electrolyte Membrane Fuel Cell Stack Test Procedures

    DEFF Research Database (Denmark)

    Araya, Samuel Simon; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2014-01-01

    As fuel cells are increasingly commercialized for various applications, harmonized and industry-relevant test procedures are necessary to benchmark tests and to ensure comparability of stack performance results from different parties. This paper reports the results of parametric sensitivity tests...

  4. High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs.

    Science.gov (United States)

    D'Angelo, Daniela; Mussnich, Paula; Rosa, Roberta; Bianco, Roberto; Tortora, Giampaolo; Fusco, Alfredo

    2014-11-20

    Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcinoma cells through an Akt-dependent mechanism. To elucidate the role of HMGA1 proteins in chemoresistance we analyzed resistance to conventional drugs and targeted therapies of human colon carcinoma cells (GEO) that are sensitive to the epidermal growth factor receptor inhibitor cetuximab, and express minimal levels of HMGA1 and cetuximab-resistant (GEO CR) cells expressing high HMGA1 protein levels. GEO CR cells were less sensitive than GEO cells to cetuximab and 5-fluorouracil. GEO CR cells silenced for HMGA1 expression were more susceptible than empty vector-transfected cells to the drugs' cytotoxicity. Similar results were obtained with anaplastic thyroid carcinoma cells expressing or not HMGA1 proteins, treated with doxorubicin or the HDAC inhibitor LBH589. Finally, HMGA1 overexpression promoted the DNA-damage response and stimulated Akt phosphorylation and prosurvival signaling. Our findings suggest that the blockage of HMGA1 expression is a promising approach to enhance cancer cell chemosensitivity, since it could increase the sensitivity of cancer cells to antineoplastic drugs by inhibiting the survival signal and DNA damage repair pathways.

  5. Novel multifunctional pH-sensitive nanoparticles loaded into microbubbles as drug delivery vehicles for enhanced tumor targeting.

    Science.gov (United States)

    Lv, Yongjiu; Hao, Lan; Hu, Wenjing; Ran, Ya; Bai, Yan; Zhang, Liangke

    2016-01-01

    This study fabricated novel multifunctional pH-sensitive nanoparticles loaded into microbubbles (PNP-MB) with the combined advantages of two excellent drug delivery vehicles, namely, pH-sensitive nanoparticles and microbubbles. As an antitumor drug, resveratrol (RES) was loaded into acetylated β-cyclodextrin nanoparticles (RES-PNP). The drug-loaded nanoparticles were then encapsulated into the internal space of the microbubbles. The characterization and morphology of this vehicle were investigated through dynamic light scattering and confocal laser scanning microscopy, respectively. In vitro drug release was performed to investigate the pH sensitivity of RES-PNP. The antitumor property of RES-loaded PNP-MB (RES-PNP-MB) was also analyzed in vivo to evaluate the antitumor effect of RES-PNP-MB. Results suggested that PNP exhibited pH sensitivity, and was successfully encapsulated into the microbubbles. RES-PNP-MB exhibit effective tumor growth suppressing in vivo. Therefore, such drug delivery vehicle should be of great attention in tumor therapy.

  6. 75 FR 35712 - National Pollutant Discharge Elimination System (NPDES): Use of Sufficiently Sensitive Test...

    Science.gov (United States)

    2010-06-23

    ... sensitive'' analytical methods with respect to measurement of mercury and extend the approach outlined in...): Use of Sufficiently Sensitive Test Methods for Permit Applications and Reporting AGENCY: Environmental... methods can be used when completing an NPDES permit application and when performing sampling and...

  7. Forensic Toxicology Program: alcohol and drug testing in Wisconsin drivers.

    Science.gov (United States)

    Harding, Patrick; Liddicoat, Laura J

    2003-01-01

    The Forensic Toxicology Program of the Wisconsin State Laboratory of Hygiene (WSLH) provides analytical and support services to assist in the identification of alcohol- and/or drug-impaired drivers and to assist in determining cause of death. These services are provided to law enforcement agencies, the Wisconsin Department of Natural Resources, the Wisconsin Department of Transportation, and county medical examiners and coroners. Program staff is active in alcohol and drug training, policy-making, and research on a national and international level.

