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1

Ebola Drug Shows Promise in Monkey Trial  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Ebola Drug Shows Promise in Monkey Trial Experimental medicine ... Mozes Tuesday, February 10, 2015 Related MedlinePlus Page Ebola TUESDAY, Feb. 10, 2015 (HealthDay News) -- An investigational ...

2

New Drug Shows Promise for MS  

MedlinePLUS

... 2015) Tuesday, April 14, 2015 Related MedlinePlus Page Multiple Sclerosis TUESDAY, April 14, 2015 (HealthDay News) -- An experimental drug appears to repair nerve damage seen in multiple sclerosis (MS) patients, results of an early trial suggest. ...

3

Family Checkup: Positive Parenting Prevents Drug Abuse  

MedlinePLUS

... Home » Family Checkup Family Checkup: Positive Parenting Prevents Drug Abuse Email Facebook Twitter Revised October 2012 Could your ... drugs. Research supported by the National Institute on Drug Abuse (NIDA) has shown the important role that parents ...

4

New Drug for Crohn's Disease Shows Early Promise  

MedlinePLUS

... sharing features on this page, please enable JavaScript. New Drug for Crohn's Disease Shows Early Promise But ... not involved in the study. In theory, the new drug -- dubbed mongersen -- could be safer than existing ...

5

[Incretin mimetic drugs: therapeutic positioning].  

PubMed

Type 2 diabetes is a chronic and complex disease, due to the differences among affected individuals, which affect choice of treatment. The number of drug families has increased in the last few years, and these families have widely differing mechanisms of action, which contributes greatly to the individualization of treatment according to the patient's characteristics and comorbidities. The present article discusses incretin mimetic drugs. Their development has been based on knowledge of the effects of natural incretin hormones: GLP-1 (glucagon-like peptide 1), GIP (glucose-dependent insulinotropic peptide) and dipeptidyl peptidase enzyme 4 (DPP4), which rapidly degrade them in the systemic circulation. This group is composed of 2 different types of molecules: GLP-1 analogs and DPP4 enzyme inhibitors. The benefits of these molecules include a reduction in plasma glucose without the risk of hypoglycemias or weight gain. There are a series of questions that require new studies to establish a possible association between the use of these drugs and notification of cases of pancreatitis, as well as their relationship with pancreatic and thyroid cancer. Also awaited is the publication of several studies that will provide information on the relationship between these drugs and cardiovascular risk in people with diabetes. All these questions will probably be progressively elucidated with greater experience in the use of these drugs. PMID:25311717

López Simarro, F

2014-07-01

6

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

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

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

7

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

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

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

8

Experimental Drug Shows Promise in Lowering Cholesterol, Heart Attack Risk  

MedlinePLUS

... enable JavaScript. Experimental Drug Shows Promise in Lowering Cholesterol, Heart Attack Risk Adding the 'investigational biologic' evolocumab ... 2015) Monday, March 16, 2015 Related MedlinePlus Pages Cholesterol Heart Attack Medicines SUNDAY, March 15, 2015 (HealthDay ...

9

Screening Test Finds Drugs That Show Promise Against Ebola  

MedlinePLUS

... Screening Test Finds Drugs That Show Promise Against Ebola Researchers uncover 53 potential treatments; all are already ... 2015) Wednesday, December 17, 2014 Related MedlinePlus Pages Ebola Medicines WEDNESDAY, Dec. 17, 2014 (HealthDay News) -- A ...

10

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

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

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

11

7. VIEW LOOKING NORTHWEST SHOWING MOVABLE SPAN IN OPEN POSITION ...  

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

7. VIEW LOOKING NORTHWEST SHOWING MOVABLE SPAN IN OPEN POSITION - New York, New Haven & Hartford Railroad, Groton Bridge, Spanning Thames River between New London & Groton, New London, New London County, CT

12

6. VIEW LOOKING NORTHWEST SHOWING MOVABLE SPAN IN CLOSED POSITION ...  

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

6. VIEW LOOKING NORTHWEST SHOWING MOVABLE SPAN IN CLOSED POSITION - New York, New Haven & Hartford Railroad, Groton Bridge, Spanning Thames River between New London & Groton, New London, New London County, CT

13

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

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

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

14

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

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

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

15

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

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

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

16

[Positive interaction between immunosuppressive and antifungal drugs].  

PubMed

Immunosuppressive and antifungal drugs are frequently associated to treat solid organ transplant patients or patients with hematological malignancies. To cure invasive fungal infection (IFI), immunosuppression has to be reduced. However, immunosuppressive drugs such as cyclosporin A, tacrolimus, sirolimus (rapamycin) or mycophenolate mofetil possess antifungal properties. Indeed fungi and humans have in common calcineurin and TOR signalization pathways which are inhibited by these molecules. In vitro experiences suggest a positive interaction between immunosuppressive and antifungal drugs such as amphotericin B, azole and echinocandins. These results are confirmed by clinical findings and thus offer further therapeutic possibilities in the context of solid organ transplantation. double dagger. PMID:20819713

Rammaert, Blandine; Lortholary, Olivier

2010-01-01

17

[How children show positive and negative relationships on their drawings].  

PubMed

This study analyses, whether pictures of children showing a positive relationship are significantly different from those showing a negative one with respect to several criteria. The study involved a random selection of 45 children aged 4;6 to 11;6 years. The children painted a picture with themselves and a person they liked and a picture of themselves with someone they disliked. For the most part, the children drew pictures of themselves with peers both with respect to positive as well as negative images. In an interview afterwards, the children specified the criteria in their drawings by which the quality of the particular relationship can be identified. Positive and negative relationship paintings differ in the character of activity described. The sun as an element in children's paintings is painted not more frequent on positive compared to negative pictures. The colour black is used more often in the drawings signifying negative relationships. While girls used more colour in negative relationship drawings, boys used more colour in the positive ones. There was no significant difference in the use of favourite colours and decorative elements between the two groups. Only in negative relationship drawings people were looking away from each other. Smiling individuals were more common in the positive relationship pictures and in pictures painted by the 6 to 8 year olds. A greater distance between the individuals emerged on negative relationship drawings of the girls. PMID:15730148

Gramel, Sabine

2005-01-01

18

Emerging Trends in Contextual Learning Show Positive Results for Students.  

ERIC Educational Resources Information Center

This issue focuses on contextual learning (CL), in which students master rigorous academic content in real-world or work-based learning experiences. "Emerging Trends in CL Show Positive Results for Students" discusses CL as an important strategy for improving student achievement. It describes: how CL raises the bar for all students, challenging…

WorkAmerica, 2001

2001-01-01

19

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

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

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

20

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

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

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

21

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

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

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

22

MEK: A Single Drug Target Shows Promise in Multiple Cancers  

Cancer.gov

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

23

Multisite study shows drug offers relief for symptoms of myelofibrosis  

Cancer.gov

People with a blood cancer — myelofibrosis — can benefit from a drug called ruxolitinib, according to a randomized, double-blind, placebo-controlled clinical trial that included patients and researchers from the Stanford University School of Medicine, MD Anderson Cancer Center, and the Mayo Clinic in Scottsdale, Ariz.

24

Use of Preventative and Therapeutic Drugs in Show Market Animals  

E-print Network

label, package, package insert or feed tag. The with- drawal time is the length of time required for the substance to be eliminated from the animal?s body or to be reduced to a safe (tolerance) level prior to slaughter. The drug, chemical or feed... additive is to be withdrawn for the number of days listed on the label before the animal is slaughtered. If there is no withdrawal time on a product label, it means the substance either is safe or is reduced to a safe level in the animal within 24 hours...

Faries Jr., Floron C.

2001-03-12

25

New cancer drug shows promise for treating advanced melanoma  

Cancer.gov

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

26

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

PubMed Central

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

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

2012-01-01

27

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

Cancer.gov

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

28

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

ERIC Educational Resources Information Center

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

Vedder, Charles B.

29

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

MedlinePLUS

... 2003 2002 2001 2000 1999 Spotlight on Research 2013 August 2013 Novel Drug Delivery System Shows Early Promise for ... systemic lupus erythematosus in mice. J Clin Invest. 2013;123(4):1741-1749. PMID: 23454752. The mission ...

30

Crizotinib Continues to Show Promise for Some Lung Tumors, Faces Challenge of Drug Resistance  

Cancer.gov

New data from a phase I trial of crizotinib, a small-molecule drug that targets cancer-causing chromosomal rearrangements involving the gene ALK, in patients with non-small cell lung cancer add to positive results published October 28, 2010, in the New England Journal of Medicine.

31

International phase I clinical trial shows drug shrinks melanoma brain metastases  

Cancer.gov

An experimental drug targeting a common mutation in melanoma successfully shrank tumors that spread to the brain in nine out of 10 patients in part of an international phase I clinical trial report in the May 18 issue of The Lancet. The drug dabrafenib, which targets the Val600 BRAF mutation that is active in half of melanoma cases, also cut the size of tumors in 25 of 36 patients with late-stage melanoma that had not spread to the brain. The drug also showed activity in other cancer types with the BRAF mutation.

32

A Multifunctional Drug Combination Shows Highly Potent Therapeutic Efficacy against Human Cancer Xenografts in Athymic Mice  

PubMed Central

The tumor microenvironment plays a crucial role during tumor development. Integrated combination of drugs that target tumor microenvironment is a promising approach to anticancer therapy. Here, we report a multifunctional combination of low-cytotoxic drugs composed of dipyridamole, bestatin and dexamethasone (DBDx) which mainly acts on the tumor microenvironment shows highly potent antitumor efficacy in vivo. In mouse hepatoma H22 model, the triple drug combination showed synergistic and highly potent antitumor efficacy. The combination indices of various combinations of the triple drugs were between 0.2 and 0.5. DBDx inhibited the growth of a panel of human tumor xenografts and showed no obvious systemic toxicity. At tolerated doses, DBDx suppressed the growth of human hepatocellular carcinoma BEL-7402, HepG2, and lung adenocarcinoma A549 xenografts by 94.5%, 93.7% and 96.9%, respectively. Clonogenic assay demonstrated that DBDx showed weak cytotoxicity. Western blot showed that Flk1 and Nos3 were down-regulated in the DBDx-treated group. Proteomic analysis showed that DBDx mainly affected the metabolic process and immune system process; in addition, the angiogenesis and VEGF signaling pathway were also affected. Conclusively, DBDx, a multifunctional drug combination of three low-cytotoxic drugs, shows synergistic and highly potent antitumor efficacy evidently mediated by the modulation of tumor microenvironment. Based on its low-cytotoxic attributes and its broad-spectrum antitumor therapeutic efficacy, this multifunctional combination might be useful in the treatment of cancers, especially those refractory to conventional chemotherapeutics. PMID:25531414

Li, Yi; Wu, Shu-Ying; Zhen, Yong-Su

2014-01-01

33

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

PubMed

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

Gopal, Pooja; Dick, Thomas

2015-04-01

34

Temple researchers show targeted cancer drug may stunt heart's ability to repair itself  

Cancer.gov

Scientists for the first time have evidence showing how a widely used type of "targeted" cancer drug can be dangerous to the heart. Studying mice with the equivalent of a heart attack, Temple University School of Medicine researchers found that the drug sorafenib (Nexavar) – which inhibits proteins called tyrosine kinase receptors (RTKs), and is used in kidney and liver cancer treatment – can interfere with heart stem cell activity, affecting the heart's ability to repair itself after injury. The findings suggest that sorafenib and other similar drugs that target these kinds of protein receptors may raise the risk for heart attack for some cancer patients with underlying heart disease, as well as affect the heart's ability to repair damage. Temple is home to the Fox Chase Cancer Center.

35

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

PubMed Central

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

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

2008-01-01

36

The Fluency Amplification Model: fluent stimuli show more intense but not evidently more positive evaluations.  

PubMed

Processing fluency plays a large role in forming judgments, as research repeatedly shows. According to the Hedonic Fluency Model, more fluently processed stimuli are rated more affectively positive than less fluently processed stimuli. Most research documenting such findings uses neutral or positive stimuli with low complexity, thus any potential impact of initial stimulus valence cannot be tested. In the present study, 60 IAPS stimuli ranging from very negative to very positive valence were rated on liking by participants. Processing fluency was manipulated through perceptual priming (7 ms). Results of Experiment 1 (N = 35) support the prediction of the Hedonic Fluency Model, but only for stimuli with an initially positive valence. However, when negative stimuli were processed more fluently, they were rated as more negative than when processed less fluently. Experiment 2 (N = 39) showed that enhancing the accessibility of the stimulus content (via prolonging the prime duration to 100 ms) cannot account for the results of Experiment 1, since Experiment 2 failed to replicate the findings obtained in Experiment 1. Potential factors influencing affective evaluation of negative stimuli are discussed. A model is offered for the reinterpretation of processing fluency as an amplifying factor for evaluative judgment. PMID:24603044

Albrecht, Sabine; Carbon, Claus-Christian

2014-05-01

37

Upper airway collapse during drug induced sleep endoscopy: head rotation in supine position compared with lateral head and trunk position.  

PubMed

Drug induced sedated sleep endoscopy (DISE) is often employed to determine the site, severity and pattern of obstruction in patients with sleep apnea. DISE is usually performed in supine position. We recently showed that the obstruction pattern is different when DISE is performed in lateral position. In this study, we compared the outcomes of DISE performed in supine position with head rotated, with the outcomes of DISE performed with head and trunk in lateral position. The Prospective study design was used in the present study. Sixty patients with OSA (44 male; mean apnea hypopnea index (AHI) 20.8 ± 17.5 events/h) underwent DISE under propofol sedation. Patients were placed in lateral position, and the upper airway collapse was evaluated. The patients were then placed in supine position with the head rotated to the right side. DISE outcomes were scored using the VOTE classification system. In lateral position, nine patients (15.0%) had a complete antero-posterior (A-P) collapse at the level of the velum, nine had a partial A-P collapse. During head rotation and trunk in supine position, at the level of the velum, four patients (6.7%) had a complete A-P collapse, while two patients (3.3%) had a partial A-P collapse. For all other sites, the patterns of collapse were not significantly different between head rotation and lateral position. During DISE, rotation of the head in supine position, and lateral head and trunk position present similar sites, severity and patterns of upper airway collapse, with the exception of collapse at the level of the velum. Here the severity of A-P collapse is less severe during head rotation than in lateral head and trunk position. PMID:25142078

Safiruddin, Faiza; Koutsourelakis, Ioannis; de Vries, Nico

2015-02-01

38

Legal Position of School Personnel -- Drugs and Narcotics.  