  8. Integrating non-animal test information into an adaptive testing strategy - skin sensitization proof of concept case.

    Science.gov (United States)

    Jaworska, Joanna; Harol, Artsiom; Kern, Petra S; Gerberick, G Frank

    2011-01-01

    There is an urgent need to develop data integration and testing strategy frameworks allowing interpretation of results from animal alternative test batteries. To this end, we developed a Bayesian Network Integrated Testing Strategy (BN ITS) with the goal to estimate skin sensitization hazard as a test case of previously developed concepts (Jaworska et al., 2010). The BN ITS combines in silico, in chemico, and in vitro data related to skin penetration, peptide reactivity, and dendritic cell activation, and guides testing strategy by Value of Information (VoI). The approach offers novel insights into testing strategies: there is no one best testing strategy, but the optimal sequence of tests depends on information at hand, and is chemical-specific. Thus, a single generic set of tests as a replacement strategy is unlikely to be most effective. BN ITS offers the possibility of evaluating the impact of generating additional data on the target information uncertainty reduction before testing is commenced.

  9. Urine drug testing for social service agencies in Nova Scotia, Canada.

    Science.gov (United States)

    Fraser, A D

    1998-01-01

    In Nova Scotia Canada, governmental authorities expressed concern in the late 1980s about the adverse effects of drug use by parents on the welfare of their children. Since 1991, parents with a history of drug abuse may be required to submit to urine drug and alcohol testing when ordered by the Family Courts of this province. The objective of this paper is to present this drug testing program and the results of drug testing on 125 clients from 1994-1996. Urine specimens were collected in the parents' residence by a nurse and transferred directly to the laboratory by the collector or a courier. Specimens were screened by immunoassay and TLC followed by GC-MS confirmation. Results were sent directly to the social worker. In the 3,613 urine specimens analyzed, 50.2% of specimens were negative, 45.6% were positive for one or more drug/metabolite and 4.2% of specimens were dilute (creatinine Drug testing has been considered a success by these agencies since testing provides an objective indication of recent drug use and the overall prevalence of drug use in this drug abusing population has reduced from 100% to < 50%.

  10. Can Artemia Hatching Assay Be a (Sensitive) Alternative Tool to Acute Toxicity Test?

    Science.gov (United States)

    Rotini, A; Manfra, L; Canepa, S; Tornambè, A; Migliore, L

    2015-12-01

    Artemia sp. is extensively used in ecotoxicity testing, despite criticisms inherent to both acute and long-term tests. Alternative endpoints and procedures should be considered to support the use of this biological model. The hatching process comprises several developmental steps and the cyst hatchability seems acceptable as endpoint criterion. In this study, we assessed the reliability of the hatching assay on A. franciscana by comparing with acute and long-term mortality tests, using two chemicals: Diethylene Glycol (DEG), Sodium Dodecyl Sulphate (SDS). Both DEG and SDS tests demonstrated a dose dependent hatching inhibition. The hatching test resulted more sensitive than acute mortality test and less sensitive than the long-term one. Results demonstrate the reliability and high sensitivity of this hatching assay on a short time lag and support its useful application in first-tier risk assessment procedures.

  11. Repeated patch testing to nickel during childhood do not induce nickel sensitization

    DEFF Research Database (Denmark)

    Søgaard Christiansen, Elisabeth

    2014-01-01

    Background: Previously, patch test reactivity to nickel sulphate in a cohort of unselected infants tested repeatedly at 3-72 months of age has been reported. A reproducible positive reaction at 12 and 18 months was selected as a sign of nickel sensitivity, provided a patch test with an empty Finn...... chamber was negative. The objective of this study is to follow-up on infants with suspected nickel sensitivity. Methods: A total of 562 infants were included in the cohort and patch tested with nickel sulphate. The 26 children with a positive patch test to nickel sulphate at 12 and 18 months were offered...... repeated patch test to nickel sulphate at 3 (36 months), 6 (72 months) and 14 years of age. Results: At 3 years, 24 of 26 nickel sensitive children were retested and a positive reaction was seen in 7 children, a negative reaction in 16 and 1 child was excluded due to reaction to both nickel and the empty...