ERIC Educational Resources Information Center

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

Shannon, Thomas A.

39

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

PubMed

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

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

2014-07-01

40

Sca1-positive murine pituitary adenoma cells show tumor growth advantage  

PubMed Central

The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. We investigated whether cells within pituitary adenomas that spontaneously develop in Rb+/? mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with EGF and bFGF. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1+ cell population that showed increased sphere formation potential, lower hormone mRNA expression, higher expression of stem cell markers (Notch1, Sox2, Nestin), and increased proliferation rates. When transplanted into NOD scid gamma mice brains, Sca1+ pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 [100%] vs. 7/12 [54%] of mice transplanted with Sca1+ and Sca1? cells, respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that those derived from Sca1+ pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1+ cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells. PMID:24481638

Donangelo, Ines; Ren, Song-Guang; Eigler, Tamar; Svendsen, Clive; Melmed, Shlomo

2014-01-01

41

Drug abusers show impaired performance in a laboratory test of decision making  

Microsoft Academic Search

A defining feature of drug addiction is persistent drug use despite long-term adverse consequences. This study examined the performance of drug abusers on a neuropsychological test that requires evaluation of long-term outcomes in the presence of a complex set of mixed reward\\/punishment contingencies (the Gambling Task). In order to control for generalized deficits related to choice and planning, subjects were

Steven Grant; Carlo Contoreggi; Edythe D. London

2000-01-01

42

Dana-Farber study shows that three 'targeted' cancer drugs raise risk of fatal side effects  

Cancer.gov

Treatment with three relatively new "targeted" cancer drugs has been linked to a slightly elevated chance of fatal side effects, according to a new analysis led by scientists at Dana-Farber Cancer Institute.

43

University of Maryland study shows commonly used diabetes drug may help prevent primary liver cancer  

Cancer.gov

Metformin, a drug widely used to treat Type II diabetes, may help to prevent primary liver cancer, researchers at the University of Maryland Marlene and Stewart Greenebaum Cancer Center report in the April 1, 2012, issue of Cancer Prevention Research.

44

Mayo Clinic study finds combination of Avastin, second drug shows promise fighting brain cancer  

Cancer.gov

The drug bevacizumab, also known by the trade name Avastin, shrinks tumors briefly in patients with an aggressive brain cancer known as glioblastoma multiforme, but then they often grow again and spread throughout the brain for reasons no one previously has understood. Now, Mayo Clinic researchers have found out why this happens. They have also discovered that, in animals, pairing Avastin with another cancer drug, dasatinib, can stop that lethal spread. Dasatinib is approved for use in several blood cancers.

45

Research & market strategy: how choice of drug discovery approach can affect market position.  

PubMed

In principal, drug discovery approaches can be grouped into target- and function-based, with the respective aims of developing either a target-selective drug or a drug that produces a specific biological effect irrespective of its mode of action. Most analyses of drug discovery approaches focus on productivity, whereas the strategic implications of the choice of drug discovery approach on market position and ability to maintain market exclusivity are rarely considered. However, a comparison of approaches from the perspective of market position indicates that the functional approach is superior for the development of novel, innovative treatments. PMID:17395091

Sams-Dodd, Frank

2007-04-01

46

Predicting Positive Attitudes About Quitting Drug and Alcohol Use Among Homeless Women  

Microsoft Academic Search

Two separate path models for alcohol and drugs were tested in which psychosocial, environmental, and sociodemographic variables predicted behavioral and substance abuse related factors as well as the key outcome of positive attitudes about quitting drugs (N = 620) or alcohol (N = 526) in a sample of 709 homeless women. A positive attitude about quitting alcohol was predicted by

Adeline M. Nyamathi; Judith A. Stein; Elizabeth Dixon; Douglas Longshore; Elisha Galaif

2003-01-01

47

A case of fatal drug intoxication showing a high-density duodenal content by postmortem computed tomography.  

PubMed

A 22-year-old woman was found dead in her bed, and subsequent postmortem examination was performed using ordinary methods such as external examination, Triage®, and computed tomography (CT) scan which demonstrated a high-density content of the duodenum. Autopsy and quantitative analysis of drugs present in the GI tract showed that high amounts of radiopaque psychotic agents such as fluvoxamine maleate, carbamazepine, and zolpidem tartrate had been responsible for the high-density profile of the duodenum. Postmortem quantitative analysis of drugs in the blood suggested that death had been caused by fatal intoxication with fluvoxamine maleate. Thus, postmortem CT could offer an opportunity to suspect drug intoxication due to radiopaque psychotic agents such as chloral hydrate, phenothiazine, bromovaleryl urea, fluvoxamine maleate, and probably zolpidem tartrate, although it is neither a specific nor a quantitative test for drugs. Therefore, postmortem CT happened to provide clues to investigation of drug intoxication in the present case. PMID:21134778

Sano, Rie; Takahashi, Keiko; Kominato, Yoshihiko; Araki, Takuya; Yamamoto, Koujiro; Takei, Hiroyuki; Otake, Hidenori; Awata, Sachiko; Akuzawa, Hisashi; Tago, Yoko; Aoki, Hideo

2011-01-01

48

Additional drug shows promise for women with triple-negative breast cancer  

Cancer.gov

In a nationwide study of women with triple-negative breast cancer, adding the chemotherapy drug carboplatin or the angiogenesis inhibitor Avastin to standard chemotherapy drugs brought a sharp increase in the number of patients whose tumors shrank away completely, investigators reported at the 2013 San Antonio Breast Cancer Symposium. The study, sponsored by the Cancer and Leukemia Group B, includes authors from the Dana-Farber Cancer Institute, Brown University, the University of Texas MD Anderson Cancer Center, the UNC Lineberger Comprehensive Cancer Center. New York University, Washington University in St. Louis, City of Hope Comprehensive Cancer Center, and Mount Sinai Medical Center.

49

In Sloan-Kettering study, new drug shows promise for patients with advanced kidney cancer  

Cancer.gov

People with advanced kidney cancer may have a new alternative in their limited arsenal of treatment options that are both well tolerated and effective against the disease. New research led by Memorial Sloan-Kettering has shown that the investigational drug tivozanib is more effective than an approved targeted therapy called sorafenib (Nexavar®) in delaying the growth of their cancer.

50

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

Cancer.gov

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

51

Rethinking drug policy: an integrity preserving compromise position  

E-print Network

claim the drug is not deadly or carcinogenic and can be helpful as an analgesic, in treating anxiety, nausea, glaucoma, migraines, anorexia, and a myriad of other conditions.xvii If true, this undermines DEA?s insistence that marijuana is potentially...

Crispino, Azzurra

2006-10-30

52

Drug used in NIH-supported trial shows benefit in children with previously treated cancers  

Cancer.gov

Young patients with some types of advanced cancer, for whom standard treatment had failed, had their tumors disappear during treatment with a drug that both targets and blocks a protein associated with their disease. These findings are from a Phase I, multicenter trial, led by investigators from the Children's Oncology Group (COG), and supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

53

Studies show new drug to be effective in treating skin cancer  

Cancer.gov

A clinical study has demonstrated that a new drug, a targeted molecular therapy called vismodegib (trade name Erivedge), can dramatically shrink basal cell skin cancers and prevent the formation of new ones, in patients with basal cell nevus syndrome (BCNS). This rare genetic condition causes dozens, and sometimes hundreds or thousands, of skin cancers on each patient’s body. The primary treatment option is surgical removal. These study results are significant as they indicate the possibility of an alternative treatment with oral medication; although side effects remain a consideration.

54

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

PubMed

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

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

2014-09-01

55

Drug poisoning deaths in Sweden show a predominance of ethanol in mono-intoxications, adverse drug-alcohol interactions and poly-drug use.  

PubMed

Over a 10-year period (1998-2007) all deaths in Sweden classified by forensic pathologists as fatal drug poisonings (N = 6894) were retrieved from a toxicology database (TOXBASE) belonging to the National Board of Forensic Medicine. The deaths were further classified as suicides N = 2288 (33%), undetermined N = 2260 (33%) and accidental N = 2346 (34%). The average age (± SD) of all victims was 49.1 ± 15.9 years and men 47.4 ± 15.6 years were 5-year younger than women 52.2 ± 15.8 years (p < 0.01). Most of the deceased (78%) were poly-drug users although a single drug (mono-intoxications) was found in 22% of all poisoning deaths (p < 0.001). The number of drugs in blood samples varied from 1 to 12 with a median of 3-4 per case. Mono-intoxication deaths were mostly ethanol-related (N = 976) and the mean and median blood-alcohol concentration (BAC) was 3.06 g/L and 3.10 g/L, respectively. The BAC decreased as the number of additional drugs in blood increased from 2.15 g/L with one drug to 1.25 g/L with 6 or more drugs. The mean (median) concentrations of non-alcohol drugs in mono-intoxication deaths were morphine (N = 93) 0.5mg/L (0.2mg/L), amphetamine (N = 39) 2.0mg/L (1.2mg/L), dextropropoxyphene (N = 33) 3.9 mg/L (2.9 mg/L), dihydro-propiomazine (N = 32) 1.6 mg/L (1.0mg/L) and 7-amino-flunitrazepam (N = 28), 0.4 mg/L (0.3mg/L). Elevated blood morphine in these poisoning deaths mostly reflected abuse of heroin as verified by finding 6-monoacetyl morphine (6-MAM) in the blood samples. When investigating drug poisoning deaths a comprehensive toxicological analysis is essential although the results do not reveal the extent of prior exposure to drugs or the development of pharmacological tolerance. The concentrations of drugs determined in post-mortem blood are one element in the case. The autopsy report, the police investigation, the findings at the scene and eye-witness statements should all be carefully considered when the cause and manner of death are determined. PMID:20630671

Jones, A W; Kugelberg, F C; Holmgren, A; Ahlner, J

2011-03-20

56

Do rewardless orchids show a positive relationship between phenotypic diversity and reproductive success?  

PubMed

Among rewardless orchids, pollinator sampling behavior has been suggested to drive a positive relationship between population phenotypic variability and absolute reproductive success, and hence population fitness. We tested this hypothesis by constructing experimental arrays using the rewardless orchid Dactylorhiza sambucina, which is dimorphic for corolla color. We found no evidence that polymorphic arrays had higher mean reproductive success than monomorphic arrays for pollinia removal, pollen deposition, or fruit set. For pollinia removal, monomorphic yellow arrays had significantly greater reproductive success, and monomorphic red the least. A tendency for yellow arrays to have higher pollen deposition was also found. We argue that differential population fitness was most likely to reflect differential numbers of pollinators attracted to arrays, through preferential long-distance attraction to arrays with yellow inflorescences. Correlative studies of absolute reproductive success in 52 populations of D. sambucina supported our experimental results. To our knowledge this is the first study to suggest that attraction of a greater number of pollinators to rewardless orchids may be of greater functional importance to population fitness, and thus ecology and conservation, than are the behavioral sequences of individual pollinators. PMID:17479761

Smithson, Ann; Juillet, Nicolas; Macnair, Mark R; Gigord, Luc D B

2007-02-01

57

Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects  

PubMed Central

AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms. PMID:25593485

Johannesson, Elisabet; Ringström, Gisela; Abrahamsson, Hasse; Sadik, Riadh

2015-01-01

58

Visceral and post-Kala-Azar dermal leishmaniasis isolates show significant difference in their in vitro drug susceptibility pattern.  

PubMed

Visceral leishmaniasis (VL) remains a major health problem in old world, and India accounts for half of the world burden. The widespread emergence of resistance to standard drug in India poses a major obstacle in the control of leishmaniasis. Post-Kala-Azar dermal leishmaniasis (PKDL) is considered as main source of drug resistance. Experimental data indicate that resistance against newer drugs is also imminent. Therefore, in vitro studies were carried out to test minimum parasiticidal concentration of five conventional and newly introduced anti-leishmanial drugs against 20 field isolates of Leishmania donovani obtained from visceral and post-Kala-Azar dermal leishmaniasis patients of India. Study revealed wide range of variation in minimum inhibitory concentration of sodium antimony gluconate (SAG). PKDL isolates displayed significantly lower susceptibility to SAG and miltefosine than VL isolates with P value of 0.0006 and 0.0243, respectively. All clinical isolates had higher IC(50) value for paromomycin and miltefosine as compared to reference strain indicating their vulnerability to develop unresponsiveness. However, isolates were uniformly susceptible to pentamidine and amphotericin B. The results of gene expression analysis of AQP1 were largely in agreement with phenotypic drug sensitivity results. Interestingly, significant down-regulation of AQP1 was observed in PKDL isolates as compared to VL isolates indicating their increased propensity for drug unresponsiveness. However, no significant difference in mRNA expression of LdMT and LdRos3 gene was found for two groups. The present study unravels valuable baseline scientific data showing variation in the drug susceptibility pattern in the L. donovani isolates. The information might have impact on the management and control of Indian visceral leishmaniasis. PMID:23242321

Mishra, Jyotsna; Madhubala, Rentala; Singh, Sarman

2013-03-01

59

Azvudine, A Novel Nucleoside Reverse Transcriptase Inhibitor Showed Good Drug Combination Features and Better Inhibition on Drug-Resistant Strains than Lamivudine In Vitro  

PubMed Central

Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC50s ranging from 0.03 to 6.92 nM) and HIV-2 (EC50s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range. PMID:25144636

Wang, Rui-Rui; Yang, Qing-Hua; Luo, Rong-Hua; Peng, You-Mei; Dai, Shao-Xing; Zhang, Xing-Jie; Chen, Huan; Cui, Xue-Qing; Liu, Ya-Juan; Huang, Jing-Fei; Chang, Jun-Biao; Zheng, Yong-Tang

2014-01-01

60

Drug shows potential as safe and effective for chronic leukemia, mantle cell lymphoma  

Cancer.gov

Two clinical studies published in the New England Journal of Medicine with an accompanying editorial suggest that the novel agent ibrutinib shows real potential as a safe, effective, targeted treatment for adults with chronic lymphocytic leukemia (CLL) and for patients with mantle cell lymphoma (MCL). Both studies, co-led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and at MD Anderson Cancer Center, were published in the Journal’s June 19, 2013 online edition.

61

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

PubMed Central

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

Hölscher, Christian

2014-01-01

62

Cyp1a2(-/-) null mutant mice develop normally but show deficient drug metabolism.  