  12. Flow cytometry susceptibility testing for conventional antifungal drugs and Comparison with the NCCLS Broth Macrodilution Test

    Directory of Open Access Journals (Sweden)

    M.J. Najafzadeh

    2009-08-01

    Full Text Available Introduction: During the last decade, the incidence of fungal infection has been increased in many countries. Because of the advent of resistant to antifungal agents, determination of an efficient strategic plan for treatment of fungal disease is an important issue in clinical mycology. Many methods have been introduced and developed for determination of invitro susceptibility tests. During the recent years, flow cytometry has developed to solving the problem and many papers have documented the usefulness of this technique. Materials and methods: As the first step, the invitro susceptibility of standard PTCC (Persian Type of Culture Collection strain and some clinical isolates of Candida consisting of Candida albicans, C. dubliniensis, C. glabrata, C. kefyer and C. parapsilosis were evaluated by macrodilution broth method according to NCCLS (National Committee for Clinical Laboratory Standards guidelines and flow cytometry susceptibility test. Results:  The data indicated that macro dilution broth methods and flow cytometry have the same results in determination of MIC (Minimum Inhibitory Concentration for amphotericin B, clotrimazole, fluconazole, ketoconazole and miconazole in C. albicans PTCC 5027 as well as clinical Candida isolates, such as C.albicans, C.dubliniensis, C.glabrata C.kefyr, and C.parapsilosis. Discussion: Comparing the results obtained by macrodilution broth and flow cytometry methods revealed that flow cytometry was faster. It is suggested that flow cytometry susceptibility test can be used as a powerful tool for determination of MIC and administration of the best antifungal drug in treatment of patients with Candida infections.

  13. The Effectiveness of Mandatory-Random Student Drug Testing. NCEE 2010-4025

    Science.gov (United States)

    James-Burdumy, Susanne; Goesling, Brian; Deke, John; Einspruch, Eric

    2010-01-01

    To help assess the effects of school-based random drug testing programs, the U.S. Department of Education's Institute of Education Sciences (IES) contracted with RMC Research Corporation and Mathematica Policy Research to conduct an experimental evaluation of the Mandatory-Random Student Drug Testing (MRSDT) programs in 36 high schools within…

  14. 49 CFR 40.341 - Must service agents comply with DOT drug and alcohol testing requirements?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Must service agents comply with DOT drug and alcohol testing requirements? 40.341 Section 40.341 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Roles and...

  15. 21 CFR 211.110 - Sampling and testing of in-process materials and drug products.

    Science.gov (United States)

    2010-04-01

    ... PHARMACEUTICALS Production and Process Controls § 211.110 Sampling and testing of in-process materials and drug... production process, e.g., at commencement or completion of significant phases or after storage for long... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sampling and testing of in-process materials...

  16. Second Thoughts on Drug Testing: Balancing Students' Health and Welfare with Their Expectations of Privacy.

    Science.gov (United States)

    Dowling-Sendor, Benjamin

    2000-01-01

    In its "stare decisis" ruling upholding a Pennsylvania school district's random drug-testing policy, a three-judge panel of the Seventh Circuit Court of Appeals nonetheless declared its disagreement with a similar panel's 1998 decision upholding another district's policy of random, suspicionless drug, alcohol, and tobacco testing. (MLH)

  17. 75 FR 22809 - Mandatory Guidelines for Federal Workplace Drug Testing Programs

    Science.gov (United States)

    2010-04-30

    ...: Final rule: Change in effective date. SUMMARY: The Department of Health and Human Services (HHS) is changing the effective date of the Revisions to the Mandatory Guidelines for Federal Workplace Drug Testing... HUMAN SERVICES Mandatory Guidelines for Federal Workplace Drug Testing Programs AGENCY: Substance Abuse...

  18. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    Science.gov (United States)

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the

  19. 49 CFR 219.903 - Retention of drug testing records.

    Science.gov (United States)

    2010-10-01

    .... (4) Records related to employee training: (i) Materials on drug abuse awareness, including a copy of... the following records for a minimum of five years: (i) A summary record of each covered employee's... verifying the existence of a medical explanation of the inability of a covered employee to provide...

  20. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Soolingen, D. van; Mouton, J.W.

    2012-01-01

    Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans. For most NTM infections the therapy of choice is drug treatment, but treatment regimens differ by species, in particular between slow (e.g. Mycobacterium avium complex,

  1. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Soolingen, D. van; Mouton, J.W.

    2012-01-01

    Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans. For most NTM infections the therapy of choice is drug treatment, but treatment regimens differ by species, in particular between slow (e.g. Mycobacterium avium complex, Mycobacter

  2. Rapid detection of in vitro antituberculous drug resistance among smear-positive respiratory samples using microcolony detection-based direct drug susceptibility testing method.

    Science.gov (United States)

    Iftikhar, Irim; Irfan, Seema; Farooqi, Joveria; Azizullah, Zahida; Hasan, Rumina

    2017-01-01

    With the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant Mycobacterium tuberculosis. Although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate microcolony method thin layer agar (TLA) for quick detection of resistance against the first- and second-line antituberculous drugs in clinical isolates. This was a cross-sectional study performed at Aga Khan University Hospital. A total of 87 Z-N stain smear-positive pulmonary samples were received and indirect drug susceptibility test (ID-DST) was performed using Lowenstein-Jensen and mycobacteria growth indicator tube. Direct DST was performed using TLA on 7H10 agar. TLA was observed twice weekly under microscope for 4 weeks. Sensitivity, specificity, and accuracy were calculated for TLA using indirect susceptibility method as the gold standard. Level of agreement was calculated using Kappa score. TLA showed sensitivity of 89% and 95.2% for isoniazid and rifampicin, while for ethionamide, ofloxacin, and injectable aminoglycosides, it was 96.6%, 92.1%, and 100%, respectively. Specificity for the first-line drugs was >95% while second-line drugs ranged from 70% to 100%. Mean time to positivity was 10.2 days by TLA as compared to 43.1 days by ID-DST. TLA is a quick and reliable method in identifying resistance, especially in resource-limited settings. However, additional liquid culture can be set up as backup, especially in patients on therapy to avoid false negative results.

  3. Functional Study of the P32T ITPA Variant Associated with Drug Sensitivity in Humans

    Science.gov (United States)

    Stepchenkova, Elena I.; Tarakhovskaya, Elena R.; Spitler, Kathryn; Frahm, Christin; Menezes, Miriam R.; Simone, Peter D.; Kolar, Carol; Marky, Luis A.; Borgstahl, Gloria E. O.; Pavlov, Youri I.

    2009-01-01

    Sanitization of the cellular nucleotide pools from mutagenic base analogs is necessary for the accuracy of transcription and replication of genetic material and plays a substantial role in cancer prevention. The undesirable mutagenic, recombinogenic and toxic incorporation of purine base analogs (i.e. ITP, dITP, XTP, dXTP or 6-hydroxyaminopurine (HAP) deoxynucleoside triphosphate) into nucleic acids is prevented by inosine triphosphate pyrophosphatase (ITPA). The ITPA gene is a highly conserved, moderately expressed gene. Defects in ITPA orthologs in model organisms cause severe sensitivity to HAP and chromosome fragmentation. A human polymorphic allele 94C->A encodes for the enzyme with a P32T amino acid change and leads to accumulation of non-hydrolyzed ITP. ITPase activity is not detected in erythrocytes of these patients. The P32T polymorphism has also been associated with adverse sensitivity to purine base analog drugs. We have found that the ITPA-P32T mutant is a dimer in solution, as is wild-type ITPA, and has normal ITPA activity in vitro, but the melting point of ITPA-P32T is 5 degrees C lower than that of wild-type. ITPA-P32T is also fully functional in vivo in model organisms as determined by a HAP mutagenesis assay and its complementation of a bacterial ITPA defect. The amount of ITPA protein detected by western blot is severely diminished in a human fibroblast cell line with the 94C->A change. We propose that the P32T mutation exerts its effect in certain human tissues by cumulative effects of destabilization of transcripts, protein stability and availability. PMID:19631656