PubMed Central

Cytochrome P450 1A2 (CYP1A2) is a predominantly hepatic enzyme known to be important in the metabolism of numerous foreign chemicals of pharmacologic, toxicologic, and carcinogenic significance. CYP1A2 substrates include aflatoxin B1, acetaminophen, and a variety of environmental arylamines. To define better the developmental and metabolic functions of this enzyme, we developed a CYP1A2-deficient mouse line by homologous recombination in embryonic stem cells. Mice homozygous for the targeted Cyp1a2 gene, designated Cyp1a2(-/-), are completely viable and fertile; histologic examination of 15-day embryos, newborn pups, and 3-week-old mice revealed no abnormalities. No CYP1A2 mRNA was detected by Northern blot analysis. Moreover, mRNA levels of Cyp1a1, the other gene in the same subfamily, appear unaffected by loss of the Cyp1a2 gene. Because the muscle relaxant zoxazolamine is a known substrate for CYP1A2, we studied the Cyp1a2(-/-) genotype by using the zoxazolamine paralysis test: the Cyp1a2(-/-) mice exhibited dramatically lengthened paralysis times relative to the Cyp1a2(+/+) wild-type animals, and the Cyp1a2(+/-) heterozygotes showed an intermediate effect. Availability of a viable and fertile CYP1A2-deficient mouse line will provide a valuable tool for researchers wishing to define the precise role of CYP1A2 in numerous metabolic and pharmacokinetic processes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8643688

Liang, H C; Li, H; McKinnon, R A; Duffy, J J; Potter, S S; Puga, A; Nebert, D W

1996-01-01

63

Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey  

PubMed Central

Introduction The objective of this study was to determine the transmitted drug resistance mutations (TDRMs) in newly diagnosed HIV-1 positive patients in Turkey. Materials and Methods The study was carried out between 2009 and 2014 and antiretroviral naïve 774 HIV-1 infected patients from 19 Infectious Diseases and Clinical Microbiology Departments in Turkey were included; gender: 664 (86%) male, median age: 37 (range; 1–77), median CD4+T-cell: 360 (range; 1–1320) count/mm3, median HIV-RNA load: 2.10+E6 (range; 4.2+E2–7.41+E8) IU/mL. HIV-1 drug resistance mutations were detected by population based sequencing of the reverse transcriptase (codon 41–238) and protease (codon 1–99) domains of pol gene of HIV-1, and analyzed according to the criteria by the World Health Organization 2009 list of surveillance drug resistance mutations [1]. Results The patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). The prevalence of overall TDRMs was 6.7% (52/774). Resistance mutations were found to be 0.7% (6/774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug groups, respectively. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N) as multi-class drug resistance. However, thymidine analogue resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV-1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774) and 4.3% (34/774), respectively. Conclusions The TDRMs prevalence of antiretroviral naïve HIV-1 infected patients may be suggested current situation of Turkey. These long-term and large-scale results show that the resistance testing must be an integral part of the management of HIV infection in Turkey. PMID:25397495

Sayan, Murat; Sargýn, Fatma; Inan, Dilara; Yýldýz Sevgi, Dilek; Kocagül Celikbas, Aysel; Yasar, Kadriye; Kaptan, Figen; Sayýn Kutlu, Selda; Tasdelen Fýsgýn, Nuriye; Inci, Ayse; Ceran, Nurgül; Karaoðlan, Ýlkay; Cagatay, Atahan; Kemal Celen, Mustafa; Tekin Koruk, Suda; Ceylan, Bahadýr; Yýldýrmak, Taner; Akalýn, Halis; Korten, Volkan; Willke, Ayse

2014-01-01

64

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

PubMed

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

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

2009-07-01

65

[The experience of nurses caring for HIV-positive injection drug users].  

PubMed

Taiwan has experienced a clear upswing in HIV infection among injection drug users (IDUs) since 2004. Unsafe drug injection behavior has led to complicated infections including HIV and hepatitis C virus infection among IDUs. Nurses face challenges and threats in caring for this group due to the widespread criminal and behavioral problems related to drug use. The purpose of this phenomenological study was to explore nurses' experiences in caring for HIV positive IDUs. Purposive sampling was used to recruit 7 nurses with experience working with HIV positive IDUs. In-depth semi-structured interviews were conducted 1~2 times with each nurse. The length of interviews ranged from 1.5~3 hours. Interviews were tape recorded and transcribed verbatim. Data was analyzed using the Colaizzi method for phenomenology. Nurse experiences reflected low achievement level, difficulty in establishing rapport with IDUs, fear of drug use incidences during hospitalization, insufficiency and complications with family caregivers, fear of being threatened, and lack of support from other medical disciplines. Nurses used strategies that included being supportive of one another, learning appropriate communication skills, positive thinking, and anticipating substantial compensation from administrators. The results of this study provide essential information for in-service education and healthcare policy reform on IDU care. Interventions to ease nurse anxieties and feelings of insecurity in order to increase safe care should be developed and implemented. Positive feedback from IDUs with HIV infection enhances nurses' professional and personal growth. PMID:19634096

Feng, Ming-Chu; Chen, Tun-Chieh; Lin, Chiu-Chu; Shih, Chung-Ching; Ko, Nai-Ying

2009-08-01

66

Comparative study on toxoplasma serology among HIV positive and HIV negative illicit drug users in Ahvaz, Iran  

PubMed Central

Background: Toxoplasmosis is a common parasitic infection in human around the world and can cause life-threatening encephalitis in human immunodeficiency virus (HIV) infected host. The aim of this study was to assess the frequency of toxoplasma infection in illicit drug users (IDUs) with and without HIV infection in Iran. Methods: This study was carried out on 84 IDUs (42 HIV positive as case group and 42 HIV negative subjects as control group) from 2008 to 2009. Serum samples were tested for T. gondii IgG antibodies by Enzym linked immunosorbant assay (ELISA). Based on the company brochure kit, the test was defined positive if the antibody titer was 3 IU/ml or more. The data from these two groups were collected and analyzed. Results: The mean age of HIV positive cases was 34.4±8.6 and for HIV negative cases was 35.9±9.3 year. The mean age and distribution of sex in both groups were equal. The frequency of toxoplasma-IgG in HIV positive and HIV negative was 73.8% and 81%, respectively (p=0.19). Conclusion: The results show that prevalence of toxoplasmosis infection in the illicit drug users with HIV positive or negative is equal. PMID:24294474

Alavi, Seyed Mohammad; Jamshidian, Ramin; Salmanzadeh, Shokrolah

2013-01-01

67

Trends in positive drug tests, United States Air Force, fiscal years 1997-1999.  

PubMed

We investigated the relationship between various demographic factors and the risk of testing positive for marijuana or cocaine use in the U.S. Air Force in fiscal years 1997 through 1999. Overall test positive rates for marijuana and cocaine were very low, at 0.24 and 0.07% of all tests, respectively. However, monthly test positive rates increased significantly during the study period while the number of tests conducted decreased by more than 50%. Gender, race/ethnicity, service component, military rank, education level, and assignment location each predicted the likelihood of testing positive for marijuana or cocaine use. These findings were consistent with annual surveys of self-reported drug use conducted in military and civilian populations in the United States. We conclude that overall testing percentages should be re-evaluated in light of these findings, but we do not recommend oversampling from population subgroups that demonstrated a higher likelihood of testing positive. PMID:15291178

Grayson, J Kevin; Gibson, Roger L; Shanklin, Shari L; Neuhauser, Katerina M; McGhee, Charles

2004-07-01

68

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

PubMed Central

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

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

2015-01-01

69

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

PubMed Central

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

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

2013-01-01

70

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

PubMed

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

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

2012-08-01

71

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

PubMed

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

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

2015-01-01

72

Environmental and biological monitoring of platinum-containing drugs in two hospital pharmacies using positive air pressure isolators.  

PubMed

Environmental and biological monitoring of platinum containing drugs was implemented in two French hospital pharmacies using positive air pressure isolators and having similar working procedures when preparing antineoplastic drugs. Wipe sampling of surfaces, gloves, and vials was performed in the preparation room and in storage areas. All employees involved in the preparation of antineoplastic drugs were tested for urinary platinum on Monday before work and Friday after shift. Only traces of platinum were detected on surfaces in the preparation room outside the isolators (less than 1.61 pg cm(-2)). However, in one center, significant contamination was found in the storage area of the drug vials, which can most likely be linked to the rupture of a platinum vial and due to inefficient cleaning procedures. Surfaces inside the isolators were found to be contaminated (maximum: 198.4 pg cm(-2)). A higher level of contamination was detected in one pharmacy and could be explained by the lack of overgloving with regular changes during the preparation process. Nitrile gloves used during drug handling outside the isolator showed the highest platinum concentration (maximum: 5.86 ng per pair). With regards to platinum urine concentration, no significant difference was found between exposed and unexposed pharmacy personnel. Isolator technology combined with individual protective measures seems to be efficient to protect workers from occupational exposure to antineoplastic drugs, whereas specific individual protective procedures implemented were focussing on the risk of handling vials outside the isolator (e.g. high frequency of glove changing). Moreover, overgloving inside the isolator would contribute to substantially decrease inner surface contamination and should be recommended in order to limit the transfer of chemical contamination to the end products. PMID:23091112

Kopp, Bettina; Crauste-Manciet, Sylvie; Guibert, Agnès; Mourier, Wilhelmine; Guerrault-Moro, Marie-Noelle; Ferrari, Sylvie; Jomier, Jean-Yves; Brossard, Denis; Schierl, Rudolf

2013-04-01

73

Computational modeling of drug distribution in the posterior segment of the eye: effects of device variables and positions.  

PubMed

A computational model was developed to simulate drug distribution in the posterior segment of the eye after intravitreal injection and ocular implantation. The effects of important factors in intravitreal injection such as injection time, needle gauge and needle angle on the ocular drug distribution were studied. Also, the influences of the position and the type of implant on the concentration profile in the posterior segment were investigated. Computational Fluid Dynamics (CFD) calculations were conducted to describe the 3D convective-diffusive transport. The geometrical model was constructed based on the human eye dimensions. To simulate intravitreal injection, unlike previous studies which considered the initial shape of the injected drug solution as a sphere or cylinder, the more accurate shape was obtained by level-set method in COMSOL. The results showed that in intravitreal injection the drug concentration profile and its maximum value depended on the injection time, needle gauge and penetration angle of the needle. Considering the actual shape of the injected solution was found necessary to obtain the real concentration profile. In implant insertion, the vitreous cavity received more drugs after intraocular implantation, but this method was more invasive compared to the periocular delivery. Locating the implant in posterior or anterior regions had a significant effect on local drug concentrations. Also, the shape of implant influenced on concentration profile inside the eye. The presented model is useful for optimizing the administration variables to ensure optimum therapeutic benefits. Predicting and quantifying different factors help to reduce the possibility of tissue toxicity and to improve the treatment efficiency. PMID:24946303

Jooybar, Elaheh; Abdekhodaie, Mohammad J; Farhadi, Fatolla; Cheng, Yu-Ling

2014-09-01

74

Challenges facing HIV-positive persons who use drugs and their families in Vietnam.  

PubMed

It is hypothesized that persons who use drugs (PWUD) in Vietnam who are also HIV-positive may face additional challenges in psychosocial outcomes, and these challenges may extend to their family members. In this study, we examined depressive symptoms, stigma, social support, and caregiver burden of HIV-positive PWUD and their family members, compared to the outcomes of HIV-negative PWUD and their family members. Baseline, 3-month, and 6-month assessment data were gathered from 83 PWUD and 83 family members recruited from four communes in Phú Th? Province, Vietnam. For PWUD, although we observed a general decline in overall stigma over time for both groups, HIV-positive PWUD consistently reported significantly higher overall stigma for all three periods. Depressive symptoms among family members in both groups declined over time; however, family members of HIV-positive PWUD reported higher depressive symptoms across all three periods. In addition, family members of HIV-positive PWUD reported lower levels of tangible support across all three periods. Caregiver burden among family members of HIV-positive PWUD increased significantly over time, whereas the reported burden among family members of HIV-negative PWUD remained relatively unchanged. The findings highlight the need for future interventions for PWUD and family members, with targeted and culturally specific strategies to focus on the importance of addressing additional stigma experienced by PWUD who are HIV-positive. Such challenges may have direct negative impact on their family members' depressive symptoms, tangible support, and caregiver burden. PMID:25285396

Lee, Sung-Jae; Li, Li; Lin, Chunqing; Tuan, Le Anh

2015-03-01

75

Molecular characterization of Iranian wheat stripe virus shows its taxonomic position as a distinct species in the genus Tenuivirus.  

PubMed

The full lengths of three genome segments of Iranian wheat stripe virus (IWSV) were amplified by reverse transcription (RT) followed by polymerase chain reaction (PCR) using a primer complementary to tenuivirus conserved terminal sequences. The segments were sequenced and found to comprise 3469, 2337, and 1831 nt, respectively. The gene organization of these segments is similar to that of other known tenuiviruses, each displaying an ambisense coding strategy. IWSV segments, however, are different from those of other viruses with respect to the number of nucleotides and deduced amino acid sequence for each ORF. Depending on the segment, the first 16-22 nt at the 5' end and the first 16 nt at the 3' end are highly conserved among IWSV and rice hoja blanca virus (RHBV), rice stripe virus (RSV) and maize stripe virus (MStV). In addition, the first 15-18 nt at the 5' end are complementary to the first 16-18 nt at the 3' end. Phylogenetic analyses showed close similarity and a common ancestor for IWSV, RHBV, and Echinochloa hoja blanca virus (EHBV). These findings confirm the position of IWSV as a distinct species in the genus Tenuivirus. PMID:16328148

Heydarnejad, J; Barclay, W S; Izadpanah, K; Hunter, F R; Gooding, M J

2006-02-01

76

Research from UCLA and Vanderbilt shows that new melanoma drug nearly doubles survival in majority of patients  

Cancer.gov

Investigators from Vanderbilt-Ingram Cancer Center, UCLA and 11 other centers in the United States and Australia have found that a new drug for patients with metastatic melanoma nearly doubled median overall survival

77

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

PubMed

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

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

2015-02-01

78

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

PubMed Central

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

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

2012-01-01

79

Microfluidic Technique to Measure Intratumoral Transport and Calculate Drug Efficacy Shows that Binding is Essential for Doxorubicin and Release Hampers Doxil  

PubMed Central

Intratumoral transport and binding are important mechanisms that determine the efficacy of cancer drugs. Current drug screening methods rely heavily on monolayers of cancer cells, which overlook the contribution of tissue-level transport and binding. To quantify these factors, we developed a method that couples an in vitro, drug-delivery device containing a three-dimensional cell mass and a mathematical model of drug diffusion, binding to DNA, release from carriers, and clearance. Spheroids derived from LS174T human colon carcinoma cells were inserted into rectangular chambers to form rectangular cell masses (tissue) and subjected to continuous medium perfusion. To simulate drug delivery and clearance, the tissues were treated with doxorubicin followed by drug-free medium. To evaluate the effect of liposome encapsulation, tissues were treated with liposome-encapsulated doxorubicin (Doxil). Spatiotemporal dynamics of drug distribution and apoptosis was measured by fluorescence microscopy. The diffusivity and DNA binding constant of doxorubicin were determined by fitting experimental data to the mathematical model. Results show that an ideal combination of diffusivity, binding constant, clearance rate, and cytotoxicity contribute to the high therapeutic efficacy of doxorubicin. There was no detectable release of doxorubicin from Doxil in the tissues. The rate of doxorubicin release, evaluated by fitting experimental data to the mathematical model, was below therapeutically effective levels. These results show that despite enhanced systemic circulation obtained by liposome encapsulation, the therapeutic effect of Doxil is limited by slow intratumoral drug release. The experimental and computational methods developed here to calculate drug efficacy provide mechanisms to explain poor performance of drug candidates, and enable design of more successful cancer drugs. PMID:23860772

Toley, Bhushan J.; Lovatt, Zachary Tropeano; Harrington, Josephine L.; Forbes, Neil S.

2013-01-01

80

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

PubMed Central

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

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

2014-01-01

81

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

ERIC Educational Resources Information Center

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

Copeland, Lorraine

2004-01-01

82

Dana-Farber study shows promise of hormone-depleting drug against localized high-risk prostate tumors  

Cancer.gov

A hormone-depleting drug approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5 in Chicago. The phase II clinical trial, led by investigators at Dana-Farber Cancer Institute and other research centers, examined the use of the drug abiraterone acetate (Zytiga) in combination with prednisone and surgery in 58 men with high-risk prostate cancer isolated to the prostate gland.

83

Penn study shows that HIV drug reduces graft-versus-host disease in stem cell transplant patients:  

Cancer.gov

An HIV drug that redirects immune cell traffic appears to significantly reduce the dangerous complication graft-versus-host disease in blood cancer patients following allogeneic stem cell transplantation, according to new research from the Perelman School of Medicine at the University of Pennsylvania that will be presented today at the 53rd American Society of Hematology Annual Meeting.

84

U of Michigan researchers find that Naproxen plus acid blocking drug shows promise in preventing bladder cancer  

Cancer.gov

The anti-inflammatory class of drugs NSAIDs have shown great promise in preventing cancers including colon, esophagus and skin. However, they can increase the risks of heart attacks, ulcers and rare but potentially life-threatening bleeds. A new study suggests there may be ways to reduce these dangerous side effects.

85

MD Anderson study shows targeted agent addition to herceptin has positive effect on metastatic HER-2 breast cancer:  

Cancer.gov

Adding Afinitor (everolimus) to Herceptin (trastuzumab), the main treatment for HER2-positive metastatic breast cancer, helps some women with disease that has been resistant to previous Herceptin-based therapies, according to a study led by researchers at The University of Texas MD Anderson Cancer Center and published in the Journal of Clinical Oncology.

86

Plasmodium falciparum field isolates from areas of repeated emergence of drug resistant malaria show no evidence of hypermutator phenotype.  

PubMed

Multiple transcontinental waves of drug resistance in Plasmodium falciparum have originated in Southeast Asia before spreading westward, first into the rest of Asia and then to sub-Saharan Africa. In vitro studies have suggested that hypermutator P. falciparum parasites may exist in Southeast Asia and that an increased rate of acquisition of new mutations in these parasites may explain the repeated emergence of drug resistance in Southeast Asia. This study is the first to test the hypermutator hypothesis using field isolates. Using genome-wide SNP data from human P. falciparum infections in Southeast Asia and West Africa and a test for relative rate differences we found no evidence of increased relative substitution rates in P. falciparum isolates from Southeast Asia. Instead, we found significantly increased substitution rates in Mali and Bangladesh populations relative to those in populations from Southeast Asia. Additionally we found no association between increased relative substitution rates and parasite clearance following treatment with artemisinin derivatives. PMID:25514047

Brown, Tyler S; Jacob, Christopher G; Silva, Joana C; Takala-Harrison, Shannon; Djimdé, Abdoulaye; Dondorp, Arjen M; Fukuda, Mark; Noedl, Harald; Nyunt, Myaing Myaing; Kyaw, Myat Phone; Mayxay, Mayfong; Hien, Tran Tinh; Plowe, Christopher V; Cummings, Michael P

2015-03-01

87

Cold Spring Harbor live imaging shows response to cancer drugs can be boosted by altering tumor microenvironment  

Cancer.gov

In research published online in the journal Cancer Cell, a team reports using “live” microscopy to observe how cancer cells in mouse tumors react to the widely used chemotherapeutic agent doxorubicin. They found that selective inhibition of two factors that regulate the tumor microenvironment -- enzymes called matrix metalloproteinases (MMPs) and a class of immune signaling molecules called chemokines -- made breast tumors in mice more responsive to the drug.

88

Role of Catheter's Position for Final Results in Intrathecal Drug Delivery. Analysis Based on CSF Dynamics and Specific Drugs Profiles  

PubMed Central

Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy. PMID:24155999

Luciano, Perotti; Vicente, Villanueva; Juan Marcos, Asensio Samper; Gustavo, Fabregat-Cid

2013-01-01

89

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

PubMed Central

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

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

2014-01-01

90

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

PubMed Central

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

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

2015-01-01

91

Aggressive behaviors in the adolescent children of HIV-positive and HIV-negative drug-abusing fathers.  

PubMed

This study examined aggressive behaviors in the adolescent children of HIV-positive and HIV-negative drug-abusing fathers. Data were collected via individual structured interviews of low-income, predominantly African American and Hispanic, father-child dyads (N = 415). Structural Equation Modeling was used to assess the interrelationship of several latent constructs with respect to adolescent aggression. Results showed a mediational model linking paternal attributes (including HIV status) and ecological factors with the father-child relationship, which impacted peer influences and the adolescent's vulnerable personality, which was the most proximal construct to aggressive behaviors. Ecological factors were also mediated by peer influences and directly linked with adolescent aggression. PMID:16864470

Brook, David W; Brook, Judith S; Rubenstone, Elizabeth; Zhang, Chenshu

2006-01-01

92

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

PubMed Central

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

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

2015-01-01

93

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2014 CFR

...positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result or has a confirmed alcohol test result of 0.04 or greater,...

2014-10-01

94

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2010 CFR

...positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result or has a confirmed alcohol test result of 0.04 or greater,...

2010-10-01

95

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2012 CFR

...positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result or has a confirmed alcohol test result of 0.04 or greater,...

2012-10-01

96

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2013 CFR

...positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result or has a confirmed alcohol test result of 0.04 or greater,...

2013-10-01

97

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...  

Code of Federal Regulations, 2011 CFR

...positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result or has a confirmed alcohol test result of 0.04 or greater,...

2011-10-01

98

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...  

Code of Federal Regulations, 2010 CFR

...positive drug test result and/or breath alcohol test result of 0.04 or greater. 655...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result and/or breath alcohol test result of 0.04 or greater....

2010-10-01

99

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...  

Code of Federal Regulations, 2014 CFR

...positive drug test result and/or breath alcohol test result of 0.04 or greater. 655...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result and/or breath alcohol test result of 0.04 or greater....

2014-10-01

100

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...  

Code of Federal Regulations, 2011 CFR

...positive drug test result and/or breath alcohol test result of 0.04 or greater. 655...DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT...positive drug test result and/or breath alcohol test result of 0.04 or greater....

2011-10-01

101

Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon.  

PubMed

Candida species are a common cause of infection in immune-compromised HIV-positive individuals, who are usually treated with the antifungal drug, fluconazole, in public hospitals in Africa. However, information about the prevalence of drug resistance to fluconazole and other antifungal agents on Candida species is very limited. This study examined 128 Candida isolates from South Africa and 126 Cameroonian Candida isolates for determination of species prevalence and antifungal drug susceptibility. The isolates were characterized by growth on chromogenic and selective media and by their susceptibility to 9 antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific, USA). Eighty-three percent (82.8%) of South African isolates were Candida albicans (106 isolates), 9.4% were Candida glabrata (12 isolates), and 7.8% were Candida dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% Candida tropicalis (4 isolates); 2.4% Candida krusei (3 isolates); 1.59% either Candida kefyr, Candida parapsilopsis, or Candida lusitaneae (2 isolates); and 0.79% C. dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was detected phenotypically in both populations. Differences in drug resistance were seen within C. glabrata found in both populations. Echinocandin drugs were more effective on isolates obtained from the Cameroon than in South Africa. A multiple-drug resistant C. dubliniensis strain isolated from the South African samples was inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among oral Candida species is common among African HIV patients in these 2 countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients. PMID:24726686

Dos Santos Abrantes, Pedro Miguel; McArthur, Carole P; Africa, Charlene Wilma Joyce

2014-06-01

102

A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent  

PubMed Central

Conditional gene inactivation using the Cre/loxP system is widely used, but the difficulty in properly regulating Cre expression remains one of the bottlenecks. One approach to regulate Cre activity utilizes a mutant estrogen hormone-binding domain (ERT) to keep Cre inactive unless the non-steroidal estrogen analog 4-hydroxytamoxifen (OHT) is present. Here we describe a mouse strain expressing Cre-ERT from the ubiquitously expressed ROSA26 (R26) locus. We demonstrate efficient temporal and spatial regulation of Cre recombination in vivo and in primary cells derived from these mice. We show the existence of marked differences in recombination frequencies between different substrates within the same cell. This has important consequences when concurrent switching of multiple alleles within the same cell is needed, and highlights one of the difficulties that may be encountered when using reporter mice as indicator strains. PMID:11306549

Vooijs, Marc; Jonkers, Jos; Berns, Anton

2001-01-01

103

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

PubMed Central

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

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

2009-01-01

104

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

PubMed

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

Prasad, Dev; Chauhan, Harsh; Atef, Eman

2014-11-01

105

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

PubMed Central

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

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

2014-01-01

106

Complications of open reduction and internal fixation of ankle fractures in patients with positive urine drug screen.  

PubMed

We conducted a study to identify complications associated with open treatment of ankle fractures in patients who tested positive for illicit drugs on urine drug screen (UDS). We hypothesized that patients who had a history of positive UDS and underwent open reduction and internal fixation of an ankle fracture would have a higher incidence of major and minor complications. We retrospectively reviewed the cases of 142 patients who had surgical stabilization of an ankle fracture during a 3-year period. Patients with a history of positive UDS were compared with matched controls with negative UDS. Outcomes measures included nonunion, malunion, and superficial or deep infection. Fisher exact test, Wilcoxon rank sum test, and univariate logistic regression were used to determine statistical significance. There were no significant differences in age, sex, fracture type, incidence of diabetes, or incidence of open fracture between the groups. Incidence of nonunion was higher in patients with positive UDS (P = .01), as was incidence of deep infection (P = .05). Incidence of pooled major complications was also higher in positive UDS patients (P = .03). Patients with a history of illicit drug use, as evidenced by positive UDS, are at increased risk for perioperative complications during treatment for ankle fracture. PMID:25750944

Saldanha, Vilas; Tiedeken, Nathan; Gaughan, John; Sweitzer, Brett A

2015-03-01

107

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

Microsoft Academic Search

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

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

2003-01-01

108

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

PubMed

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

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

2015-01-30

109

Drug testing welfare recipients--false positives, false negatives, unanticipated opportunities.  

PubMed

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. PMID:11786289

Pollack, Harold A; Danziger, Sheldon; Jayakody, Rukmalie; Seefeldt, Kristin S

2002-01-01

110

Peptide-MHC heterodimers show that thymic positive selection requires a more restricted set of self-peptides than negative selection  

PubMed Central

T cell selection and maturation in the thymus depends on the interactions between T cell receptors (TCRs) and different self-peptide–major histocompatibility complex (pMHC) molecules. We show that the affinity of the OT-I TCR for its endogenous positively selecting ligands, Catnb-H-2Kb and Cappa1-H-2Kb, is significantly lower than for previously reported positively selecting altered peptide ligands. To understand how these extremely weak endogenous ligands produce signals in maturing thymocytes, we generated soluble monomeric and dimeric peptide–H-2Kb ligands. Soluble monomeric ovalbumin (OVA)-Kb molecules elicited no detectable signaling in OT-I thymocytes, whereas heterodimers of OVA-Kb paired with positively selecting or nonselecting endogenous peptides, but not an engineered null peptide, induced deletion. In contrast, dimer-induced positive selection was much more sensitive to the identity of the partner peptide. Catnb-Kb–Catnb-Kb homodimers, but not heterodimers of Catnb-Kb paired with a nonselecting peptide-Kb, induced positive selection, even though both ligands bind the OT-I TCR with detectable affinity. Thus, both positive and negative selection can be driven by dimeric but not monomeric ligands. In addition, positive selection has much more stringent requirements for the partner self-pMHC. PMID:20457759

Juang, Jeremy; Ebert, Peter J.R.; Feng, Dan; Garcia, K. Christopher; Krogsgaard, Michelle

2010-01-01

111

Blood as the earliest drug, its substitutes, preparations and latest position.  

PubMed

Blood was soul and Redness its active principle when red substances were rich in soul-content. But soul was a substance whence blood became a drug which donated soul to treat wounds and incurable diseases. Its redness as life-force, but also as substance, could prolong life. A drug made from human blood could treat serious wounds and as a life saving drug was also a drug of fertility. The latest use of blood appears as syrup haemoglobin while the latest use of human blood would be blood transfusion. PMID:3541572

Mahdihassan, S

1986-01-01

112

Drug testing welfare recipients—false positives, false negatives, unanticipated opportunities  

Microsoft Academic Search

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

Harold A Pollack; Sheldon Danziger; Rukmalie Jayakody; Kristin S Seefeldt

2002-01-01

113

Risk factors for distress in the adolescent children of HIV-positive and HIV-negative drug-abusing fathers.  