  4. Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

    Energy Technology Data Exchange (ETDEWEB)

    Jiguet Jiglaire, Carine, E-mail: carine.jiguet-jiglaire@univ-amu.fr [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Metellus, Philippe [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); APHM, Timone Hospital, Department of Neurosurgery, 13005 Marseille (France); Timone Hospital, 264 Rue Saint Pierre, 13385 Marseille Cedex 5 (France); and others

    2014-02-15

    Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening.

  5. Bioluminometric assay of ATP in mouse brain: Determinant factors for enhanced test sensitivity

    Indian Academy of Sciences (India)

    Haseeb Ahmad Khan

    2003-06-01

    Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based on in vitro cell systems. This study reports an optimized FLB procedure for the analysis of ATP in small tissue samples. The results showed that the sensitivity of the FLB test can be enhanced several fold by using ultraturax homogenizer, perchloric acid extraction, neutralization of acid extract and its optimal dilution, before performing the assay reaction.

  6. Meconium drug testing reveals maternal misuse of medicinal opioids among addicted mothers.

    Science.gov (United States)

    Launiainen, Terhi; Nupponen, Irmeli; Halmesmäki, Erja; Ojanperä, Ilkka

    2013-07-01

    Meconium drug testing is a non-invasive method to detect prenatal drug exposure, which can cause severe problems for the infant, indicating the need for follow-up measures to ensure the welfare of the child. Meconium samples for drug testing were collected from 143 infants as part of routine clinical work among addicted mothers. The drug testing findings were combined with medical records including clinical background and follow-up data. The substances screened for included medicinal opioids, 6-monoacetylmorphine (a metabolite of heroin), amphetamines and tetrahydrocannabinolic acid. At least one of the 13 target drugs was detected in 57 (40%) meconium samples. In 21 cases, the findings were unexpected on the basis of clinical data or denied by the mother. Medicinal opioids, especially the opioid substitution treatment drugs buprenorphine and methadone, comprised the majority of the findings of both admitted and unexpected drug misuse. Meconium drug testing methods should target not just traditional illicit drugs but also prescription drugs with misuse potential. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Drug testing welfare recipients--false positives, false negatives, unanticipated opportunities.

    Science.gov (United States)

    Pollack, Harold A; Danziger, Sheldon; Jayakody, Rukmalie; Seefeldt, Kristin S

    2002-01-01

    Substance abuse and dependence are among the most common psychiatric disorders among pregnant and parenting women. These disorders among welfare recipients have attracted special concern. Chemical testing has been proposed to identify illicit drug use in this population. This analysis scrutinizes the potential value of drug testing, using recent data from the Women's Employment Study and the National Household Survey of Drug Abuse. One-fifth of recipients reported illicit substance use during the previous year. However, less than 5% satisfied diagnostic screening criteria for illicit drug dependence. Most recipients with psychiatric disorders or alcohol dependence reported no recent illicit drug use, and, thus, would not be detected through chemical tests. Although illicit drug users are rarely dependent, many face barriers to self-sufficiency. Screening and assessment programs should distinguish use from dependence, and should also identify alcohol dependence and psychiatric disorders. States should provide a range of treatment services to address these concerns.

  8. HIV resistance testing and detected drug resistance in Europe

    NARCIS (Netherlands)

    Schultze, A.; Phillips, A.N.; Paredes, R.; Battegay, M.; Rockstroh, J.K.; Machala, L.; Tomazic, J.; Girard, P.M.; Januskevica, I.; Gronborg-Laut, K.; Lundgren, J.D.; Cozzi-Lepri, A.; Burger, D.M.