PubMed

In contrast to previous research on parental drug abuse, the present study examined comorbid drug addiction and HIV infection in the father as related to his adolescent child's psychological distress. Individual structured interviews were administered to 505 HIV-positive and HIV-negative drug-abusing fathers and one of their children, aged 12-20. Structural equation modelling tested an hypothesized model linking paternal latent variables, ecological factors and adolescent substance use to adolescent distress. Results demonstrated a direct pathway between paternal distress and adolescent distress, as well as an indirect pathway; namely, paternal distress was linked with impaired paternal teaching of coping skills to the child, which in turn was related to adolescent substance use and, ultimately, to the adolescent's distress. There was also an association between paternal drug addiction/HIV and adolescent distress, which was mediated by both ecological factors and adolescent substance use. Findings suggest an increased risk of distress in the adolescent children of fathers with comorbid drug addiction and HIV/AIDS, which may be further complicated by paternal distress. Results suggest several opportunities for prevention and treatment programmes for the children of drug-abusing fathers. PMID:18278619

Brook, D W; Brook, J S; Rubenstone, E; Zhang, C; Castro, F G; Tiburcio, N

2008-01-01

114

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

PubMed

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

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

2014-05-01

115

Media's Positive and Negative Frames in Reporting Celebrity Deaths From Illegal Drug Overdoses Versus Prescription Drug Overdoses  

E-print Network

the majority of participants in that study reported that their idols were a positive influence, an overriding concern in this field is that celebrities can act as advocates for undesirable behaviors (Shaw et al., 2010). Additionally, the International Narcotics... family (Gibson, 2007; Kearl, 2011; Terry, 1999). With increasing media platforms for people to interact with celebrities, fans can now, more than ever before, feel a sense of intimacy with their idols. It is also ironic that, just as audiences come...

Wood, Michelle

2011-12-31

116

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

SciTech Connect

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

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

2013-10-15

117

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

PubMed Central

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

2014-01-01

118

[Positioning of autoPBSCT in the treatment of multiple myeloma in the era of new drugs].  

PubMed

At present, a standard therapy for de novo multiple myeloma (MM) patients under 65 years old without severe comorbidity is an upfront high dose chemotherapy (HDCT) with MEL200 combined with auto peripheral blood stem cell transplantation (autoPBSCT) after the induction therapy. However, three-drug regimens including new drugs such as bortezomib (Bor) and lenalidomide (Len) have been shown to achieve deep molecular responses as an induction therapy for de novo MM patients. Several phase II studies using RVD (Len, Bor, dexamethasone) or CRd (carfilzomib, Len, dexamethasone) showed very promising data, suggesting that the continuance of these regimens might be able to substitute HDCT. In contrast, early HDCT was shown to be better than late HDCT in another trials. So, the upfront autoPBSCT is still needed even in the era of new drugs. However, future prospective phase III randomized trials using new drugs such as carfilzomib and ponalidomide might rewrite the present evidence. PMID:25626309

Matsumura, Itaru

2015-01-01

119

Lack of cross-resistance to fostriecin in a human small-cell lung carcinoma cell line showing topoisomerase II-related drug resistance  

Microsoft Academic Search

Cells exhibiting decreased topoisomerase II (Topo II) activity are resistant to several drugs that require Topo II as an intermediate. These drugs are cytotoxic due to the formation of a cleavable complex between the drug, Topo II and DNA. Fostriecin belongs to a new class of drugs that inhibit Topo II without inducing the formation of this cleavable complex. We

Steven de Jong; Jan G. Zijlstra; Nanno H. Mulder; Elisabeth G. E. de Vries

1991-01-01

120

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

E-print Network

, vancomycin-resistant Enterococcus faecalis (VRE), and two Gram-negative bacterial species. At least 20- resistant isolates of Enterococcus species (VRE), nosoco- mial pathogenic species with frequent multi-drug resistance to other agents such as ampicillin and amino- glycosides. Over 28% of Enterococcus spp

Nizet, Victor

121

Can Supply Restrictions Lower Price? Violence, Drug Dealing and Positional Advantage  

Microsoft Academic Search

The standard model of markets for illicit drugs predicts that tougher enforcement against sellers will raise prices; yet cocaine and heroin prices have fallen substantially during a period of massive increases in enforcement. We present a model in which the basic mechanisms at work in the textbook model may be substantially altered by an important feature of illegal markets—violence that

Jonathan P. Caulkins; Peter Reuter; Lowell J. Taylor

2006-01-01

122

Estrogen receptor positive breast cancer identified by 95-gene classifier as at high risk for relapse shows better response to neoadjuvant chemotherapy.  

PubMed

A 95-gene classifier (95-GC) recently developed by us can predict the risk of relapse for ER-positive and node-negative breast cancer patients with high accuracy. This study investigated association of risk classification by 95-GC with response to neoadjuvant chemotherapy (NAC). Tumor biopsy samples obtained preoperatively from 72 patients with ER-positive breast cancer were classified by 95-GC into high-risk and low-risk for relapse. Pathological complete response (pCR) rate was numerically higher for high-risk (15.8%) than low-risk patients (8.8%) although the difference was not statistically significant. Pathological response evaluated in terms of the pathological partial response (pPR) rate (loss of tumor cells in more than two-thirds of the primary tumor) showed a significant association (P=0.005) between the high-risk patients and a high pPR rate. Besides, external validation study using the public data base (GSE25066) showed that the pCR rate (16.4%) for high-risk patients (n=128) was significantly (P=0.003) higher than for low-risk patients (5.7%) (n=159). These results demonstrate that the high-risk patients for relapse show a higher sensitivity to chemotherapy and thus are likely to benefit more from adjuvant chemotherapy. PMID:22546287

Tsunashima, Ryo; Naoi, Yasuto; Kishi, Kazuki; Baba, Yosuke; Shimomura, Atsushi; Maruyama, Naomi; Nakayama, Takahiro; Shimazu, Kenzo; Kim, Seung Jin; Tamaki, Yasuhiro; Noguchi, Shinzaburo

2012-11-01

123

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

Code of Federal Regulations, 2010 CFR

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

2010-01-01

124

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

Code of Federal Regulations, 2011 CFR

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

2011-01-01

125

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

Code of Federal Regulations, 2014 CFR

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

2014-01-01

126

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

Code of Federal Regulations, 2013 CFR

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

2013-01-01

127

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

Code of Federal Regulations, 2012 CFR

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

2012-01-01

128

UNC researchers find new approach to treat drug-resistant HER2-positive breast cancer  

Cancer.gov

Using human cancer cell lines, scientists identified various ways that HER2-positive breast cancer tumors resist therapy, and they discovered a potential combination therapy to overcome multiple mechanisms of resistance and kill cancer cells.

129

Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders.  

PubMed

Antiepileptic drugs (AEDs) have various mechanisms of actions and therefore have diverse anticonvulsant, psychiatric, and adverse effect profiles. Two global categories of AEDs are identified on the basis of their predominant psychotropic profiles. One group has "sedating" effects in association with fatigue, cognitive slowing, and weight gain, as well as possible anxiolytic and antimanic effects. These actions may be related to a predominance of potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission induced by drugs such as barbiturates, benzodiazepines, valproate, gabapentin, tiagabine, and vigabatrin. The other group is associated with predominant attenuation of glutamate excitatory neurotransmission and has "activating" effects, with activation, weight loss, and possibly anxiogenic and antidepressant effects. This group includes agents such as felbamate and lamotrigine. Agents such as topiramate, with both GABAergic and antiglutamatergic actions, may have "mixed" profiles. Mechanisms of actions, activity in animal models of anxiety and depression, and clinical psychotropic effects of AEDs in psychiatric and epilepsy patients are reviewed in relationship to this proposed categorization. These considerations suggest the testable hypothesis that better psychiatric outcomes in seizure disorder patients could be achieved by treating patients with baseline "activated" profiles (insomnia, agitation, anxiety, racing thoughts, weight loss) with "sedating" predominantly GABAergic drugs, and conversely those with baseline "sedated" or anergic profiles (hypersomnia, fatigue, apathy, depression, sluggish cognition, weight gain) with "activating" predominantly antiglutamatergic agents. Systematic clinical investigation of more precise relationships of discrete mechanisms of actions to psychotropic profiles of AEDs is needed to assess the utility of this general proposition and define exceptions to this broad principle. PMID:10496235

Ketter, T A; Post, R M; Theodore, W H

1999-01-01

130

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

Microsoft Academic Search

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

Lamei Chen; Alla Perlina; Christopher J. Lee

2004-01-01

131

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

PubMed

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

Neale, Joanne; Stevenson, Caral

2014-10-01

132

Recurrent major depressive disorder among human immunodeficiency virus (HIV)-positive and HIV-negative intravenous drug users: Findings of a 3-year longitudinal study  

Microsoft Academic Search

A longitudinal study was conducted to investigate the association between human immunodeficiency virus (HIV) infection, history of major depressive disorder (MDD), and persistent or recurrent MDD among intravenous drug users. Psychiatric disorders were assessed in a sample of HIV-positive (HIV+) and HIV-negative (HIV?) intravenous drug users every 6 months for 3 years. Results indicated that HIV status and baseline MDD

Jeffrey G Johnson; Judith G Rabkin; Joshua D Lipsitz; Janet B. W Williams; Robert H Remien

1999-01-01

133

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

PubMed Central

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

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

2009-01-01

134

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

E-print Network

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

Pillow, Jonathan

135

Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier.  

PubMed

A novel functionalised copolymer with three polymeric components, poly(ethylene glycol)-block-poly(aspartic acid-stat-phenylalanine), PEG-P(asp-phe), was synthesised and investigated for its potential to form micelles via ionic interactions with a model water-soluble drug, diminazene aceturate. Drug-free solutions of structurally related PEG-P(asp-phe) 5:6:4 and PEG-P(asp-phe) 5:4:6 copolymers indicated polymeric aggregation into micellar-type constructs. The size of PEG-P(asp-phe) 5:6:4 micelles was found to be pH and drug content-dependent. The drug-loaded systems existed as discreet units and were fairly uniform in size and shape. More drug could be included in the PEG-P(asp-phe) 5:6:4 micelles as compared to if only interaction with carboxyl groups from aspartic acid units was responsible for micelle formation, indicating the augmentative role of phenylalanine moieties in drug-incorporation. The slower in vitro drug release from PEG-P(asp-phe) 5:6:4 micelles as compared to PEG-Pasp (AB) micelles indicated the role of the phenylalanine moiety in controlling drug release. This study, therefore, confirmed the potential of a novel tri-component copolymer structure, PEG-P(asp-phe), for the formation of polyionic micelles for drug delivery. PMID:15907607

Prompruk, K; Govender, T; Zhang, S; Xiong, C D; Stolnik, S

2005-06-13

136

Hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity designed for targeting of CD44-positive and drug-resistant tumors  

PubMed Central

Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we report the synthesis of nanogel-drug conjugates based on membranotropic cholesteryl-HA (CHA) for efficient targeting and suppression of drug-resistant tumors. These conjugates significantly increased the bioavailability of poorly soluble drugs with previously reported activity against CSC, such as etoposide, salinomycin, and curcumin. The small nanogel particles (diam. 20–40 nm) with a hydrophobic core and high drug loads (up to 20%) formed after ultrasonication and demonstrated a sustained drug release following the hydrolysis of biodegradable ester linkage. Importantly, CHA-drug nanogels demonstrated 2–7 times higher cytotoxicity in CD44-expressing drug-resistant human breast and pancreatic adenocarcinoma cells compared to free drugs and non-modified HA-drug conjugates. These nanogels were efficiently internalized via CD44 receptor-mediated endocytosis and simultaneous interaction with the cancer cell membrane. Anchoring by cholesterol moieties in the cellular membrane after nanogel unfolding evidently caused more efficient drug accumulation in cancer cells compared to non-modified HA-drug conjugates. CHA-drug nanogels were able to penetrate multicellular cancer spheroids and displayed higher cytotoxic effect in the system modeling tumor environment than both free drugs and HA-drug conjugates. In conclusion, the proposed design of nanogel-drug conjugates allowed us to significantly enhance drug bioavailability, cancer cell targeting, and the treatment efficacy against drug-resistant cancer cells and multicellular spheroids. PMID:23547842

Wei, Xin; Senanayake, Thulani H.; Warren, Galya; Vinogradov, Serguei V.

2013-01-01

137

Hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity designed for the targeting of CD44-positive and drug-resistant tumors.  

PubMed

Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we report the synthesis of nanogel-drug conjugates based on membranotropic cholesteryl-HA (CHA) for efficient targeting and suppression of drug-resistant tumors. These conjugates significantly increased the bioavailability of poorly soluble drugs with previously reported activity against CSC, such as etoposide, salinomycin, and curcumin. The small nanogel particles (diameter 20-40 nm) with a hydrophobic core and high drug loads (up to 20%) formed after ultrasonication and demonstrated a sustained drug release following the hydrolysis of biodegradable ester linkage. Importantly, CHA-drug nanogels demonstrated 2-7 times higher cytotoxicity in CD44-expressing drug-resistant human breast and pancreatic adenocarcinoma cells compared to that of free drugs and nonmodified HA-drug conjugates. These nanogels were efficiently internalized via CD44 receptor-mediated endocytosis and simultaneous interaction with the cancer cell membrane. Anchoring by cholesterol moieties in the cellular membrane after nanogel unfolding evidently caused more efficient drug accumulation in cancer cells compared to that in nonmodified HA-drug conjugates. CHA-drug nanogels were able to penetrate multicellular cancer spheroids and displayed a higher cytotoxic effect in the system modeling tumor environment than both free drugs and HA-drug conjugates. In conclusion, the proposed design of nanogel-drug conjugates allowed us to significantly enhance drug bioavailability, cancer cell targeting, and the treatment efficacy against drug-resistant cancer cells and multicellular spheroids. PMID:23547842

Wei, Xin; Senanayake, Thulani H; Warren, Galya; Vinogradov, Serguei V

2013-04-17

138

Forfeiture of illegally acquired assets of drug traffickers: the position in India.  

PubMed

Trafficking in drugs and other related crimes generates huge illicit funds which are used to support other criminal activity, corruption, illicit arms trading, the smuggling of goods and currency, and other economic offences. The traditional enforcement techniques aimed only at carriers and confiscation of the seized contraband no longer provide a sufficient deterrent. The problem is international in scope and requires close cooperation of all the agencies concerned. In 1976, India enacted specific legislation providing for the forfeiture of the property and assets of smugglers, including traffickers and foreign-exchange manipulators. This legislation, known as the "Smugglers and Foreign-Exchange Manipulators (Forfeiture of Property) Act, 1976", enables the enforcement authorities to confiscate all property, both movable and immovable, illegally acquired or accumulated, or for which investment is made from unlawful earnings resulting from smuggling and foreign exchange racketeering. It covers all such property held, not only in the names of smugglers and traffickers themselves, but their relatives and associates as well. The Act provides for principles of natural justice to be followed for all forfeiture proceedings and for appeals to a high tribunal. The legislation has enabled forfeiture action in 2,297 cases, covering properties valued at $US 40 million, during the last six years. PMID:6556075

Gujral, B B

1983-01-01

139

EMERGENCY DEPARTMENT UTILIZATION AMONG A COHORT OF HIV-POSITIVE INJECTING DRUG USERS IN A CANADIAN SETTING  

PubMed Central

Background HIV-positive injection drug users (IDU) are known to be at risk for multiple medical problems that may necessitate emergency department (ED) use, however, the relative contribution of HIV disease versus injection-related complications have not been well described. Objectives We examined factors associated with ED use among a prospective cohort of HIV-positive IDU in a Canadian setting. Methods We enrolled HIV-positive IDU into a community-recruited prospective cohort study. We modeled factors associated with the time to first ED visit using Cox regression to determine factors independently associated with ED use. In sub-analyses, we examined ED diagnoses and subsequent hospital admission rates. Results Between December 5, 2005, and April 30, 2008, 428 HIV-positive IDU were enrolled, among whom the cumulative incidence of ED use was 63.7% (95% Confidence Interval [CI]: 59.1% – 68.3%) at 12 months after enrollment. Factors independently associated with time to first ED visit included: unstable housing (Hazard Ratio [HR] = 1.5, 95% CI: 1.1–2.0) and reporting being unable to obtain needed health care services (HR = 2.2, 95% CI: 1.2–4.1), whereas CD4 count and viral load were non-significant. Skin and soft tissue infections (SSTIs) accounted for the greatest proportion of ED visits (17%). Of the 2461 visits to the ED, 419 (17%) were admitted to hospital. Conclusions High rates of ED use were observed among HIV-positive IDU, a behavior that was predicted by unstable housing and limited access to primary care. Factors other than HIV infection appear to be driving ED use among this population in the post-HAART era. PMID:21719229

Fairbairn, Nadia; Milloy, M-J; Zhang, Ruth; Lai, Calvin; Grafstein, Eric; Kerr, Thomas; Wood, Evan

2011-01-01

140

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

PubMed Central

Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid "ty-pos OCA" individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8198130

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

1994-01-01

141

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

PubMed Central

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

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

2010-01-01

142

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

Microsoft Academic Search

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

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

1995-01-01

143

Interaction Between Drugs and Biomedical Materials i: Binding Position of Bezafibrate to Human Serum Alubmin  

NASA Astrophysics Data System (ADS)

The interaction between bezafibrate (BZF) and human serum albumin (HSA) was investigated by equilibrium dialysis. Since the binding constant of BZF to HSA was independent of ionic strength and decreased with the addition of fatty acid, the interaction between BZF and HSA was considered to be due to hydrophobic mechanism. Chemical shifts in 1H-NMR spectra of BZF were independent of the concentration of BZF and addition of HSA. Spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) of respective protons of BZF were independent of the concentration, but depended on the concentration of HSA added. The binding position of BZF to HSA was considered to involve the hydrophobic aromatic moiety of BZF from the ratio of spin-spin relaxation rates (1/T2) of BZF bound to HSA and free BZF.

Tanaka, Masami; Minagawa, Keiji; Berber, Mohamed R.; Hafez, Inas H.; Mori, Takeshi

144

Field experiments of Controlled Drainage of agricultural clay soils show positive effects on water quantity (retention, runoff) and water quality (nitrate leaching).  

NASA Astrophysics Data System (ADS)

Despite best management practices, agriculture is still facing major challenges to reduce nutrients leaching to the aquatic environment. In deltas, most of total nutrient losses from artificially drained agricultural soils are discharged via drains. Controlled drainage is a promising measure to prevent drainage of valuable nutrients, improve water quality and agricultural yield and adapt to climate change (reduce peak runoff, manage water scarcity and drought). In The Netherlands, this technique has attracted much attention by water managers and farmers alike, yet field studies to determine the expected (positive) effects for Dutch conditions were scarce. Recently, a field experiment was set up on clay soils. Research questions were: how does controlled, subsurface drainage perform on clay soils? Will deeper tile drains function just as well? What are the effects on drain water quality (especially with respect to nitrogen and salt) and crop yield? An agricultural field on clay soils was used to test different tile drainage configurations. Four types of tile drainage systems were installed, all in duplicate: eight plots in total. Each plot has its own outlet to a control box, where equipment was installed to control drain discharge and to measure the flow, concentrations of macro-ions, pH, nitrogen, N-isotopes and heavy metals. In each plot, groundwater observation wells and suction cups are installed in the saturated and vadose zones, at different depths, and crop yield is determined. Four plots discharge into a hydrologic isolated ditch, enabling the determination of water- and nutrient balances. Automatic drain water samplers and innovative nitrate sensors were installed in four plots. These enable identification and unravelling so-called first flush effects (changes in concentrations after a storm event). Water-, chloride- and nitrogen balances have been set up, and the interaction between groundwater and surface water has been quantified. The hydrological processes in the soil have been modelled with simulation model SWAP. The experiment started in 2010 and is ongoing. Data, collected so far show that the plots with controlled drainage (all compared with plots equipped with conventional drainage) conserve more rain water (higher groundwater tables in early spring), lower discharges under average weather conditions and storm events, reduce N-loads and saline seepage to surface waters, enhance denitrification, show a different 'first flush' effect and show similar crop yields. The results of the experiments will contribute to a better understanding of the impact of controlled drainage on complex hydrological en geochemical processes in agricultural clay soils, the interaction between ground- en surface water and its effects on drain water quantity, quality and crop yield.

schipper, peter; stuyt, lodewijk; straat, van der, andre; schans, van der, martin

2014-05-01

145

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

SciTech Connect

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

Kedda, M.A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M. (South African Institute for Medical Research, Johannesburg (South Africa) Univ. of Witwatersrand, Johannesburg (South Africa))

1994-06-01

146

Surface Proteins of Gram-Positive Pathogens: Using Crystallography to Uncover Novel Features in Drug and Vaccine Candidates  

NASA Astrophysics Data System (ADS)

Proteins displayed on the cell surfaces of pathogenic organisms are the front-line troops of bacterial attack, playing critical roles in colonization, infection and virulence. Although such proteins can often be recognized from genome sequence data, through characteristic sequence motifs, their functions are often unknown. One such group of surface proteins is attached to the cell surface of Gram-positive pathogens through the action of sortase enzymes. Some of these proteins are now known to form pili: long filamentous structures that mediate attachment to human cells. Crystallographic analyses of these and other cell surface proteins have uncovered novel features in their structure, assembly and stability, including the presence of inter- and intramolecular isopeptide crosslinks. This improved understanding of structures on the bacterial cell surface offers opportunities for the development of some new drug targets and for novel approaches to vaccine design.

Baker, Edward N.; Proft, Thomas; Kang, Haejoo

147

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

PubMed Central

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

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

2015-01-01

148

Comparative Transcriptomics of Eastern African Cichlid Fishes Shows Signs of Positive Selection and a Large Contribution of Untranslated Regions to Genetic Diversity  

PubMed Central

The hundreds of endemic species of cichlid fishes in the East African Great Lakes Tanganyika, Malawi, and Victoria are a prime model system in evolutionary biology. With five genomes currently being sequenced, eastern African cichlids also represent a forthcoming genomic model for evolutionary studies of genotype-to-phenotype processes in adaptive radiations. Here we report the functional annotation and comparative analyses of transcriptome data sets for two eastern African cichlid species, Astatotilapia burtoni and Ophthalmotilapia ventralis, representatives of the modern haplochromines and ectodines, respectively. Nearly 647,000 expressed sequence tags were assembled in more than 46,000 contigs for each species using the 454 sequencing technology, largely expanding the current sequence data set publicly available for these cichlids. Total predicted coverage of their proteome diversity is approximately 50% for both species. Comparative qualitative and quantitative analyses show very similar transcriptome data for the two species in terms of both functional annotation and relative abundance of gene ontology terms expressed. Average genetic distance between species is 1.75% when all transcript types are considered including nonannotated sequences, 1.33% for annotated sequences only including untranslated regions, and decreases to nearly half, 0.95%, for coding sequences only, suggesting a large contribution of noncoding regions to their genetic diversity. Comparative analyses across the two species, tilapia and the outgroup medaka based on an overlapping data set of 1,216 genes (?526 kb) demonstrate cichlid-specific signature of disruptive selection and provide a set of candidate genes that are putatively under positive selection. Overall, these data sets offer the genetic platform for future comparative analyses in light of the upcoming genomes for this taxonomic group. PMID:21617250

Baldo, Laura; Santos, M.Emília; Salzburger, Walter

2011-01-01

149

Comparative transcriptomics of Eastern African cichlid fishes shows signs of positive selection and a large contribution of untranslated regions to genetic diversity.  

PubMed

The hundreds of endemic species of cichlid fishes in the East African Great Lakes Tanganyika, Malawi, and Victoria are a prime model system in evolutionary biology. With five genomes currently being sequenced, eastern African cichlids also represent a forthcoming genomic model for evolutionary studies of genotype-to-phenotype processes in adaptive radiations. Here we report the functional annotation and comparative analyses of transcriptome data sets for two eastern African cichlid species, Astatotilapia burtoni and Ophthalmotilapia ventralis, representatives of the modern haplochromines and ectodines, respectively. Nearly 647,000 expressed sequence tags were assembled in more than 46,000 contigs for each species using the 454 sequencing technology, largely expanding the current sequence data set publicly available for these cichlids. Total predicted coverage of their proteome diversity is approximately 50% for both species. Comparative qualitative and quantitative analyses show very similar transcriptome data for the two species in terms of both functional annotation and relative abundance of gene ontology terms expressed. Average genetic distance between species is 1.75% when all transcript types are considered including nonannotated sequences, 1.33% for annotated sequences only including untranslated regions, and decreases to nearly half, 0.95%, for coding sequences only, suggesting a large contribution of noncoding regions to their genetic diversity. Comparative analyses across the two species, tilapia and the outgroup medaka based on an overlapping data set of 1,216 genes (?526 kb) demonstrate cichlid-specific signature of disruptive selection and provide a set of candidate genes that are putatively under positive selection. Overall, these data sets offer the genetic platform for future comparative analyses in light of the upcoming genomes for this taxonomic group. PMID:21617250

Baldo, Laura; Santos, M Emília; Salzburger, Walter

2011-01-01

150

Activity of the novel peptide arminin against multiresistant human pathogens shows the considerable potential of phylogenetically ancient organisms as drug sources.  

PubMed

The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 microM to 0.8 microM). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria. PMID:19770277

Augustin, René; Anton-Erxleben, Friederike; Jungnickel, Stephanie; Hemmrich, Georg; Spudy, Björn; Podschun, Rainer; Bosch, Thomas C G

2009-12-01

151

Activity of the Novel Peptide Arminin against Multiresistant Human Pathogens Shows the Considerable Potential of Phylogenetically Ancient Organisms as Drug Sources?  

PubMed Central

The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 ?M to 0.8 ?M). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria. PMID:19770277

Augustin, René; Anton-Erxleben, Friederike; Jungnickel, Stephanie; Hemmrich, Georg; Spudy, Björn; Podschun, Rainer; Bosch, Thomas C. G.

2009-01-01

152

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

PubMed

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

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

2015-01-01

153

Relationship between Food Insecurity and Mortality among HIV-Positive Injection Drug Users Receiving Antiretroviral Therapy in British Columbia, Canada  

PubMed Central

Objectives Little is known about the potential impact of food insecurity on mortality among people living with HIV/AIDS. We examined the potential relationship between food insecurity and all-cause mortality among HIV-positive injection drug users (IDU) initiating antiretroviral therapy (ART) across British Columbia (BC). Methods Cross-sectional measurement of food security status was taken at participant ART initiation. Participants were prospectively followed from June 1998 to September 2011 within the fully subsidized ART program. Cox proportional hazard models were used to ascertain the association between food insecurity and mortality, controlling for potential confounders. Results Among 254 IDU, 181 (71.3%) were food insecure and 108 (42.5%) were hungry. After 13.3 years of median follow-up, 105 (41.3%) participants died. In multivariate analyses, food insecurity remained significantly associated with mortality (adjusted hazard ratio [AHR]?=?1.95, 95% CI: 1.07–3.53), after adjusting for potential confounders. Conclusions HIV-positive IDU reporting food insecurity were almost twice as likely to die, compared to food secure IDU. Further research is required to understand how and why food insecurity is associated with excess mortality in this population. Public health organizations should evaluate the possible role of food supplementation and socio-structural supports for IDU within harm reduction and HIV treatment programs. PMID:23723968

Anema, Aranka; Chan, Keith; Chen, Yalin; Weiser, Sheri; Montaner, Julio S. G.; Hogg, Robert S.

2013-01-01

154

Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer.  