    2015-01-01

    OBJECTIVES: To describe regional differences and trends in resistance testing among individuals experiencing virological failure and the prevalence of detected resistance among those individuals who had a genotypic resistance test done following virological failure. DESIGN: Multinational cohort

  9. Maternal sensitivity and language in early childhood: a test of the transactional model.

    Science.gov (United States)

    Leigh, Patricia; Nievar, M Angela; Nathans, Laura

    2011-08-01

    This study examined the relation between mothers' sensitive responsiveness to their children and the children's expressive language skills during early childhood. Reciprocal effects were tested with dyads of mothers and their children participating in the National Institute of Health and Human Development Study of Early Child Care and Youth Development. Sensitive maternal interactions positively affected children's later expressive language in the second and third years of life. Although maternal sensitivity predicted later language skills in children, children's language did not affect later maternal sensitivity as indicated in a structural equation model. These results do not support the 1975 transactional model of child development of Sameroff and Chandler. A consistent pattern of sensitivity throughout infancy and early childhood indicates the importance of fostering maternal sensitivity in infancy for prevention or remediation of expressive language problems in young children.

  10. Swelling characteristics of hydroxyethylmethacrylate/ methacrylic acid pH -sensitive hydrogel as a drug delivery system

    Directory of Open Access Journals (Sweden)

    M. Falamarzian- J. Varshosaz

    1996-08-01

    Full Text Available Hydroxyethyl methacrylate /methacrylic acid (HEMA/MAA copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk.free radical polymerization method. The results indicate that this polymer is a pH -sensitive hydrogel which is collapsed in the acidic medium but completely swollen in the alkaline and neutral pH . it was determined that a proportion of 40% of MAA, the ionizing monomer of this hydrogel, was the best concentration among the different percentages used which showed a non-Fickian water transport mechanism. Increasing MAA content from 20 to 70% was accompanied with a change in water transport mechanism from Fickian to non-Fickian. However, increasing the percentage of MAA from 40 to 70 didn't improve the swelling capacity of this polymer. Pore size determination by a solute exclusion technique, showed the greatest distribution in the hydrogel with 40% MAA compared to other percentages of this monomer used. About 75% of the pores were less than 16.5 A in diameter in this polymer which is important specially in loading the hydrogel with macromoiecular drugs like proteines.

  11. 49 CFR Appendix C to Part 40 - DOT Drug Testing Semi-Annual Laboratory Report to DOT

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false DOT Drug Testing Semi-Annual Laboratory Report to... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. C Appendix C to Part 40—DOT Drug Testing... of Drug and Alcohol Policy and Compliance, W62-300, 1200 New Jersey Avenue, SE., Washington, DC 20590...

  12. 21 CFR 312.160 - Drugs for investigational use in laboratory research animals or in vitro tests.

    Science.gov (United States)

    2010-04-01

    ... research animals or in vitro tests. 312.160 Section 312.160 Food and Drugs FOOD AND DRUG ADMINISTRATION... Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests § 312.160 Drugs for investigational use in laboratory research animals or in vitro tests. (a) Authorization to ship. (1)(i) A...

  13. 46 CFR 4.06-3 - Requirements for alcohol and drug testing following a serious marine incident.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Requirements for alcohol and drug testing following a... drug testing following a serious marine incident. When a marine employer determines that a casualty or... drug testing is conducted: (a) Alcohol testing. (1) Alcohol testing must be conducted on each...

  14. Army Drug Development Program. Phase I. Clinical Testing.

    Science.gov (United States)

    1980-03-01

    ingestion of each formulation. Various symptoms occured - "twitching", "fuzzy spots on ceiling", "feeling hot" and " bad dreams" - which could not be...Counter, Model S. Scientific Product diluents were used for diluting the blood samples ( Isotonic Buffered Saline; Automated Lysing and Hemoglobin Reagent...1), and at 6 a.m. will drink 360 ml of Sustacal (Mead Johnson product), containing a total of 360 calories. The drug will be administered at 8 a.m

  15. Pumpless microfluidic platform for drug testing on human skin equivalents

    OpenAIRE

    Abaci, Hasan Erbil; Gledhill, Karl; Guo, Zongyou; Christiano, Angela M.; Shuler, Michael L.