PubMed

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)-targeted antibody-drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis of T-DM1 in preclinical studies has shown that T-DM1 combines the distinct mechanisms of action of both DM1 and trastuzumab, and has antitumor activity in trastuzumab- and lapatinib-refractory experimental models. Clinically, T-DM1 has a consistent pharmacokinetics profile and minimal systemic exposure to free DM1, with no evidence of DM1 accumulation following repeated T-DM1 doses. Although a few covariates were shown to affect interindividual variability in T-DM1 exposure and clearance in population-pharmacokinetics analyses, the magnitude of their effect on T-DM1 exposure was not clinically relevant. Phase I and phase II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are recruiting patients: EMILIA (NCT00829166) is evaluating T-DM1 compared with lapatinib plus capecitabine, and MARIANNE (NCT01120184) is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Additional combinations of T-DM1 (for example, with GDC-0941) and additional disease settings (early-stage HER2-positive breast cancer) are also under investigation. Data from the phase III trials and other studies of T-DM1-containing agents are eagerly awaited. PMID:22003071

LoRusso, Patricia M; Weiss, Denise; Guardino, Ellie; Girish, Sandhya; Sliwkowski, Mark X

2011-10-15

155

Anti-Tuberculosis Drug Resistance among New and Previously Treated Sputum Smear-Positive Tuberculosis Patients in Uganda: Results of the First National Survey  

PubMed Central

Background Multidrug resistant and extensively drug resistant tuberculosis (TB) have become major threats to control of tuberculosis globally. The rates of anti-TB drug resistance in Uganda are not known. We conducted a national drug resistance survey to investigate the levels and patterns of resistance to first and second line anti-TB drugs among new and previously treated sputum smear-positive TB cases. Methods Sputum samples were collected from a nationally representative sample of new and previously treated sputum smear-positive TB patients registered at TB diagnostic centers during December 2009 to February 2011 using a weighted cluster sampling method. Culture and drug susceptibility testing was performed at the national TB reference laboratory. Results A total of 1537 patients (1397 new and 140 previously treated) were enrolled in the survey from 44 health facilities. HIV test result and complete drug susceptibility testing (DST) results were available for 1524 (96.8%) and 1325 (85.9%) patients, respectively. Of the 1209 isolates from new cases, resistance to any anti-TB drug was 10.3%, 5% were resistant to isoniazid, 1.9% to rifampicin, and 1.4% were multi drug resistant. Among the 116 isolates from previously treated cases, the prevalence of resistance was 25.9%, 23.3%, 12.1% and 12.1% respectively. Of the 1524 patients who had HIV testing 469 (30.7%) tested positive. There was no association between anti-TB drug resistance (including MDR) and HIV infection. Conclusion The prevalence of anti-TB drug resistance among new patients in Uganda is low relative to WHO estimates. The higher levels of MDR-TB (12.1%) and resistance to any drug (25.3%) among previously treated patients raises concerns about the quality of directly observed therapy (DOT) and adherence to treatment. This calls for strengthening existing TB control measures, especially DOT, routine DST among the previously treated TB patients or periodic drug resistance surveys, to prevent and monitor development and transmission of drug resistant TB. PMID:23936467

Lukoye, Deus; Adatu, Francis; Musisi, Kenneth; Kasule, George William; Were, Willy; Odeke, Rosemary; Kalamya, Julius Namonyo; Awor, Ann; Date, Anand; Joloba, Moses L.

2013-01-01

156

Nuclear factor kappa B activation-induced anti-apoptosis renders HER2 positive cells drug resistant and accelerates tumor growth  

PubMed Central

Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2-positive breast cancer, but resistance inevitably occurs. We previously found that nuclear factor kappa B is hyper-activated in a subset of HER-2 positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-?B rendered HER2-positive cancer cells resistant to anti-HER2 drugs and cells selected for Lapatinib resistance up-regulated NF-?B. In both circumstances, cells were anti-apoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-?B inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-?B-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-?B signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-?B activation, and selection for resistance results in NF-?B activation, suggesting this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-?B suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-?B activation. PMID:24319068

Kochupurakkal, Bose; Maulik, Gautam; Rodig, Scott. J.; Tian, Ruiyang; Foley, Kathleen M.; Bowman, Teresa; Miron, Alexander; Brown, Myles

2014-01-01

157

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

E-print Network

flush their expired prescription pain-killers. In each case, traces of these drugs and other pharmachemical compounds can make their way through wastewater treatment facilities and eventually into natural water ways that supply drink- ing water... obscurity to controversy After a decade of researching pharmaceuticals and personal care products (PPCPs) in water and treated wastewater, Dr. Bryan Brooks, professor of environmental science and biomedical studies at Baylor University, has seen...

Jordan, Leslie

2010-01-01

158

Positive Classroom Management. A Step-by-Step Guide to Successfully Running the Show Without Destroying Student Dignity. 2nd Edition.  

ERIC Educational Resources Information Center

This book provides K-12 teachers with concrete, step-by-step guidance on how to improve student behavior through positive classroom management. It explains how to take control of the classroom, offering an alternative to threats, rewards, and punishments. The book is divided into an introduction and three sections with seven chapters. The…

DiGiulio, Robert

159

Acylation of SC4 dodecapeptide increases bactericidal potency against Gram-positive bacteria, including drug-resistant strains  

Microsoft Academic Search

We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal acti- vities of the resultant SC4 'peptide-amphiphile' molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bacter- icidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), inclu- ding S. aureus strains resistant

2004-01-01

160

Drug-positive rates for the Army from fiscal years 1991 to 2000 and for the National Guard from Fiscal years 1997 to 2000.  

PubMed

This article examines the positive rate by drug for all urinalysis specimens tested by the U.S. Army from fiscal year 1991 (FY91) to FY00 and for the Army National Guard (NG) from FY97 to FY00. The average positive rate for the Army from FY91 to FY00 was 0.84%. In FY00, the Army rate reached a 10-year high of 1.04%. From FY97 to FY00, the NG positive rate declined from 3.4% to 2.16% but was significantly (p < 0.05) higher than the Army rate during the same period. Marijuana and cocaine are the most abused drugs for both the Army and NG. The positive rate for marijuana in the Army from FY91 to FY00 was 0.51%, and the cocaine rate was 0.19%. The NG marijuana-positive rate from FY97 to FY00 was 1.70%, and the cocaine rate was 0.51%. The positive rate for all other drugs of abuse tested was less than 0.3% for both the Army and NG during the same periods. The overall positive rate for the Army and NG are below those estimated (6.3%) in the civilian population. PMID:12053845

Bruins, Mark R; Okano, Catherine K; Lyons, Timothy P; Lukey, Brian J

2002-05-01

161

Why does formation of 1,3-dimethylenecyclobutane-2,4-diyl from 1,3-dimethylenecyclobutane show a large positive deviation from bond enthalpy additivity?  

Microsoft Academic Search

B3LYP\\/6-31G? calculations have been performed in order to better understand the reasons for the large positive deviation from bond enthalpy additivity (BEA), found by Hill and Squires, for formation of triplet 1,3-dimethylenecyclobutane-2,4-diyl (2) from 1,3-dimethylenecyclobutane (3). The calculations find that, in contrast to the formation of diradical 2 from diene 3, formation of 2 from 1-methyl-3-methylenecyclobutene (5) has a negative

D. Y Zhang; W. T Borden

2000-01-01

162

Accuracy and Potential Usefulness of Triplex Real-Time PCR for Improving Antibiotic Treatment of Patients with Blood Cultures Showing Clustered Gram-Positive Cocci on Direct Smears?  

PubMed Central

Bacterial identification and antibiotic susceptibility testing currently require 48 h when a first blood culture (BC) is positive for clustered gram-positive cocci on direct smear examination (DSE). Meanwhile, antibiotic treatment is often inadequate, reducing the chances of effective treatment or creating unnecessary selective pressure. A new real-time PCR (RT-PCR) technique that differentiates Staphylococcus aureus from coagulase-negative staphylococci (CoNS) and detects methicillin resistance in 90 min in BC bottles could help solve these problems. BC bottles from 410 patients with gram-positive cocci on DSE were processed by current methods, and patients' treatments were prospectively recorded. The RT-PCR assay was performed on aliquots of these BCs, which had been kept frozen. For the 121 patients who had true bacteremia, we established whether the faster availability of RT-PCR results could have led to the initiation of treatments different from those actually given. RT-PCR sensitivity and specificity were 100% for differentiating between S. aureus and CoNS and detecting methicillin resistance with two manufacturers' BC bottles. For 31/86 (36%) of the S. aureus-infected patients and for 8/35 (23%) of the CoNS-infected patients who either had suboptimal or nonoptimal treatment or were untreated 48 h after positivity was detected, the early availability of RT-PCR results could have allowed more effective treatment. Unnecessary glycopeptide treatments could have been avoided for 28 additional patients. The use of RT-PCR would increase treatment effectiveness in patients with staphylococcal bacteremia and reduce the selective pressure created by glycopeptides. PMID:18417663

Ruimy, Raymond; Dos-Santos, Marie; Raskine, Laurent; Bert, Frédéric; Masson, René; Elbaz, Sandrine; Bonnal, Christine; Lucet, Jean-Christophe; Lefort, Agnès; Fantin, Bruno; Wolff, Michel; Hornstein, Michele; Andremont, Antoine

2008-01-01

163

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

PubMed Central

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

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

2014-01-01

164

Mifepristone (RU486), a pure antiprogesterone drug, in combination with vinblastine for the treatment of progesterone receptor-positive desmoid tumor.  

PubMed

We report the case of a patient who developed a desmoid tumor following total proctocolectomy and J-pouch reconstruction that was unresponsive to any medical treatment. Based on estrogen receptor alpha (ERalpha) and progesterone receptor (PR) evaluation (ERalpha-negative, but PR-positive), treatment with mifepristone, a pure antiprogesterone drug, was initiated, and partial tumor regression was achieved. PMID:20585823

Halevy, A; Samuk, I; Halpern, Z; Copel, L; Sandbank, J; Ziv, Y

2010-09-01

165

Ehrlichia ruminantium Major Antigenic Protein Gene (map1) Variants Are Not Geographically Constrained and Show No Evidence of Having Evolved under Positive Selection Pressure  

PubMed Central

In a search for tools to distinguish antigenic variants of Ehrlichia ruminantium, we sequenced the major antigenic protein genes (map1 genes) of 21 different isolates and found that the sequence polymorphisms were too great to permit the design of probes which could be used as markers for immunogenicity. Phylogenetic comparison of the 21 deduced MAP1 sequences plus another 9 sequences which had been previously published did not reveal any geographic clustering among the isolates. Maximum likelihood analysis of codon and amino acid changes over the phylogeny provided no statistical evidence that the gene is under positive selection pressure, suggesting that it may not be important for the evasion of host immune responses. PMID:11682561

Allsopp, M. T. E. P.; Dorfling, C. M.; Maillard, J. C.; Bensaid, A.; Haydon, D. T.; van Heerden, H.; Allsopp, B. A.

2001-01-01

166

Magic Show  

Microsoft Academic Search

With a concentration in theatre, I created a magic show from scratch. Over the course of the semester, I researched both the effects (more commonly known as magic tricks) in a variety of styles, especially mentalism, along with the patter, or script, that is integral in making a good effect into something utterly amazing. I chose a certain set of

Zachary Brass

2012-01-01

167

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

PubMed

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

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

2015-03-01

168

Single nucleotide polymorphisms of PAD1 and FDC1 show a positive relationship with ferulic acid decarboxylation ability among industrial yeasts used in alcoholic beverage production.  

PubMed

Among industrial yeasts used for alcoholic beverage production, most wine and weizen beer yeasts decarboxylate ferulic acid to 4-vinylguaiacol, which has a smoke-like flavor, whereas sake, shochu, top-fermenting, and bottom-fermenting yeast strains lack this ability. However, the factors underlying this difference among industrial yeasts are not clear. We previously confirmed that both PAD1 (phenylacrylic acid decarboxylase gene, YDR538W) and FDC1 (ferulic acid decarboxylase gene, YDR539W) are essential for the decarboxylation of phenylacrylic acids in Saccharomyces cerevisiae. In the present study, single nucleotide polymorphisms (SNPs) of PAD1 and FDC1 in sake, shochu, wine, weizen, top-fermenting, bottom-fermenting, and laboratory yeast strains were examined to clarify the differences in ferulic acid decarboxylation ability between these types of yeast. For PAD1, a nonsense mutation was observed in the gene sequence of standard top-fermenting yeast. Gene sequence analysis of FDC1 revealed that sake, shochu, and standard top-fermenting yeasts contained a nonsense mutation, whereas a frameshift mutation was identified in the FDC1 gene of bottom-fermenting yeast. No nonsense or frameshift mutations were detected in laboratory, wine, or weizen beer yeast strains. When FDC1 was introduced into sake and shochu yeast strains, the transformants exhibited ferulic acid decarboxylation activity. Our findings indicate that a positive relationship exists between SNPs in PAD1 and FDC1 genes and the ferulic acid decarboxylation ability of industrial yeast strains. PMID:24507903

Mukai, Nobuhiko; Masaki, Kazuo; Fujii, Tsutomu; Iefuji, Haruyuki

2014-07-01

169

Gene expression profile of Xenopus A6 cells cultured under random positioning machine shows downregulation of ion transporter genes and inhibition of dome formation  

NASA Astrophysics Data System (ADS)

Random positioning machine (RPM) devices that generate a simulated microgravity environment of approximately 0 g prevent the formation of dome structures in Xenopus kidney-derived A6 cells. In the present study, the gene expression profile of A6 cells cultured under RPM was determined using the Xenopus 22K scale microarray, and those genes up- or downregulated twofold or more were investigated. We identified 29 genes (up, 25 genes; down, 4 genes) on day 5, 68 genes (up, 25 genes; down, 43 genes) on day 8, 111 genes (up, 69 genes; down, 42 genes) on day 10, and 283 genes (up, 153 genes; down, 130 genes) on day 15 of culture under RPM. These genes were classified according to categories described in the KOG database, such as "extracellular structure", "cytoskeleton", and "transcription". Almost all the genes involved in "inorganic ion transport and metabolism" were downregulated under RPM. Our study further investigated some of these including the epithelial Na + channel (ENaC) and Na +/K +-ATPase transporter genes. A specific inhibitor of Na +/K +-ATPases, ouabain, inhibited dome formation in the A6 cells, even under control culturing conditions of 1 g (the static condition). Together these data suggested that downregulation of sodium ion transporter gene expression plays a significant role in the RPM-dependent prevention of the dome formation in kidney epithelial cells.

Ikuzawa, Masayuki; Akiduki, Saori; Asashima, Makoto

170

Flomoxef showed excellent in vitro activity against clinically important gram-positive and gram-negative pathogens causing community- and hospital-associated infections.  