    2015-01-01

    Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies. In this study, we designed and developed a microfluidic platform that allows for long-term maintenance of full thickness human skin equivalents (HSE) which are comprised of both the epidermal and dermal compartments. The design is based on the physiologically relevant blood residence times in human skin tissue and allows for the establishment of an air-epidermal interface which is crucial for...

  16. Effect of test duration and feeding on relative sensitivity of genetically distinct clades of Hyalella azteca.

    Science.gov (United States)

    Soucek, David J; Dickinson, Amy; Major, Kaley M; McEwen, Abigail R

    2013-11-01

    The amphipod Hyalella azteca is widely used in ecotoxicology laboratories for the assessment of chemical risks to aquatic environments, and it is a cryptic species complex with a number of genetically distinct strains found in wild populations. While it would be valuable to note differences in contaminant sensitivity among different strains collected from various field sites, those findings would be influenced by acclimation of the populations to local conditions. In addition, potential differences in metabolism or lipid storage among different strains may confound assessment of sensitivity in unfed acute toxicity tests. In the present study, our aim was to assess whether there are genetic differences in contaminant sensitivity among three cryptic provisional species of H. azteca. Therefore, we used organisms cultured under the same conditions, assessed their ability to survive for extended periods without food, and conducted fed and unfed acute toxicity tests with two anions (nitrate and chloride) whose toxicities are not expected to be altered by the addition of food. We found that the three genetically distinct clades of H. azteca had substantially different responses to starvation, and the presence/absence of food during acute toxicity tests had a strong role in determining the relative sensitivity of the three clades. In fed tests, where starvation was no longer a potential stressor, significant differences in sensitivity were still observed among the three clades. In light of these differences in sensitivity, we suggest that ecotoxicology laboratories consider using a provisional species in toxicity tests that is a regionally appropriate surrogate.

  17. Status of drugs-of-abuse testing in urine under blind conditions: an AACC study.

    Science.gov (United States)

    Frings, C S; Battaglia, D J; White, R M

    1989-05-01

    We report results of a blind study designed to determine the accuracy of drugs-of-abuse testing in urine as done in 31 laboratories across the United States. The drugs studied were amphetamines, cannabinoids, cocaine, opiates, and phencyclidine. These laboratories confirmed all positive drug results with a different analytical method. Ten urine samples were sent to each laboratory, which resulted in 1486 trials. There were no false-positive results. The overall accuracy rate was 97%. Our study demonstrates that urine drug testing can be accurate when performed by qualified staff, using up-to-date screening and confirmation methods, appropriate quality-assurance measures, and a chain of custody.

  18. Development, implementation and management of a drug testing program in the workplace

    Energy Technology Data Exchange (ETDEWEB)

    Burtis, C.A.

    1990-01-01

    To combat the rising use of drugs in the workplace many American companies have implemented drug testing programs and are testing employees and job applicants for use of illegal drugs. In addition, on September 15, 1986, Executive Order No.12564 was issued by President Reagan, which requires all federal agencies to develop programs and policies, one of the goals of which is to achieve a drug-free federal workplace. Included in this Executive Order is the requirement that federal agencies implement drug testing has become a prevalent practice as a means to detect and deter drug use in the workplace. Before a drug testing program is implemented, it is imperative that policies and procedures are developed that (1) ensure the accuracy of test results, (2) protect the validity and integrity of the specimen, (3) guarantee due process, and (4) maintain confidentiality. To make certain that these prerequisites were met in the government drug testing programs, the US Department of Health and Human Services (HHS) was directed to develop technical and scientific guidelines for conducting such programs. 15 refs., 1 fig., 2 tabs.

  19. Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

    Directory of Open Access Journals (Sweden)<