PubMed

The objective of this study was to better understand the in vitro activity of flomoxef against clinical pathogens. A total of 545 clinical isolates, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus, Streptococcus pneumoniae, and Streptococcus pyogenes, were isolated consecutively from clinical specimens from Peking Union Medical College Hospital in 2013. MICs were determined using broth microdilution method. esbl and ampC genes were detected by polymerase chain reaction and sequencing. Flomoxef showed excellent activity against E. coli, K. pneumoniae, and P. mirabilis isolates, with susceptibility rate of 88.8%, 88.3%, and 97.7%, separately. Moreover, flomoxef exhibited great activity against extended-spectrum beta-lactamase (ESBL) producers, with MIC50/MIC90 of 0.125/(0.5-1) ?g/mL. Flomoxef showed MIC50/MIC90 of 0.5/0.5?g/mL against MSSA, 0.125/0.25?g/mL against S. pyogenes, and 2/16?g/mL against S. pneumoniae. In conclusion, flomoxef is one of the cephamycins showing excellent activity against ESBL-producing or ESBL-nonproducing E. coli, K. pneumoniae, and P. mirabilis and was also potent against MSSA, S. pyogenes, and S. pneumoniae. PMID:25641126

Yang, Qiwen; Zhang, Hui; Cheng, Jingwei; Xu, Zhipeng; Hou, Xin; Xu, Yingchun

2015-04-01

171

Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100.  

PubMed

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

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

2014-06-01

172

mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer  

PubMed Central

Background Recent studies have shown that the regulatory effect of microRNAs can be investigated by examining expression changes of their target genes. Given this, it is useful to define an overall metric of regulatory effect for a specific microRNA and see how this changes across different conditions. Results Here, we define a regulatory effect score (RE-score) to measure the inhibitory effect of a microRNA in a sample, essentially the average difference in expression of its targets versus non-targets. Then we compare the RE-scores of various microRNAs between two breast cancer subtypes: estrogen receptor positive (ER+) and negative (ER-). We applied this approach to five microarray breast cancer datasets and found that the expression of target genes of most microRNAs was more repressed in ER- than ER+; that is, microRNAs appear to have higher RE-scores in ER- breast cancer. These results are robust to the microRNA target prediction method. To interpret these findings, we analyzed the level of microRNA expression in previous studies and found that higher microRNA expression was not always accompanied by higher inhibitory effects. However, several key microRNA processing genes, especially Ago2 and Dicer, were differentially expressed between ER- and ER+ breast cancer, which may explain the different regulatory effects of microRNAs in these two breast cancer subtypes. Conclusions The RE-score is a promising indicator to measure microRNAs' inhibitory effects. Most microRNAs exhibit higher RE-scores in ER- than in ER+ samples, suggesting that they have stronger inhibitory effects in ER- breast cancers. PMID:19723326

Cheng, Chao; Fu, Xuping; Alves, Pedro; Gerstein, Mark

2009-01-01

173

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

SciTech Connect

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

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

2009-05-20

174

Lichenoid drug reaction following influenza vaccination in an HIV-positive patient: a case report and literature review.  

PubMed

Lichenoid drug reactions to vaccinations are rare but well-documented events. The vast majority of these reported reactions have been triggered by Hepatitis B vaccination (HBV). We describe an impressive generalized lichenoid drug reaction following the influenza vaccination. A 46-year-old African-American woman with a history of treated human immunodeficiency virus (HIV) disease developed a diffuse, pruritic rash one day following vaccination against the influenza virus. Physical exam and histopathology were consistent with a lichenoid drug eruption. This is only the fifth reported case of lichenoid drug reaction, and only the second generalized case, following influenza vaccination. The patient's underlying HIV disease, known to be a risk factor for both cutaneous drug reactions and more severe manifestations of lichen planus, likely predisposed her to this generalized hypersensitivity phenomenon. PMID:25007374

de Golian, Emily W; Brennan, Christina B; Davis, Loretta S

2014-07-01

175

Mathematical Modeling of Triphasic Viral Dynamics in Patients with HBeAg-Positive Chronic Hepatitis B Showing Response to 24-Week Clevudine Therapy  

PubMed Central

Background Modeling of short-term viral dynamics of hepatitis B with traditional biphasic model might be insufficient to explain long-term viral dynamics. The aim was to develop a novel method of mathematical modeling to shed light on the dissociation between early and long-term dynamics in previous studies. Methods We investigated the viral decay pattern in 50 patients from the phase III clinical trial of 24-week clevudine therapy, who showed virological response and HBsAg decline. Immune effectors were added as a new compartment in the model equations. We determined some parameter values in the model using the non-linear least square minimization method. Results Median baseline viral load was 8.526 Log10copies/mL, and on-treatment viral load decline was 5.683 Log10copies/mL. The median half-life of free virus was 24.89 hours. The median half-life of infected hepatocytes was 7.39 days. The viral decay patterns were visualized as triphasic curves with decreasing slopes over time: fastest decay in the first phase; slowest in the third phase; the second phase in between. Conclusions In the present study, mathematical modeling of hepatitis B in patients with virological response and HBsAg decline during 24-week antiviral therapy showed triphasic viral dynamics with direct introduction of immune effectors as a new compartment, which was thought to reflect the reduction of clearance rate of infected cells over time. This modeling method seems more appropriate to describe long-term viral dynamics compared to the biphasic model, and needs further validation. PMID:23209728

Kim, Hwi Young; Kwon, Hee-Dae; Jang, Tae Soo; Lim, Jisun; Lee, Hyo-Suk

2012-01-01

176

Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry.  

PubMed

A new-multi residue method was developed for the environmental monitoring of 65 stimulants, opiod and morphine derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors, human urine indicators and their metabolites in wastewater and surface water. The proposed analytical methodology offers rapid analysis for a large number of compounds, with low limits of quantification and utilises only one solid-phase extraction-ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry (SPE-LC-MS/MS) method, thus overcoming the drawbacks of previously published procedures. The method employed solid phase extraction with the usage of Oasis MCX sorbent and subsequent ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry. The usage of a 1.7 ?m particle size column (1 mm×150 mm) resulted in very low flow rates (0.04 mLmin(-1)), and as a consequence gave good sensitivity, low mobile phase consumption and short retention times for all compounds (from 2.9 to 23.1 min). High SPE recoveries (>60%) were obtained for the majority of compounds. The mean correlation coefficients of the calibration curves were typically higher than 0.997 and showed good linearity in the range 0-1000 ?gL(-1). The method limits of detection ranged from 0.1 ngL(-1) for compounds including cocaine, benzoylecgonine, norbenzoylecgonine and 2-oxo-3-hydroxy-LSD to 100 ngL(-1) for caffeine. Method quantification limits ranged from 0.5 to 154.2 ngL(-1). Intra- and inter-day repeatabilities were on average less than 10%. The method accuracy range was within -33.1 to 30.1%. The new multi-residue method was used to analyse drugs of abuse in wastewater and river water in the UK environment. Of the targeted 65 compounds, 46 analytes were detected at levels above the method quantification limit (MQL) in wastewater treatment plant (WWTP) influent, 43 in WWTP effluent and 36 compounds in river water. PMID:21334631

Baker, David R; Kasprzyk-Hordern, Barbara

2011-03-25

177

The Human Endometrium Expresses the Glycoprotein Mucin-1 and Shows Positive Correlation for Thomsen-Friedenreich Epitope Expression and Galectin-1 Binding  

PubMed Central

Mucin 1 (MUC1) is a glycoprotein in human endometrium and is abundant at the luminal epithelial surface in the receptive phase. It has a highly glycosylated ecto-domain that contains keratan sulfate chains, that disappears at the time of implantation. In addition, the glycoforms on MUC1 differ in fertile and infertile women. Therefore the aims of this study were investigations on glycosylation of MUC1 with the Thomsen-Friedenreich (TF) epitope on normal human endometrium throughout the menstrual cycle and binding of galectin-1 on the TF epitope in the endometrium and the expression of galectin-1 on the human oocyte. Human endometrial tissue was obtained from 54 premenopausal patients and was immunohistochemically analyzed with monoclonal antibodies against MUC1, TF epitope, galectin-1, and biotinylated galectin-1. In addition, human oocytes were analyzed for TF, galectin-1 expression, and galectin-1 binding. We identified a significant upregulation of MUC1 and TF epitope and, in addition, galectin-1 binding in glandular epithelium and epithelial apical surface tissue from proliferative to secretory phase. With double staining experiments, we identified a coexpression of TF and MUC1 in the early secretory phase and galectin-1 binding to TF during the same period of time. In addition we identified TF epitope and galectin-1 expression plus binding on the human oocyte and irregularly fertilized oocytes. Upregulation of TF epitope on the glandular epithelium and epithelial apical surface tissue in the secretory phase and binding of galectin-1 at the same time show the possibility of galectin-1–mediated trophectoderm binding to the endometrium within the window of implantation. (J Histochem Cytochem 57:871–881, 2009) PMID:19506091

Jeschke, Udo; Walzel, Hermann; Mylonas, Ioannis; Papadopoulos, Panos; Shabani, Naim; Kuhn, Christina; Schulze, Sandra; Friese, Klaus; Karsten, Uwe; Anz, David; Kupka, Markus S.

2009-01-01

178

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

PubMed

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

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

2015-02-01

179

Novel Aptamer-Nanoparticle Bioconjugates Enhances Delivery of Anticancer Drug to MUC1-Positive Cancer Cells In Vitro  

PubMed Central

MUC1 protein is an attractive target for anticancer drug delivery owing to its overexpression in most adenocarcinomas. In this study, a reported MUC1 protein aptamer is exploited as the targeting agent of a nanoparticle-based drug delivery system. Paclitaxel (PTX) loaded poly (lactic-co-glycolic-acid) (PLGA) nanoparticles were formulated by an emulsion/evaporation method, and MUC1 aptamers (Apt) were conjugated to the particle surface through a DNA spacer. The aptamer conjugated nanoparticles (Apt-NPs) are about 225.3 nm in size with a stable in vitro drug release profile. Using MCF-7 breast cancer cell as a MUC1-overexpressing model, the MUC1 aptamer increased the uptake of nanoparticles into the target cells as measured by flow cytometry. Moreover, the PTX loaded Apt-NPs enhanced in vitro drug delivery and cytotoxicity to MUC1+ cancer cells, as compared with non-targeted nanoparticles that lack the MUC1 aptamer (P<0.01). The behavior of this novel aptamer-nanoparticle bioconjugates suggests that MUC1 aptamers may have application potential in targeted drug delivery towards MUC1-overexpressing tumors. PMID:21912664

Duan, Jinhong; Yuan, Wei; Wang, Chen; Xu, Haiyan; Yang, Xian-Da

2011-01-01

180

Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy.  

PubMed

We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (D-phenylalanine) and neurotransmitter precursors (L-amino- acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates found increases in the dopamine D2 receptors (DRD2) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens, significantly reduced both ethanol preference (43%) and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This work further suggests that high levels of DRD2 may be protective against alcohol abuse [JAMA 263 (1990) 2055; Arch, Gen. Psychiatr. 48 (1991) 648]. The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies. In addition, other dopaminergic receptor gene polymorphisms have also associated with opioid dependence. For example, Kotler et al. [Mol. Phychiatr. 3 (1997) 251] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46. This has been confirmed by Li et al. [Mol. Psychiatry 2 (1997) 413] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts. Similarly Duaux et al. [Mol. Psychiatry 3 (1998) 333] in French Heroin addicts, found a significant association with homozygotes alleles of the DRD3-Bal 1. A study from NIAAA, provided evidence which strongly suggests that DRD2 is a susceptibility gene for substance abusers across multiple populations (2003). Moreover, there are a number of studies utilizing amino-acid and enkephalinase inhibition therapy showing reduction of alcohol, opiate, cocaine and sugar craving behavior in human trials (see Table 1). Over the last decade, a new rapid method to detoxify either methadone or heroin addicts utilizing Trexan sparked interest in many treatment centers throughout the United States, Canada, as well as many countries on a worldwide basis. In using the combination of Trexan and amino-acids, results were dramatic in terms of significantly enhancing compliance to continue taking Trexan. The average number of days of compliance calculated on 1000 patients, without amino-acid therapy, using this rapid detoxification method is only 37 days. In contrast, the 12 subjects tested, receiving both the Trexan and amino-acid therapy was relapse-free or reported taking the combination for an average of 262 days (p < 0.0001F). Thus coupling amino-acid therapy and enkephalinase inhibition while blocking the delta-receptors with a pure narcotic antagonist may be quite promising as a novel method to induce rapid detox in chronic methadone patients. This may also have important ramifications in the treatment of both opiate and alcohol-dependent individuals, especially as a relapse prevention tool. It may also be interesting too further test this hypothesis with the sublingual combination of the partial opiate mu receptor agonist buprenorphrine. PMID:15288384

Chen, Thomas J H; Blum, Kenneth; Payte, James T; Schoolfield, John; Hopper, David; Stanford, Mathew; Braverman, Eric R

2004-01-01

181

Unprotected sex among HIV-positive injection drug-using women and their serodiscordant male partners: role of personal and partnership influences.  

PubMed

We investigated the characteristics of human immunodeficiency virus (HIV)-positive injection drug-using women who reported unprotected vaginal and/or anal sex with HIV-negative or unknown serostatus (serodiscordant) male partners. Of 426 female study participants, 370 were sexually active. Of these women, 39% (144/370) and 40% (148/370) reported vaginal and/or anal sex with serodiscordant main and casual partners, respectively. Sixty percent of women inconsistently used condoms with their serodiscordant main partners, whereas 53% did so with casual partners. In multivariate analysis, during sex with main partners, inconsistent condom users were less likely to feel confident about achieving safe sex (self-efficacy), personal responsibility for limiting HIV transmission, and that their partner supported safe sex. Inconsistent condom use was also more likely among women who held negative beliefs about condoms and in couplings without mutual disclosure of HIV status. Regarding sex with casual partners, inconsistent condom users were more likely to experience psychologic distress, engage in sex trading, but they were less likely to feel confident about achieving safe sex. These findings suggest that there are widespread opportunities for the sexual transmission of HIV from drug-using women to HIV-uninfected men, and that reasons vary by type of partnership. Multifaceted interventions that address personal, dyadic, and addiction problems are needed for HIV-positive injection drug-using women. PMID:16760799

Latka, Mary H; Metsch, Lisa R; Mizuno, Yulo; Tobin, Karin; Mackenzie, Sonia; Arnsten, Julia H; Gourevitch, Marc N

2006-06-01

182

Prediction of Positions of Active Compounds Makes It Possible To Increase Activity in Fragment-Based Drug Development  

PubMed Central

We have developed a computational method that predicts the positions of active compounds, making it possible to increase activity as a fragment evolution strategy. We refer to the positions of these compounds as the active position. When an active fragment compound is found, the following lead generation process is performed, primarily to increase activity. In the current method, to predict the location of the active position, hydrogen atoms are replaced by small side chains, generating virtual compounds. These virtual compounds are docked to a target protein, and the docking scores (affinities) are examined. The hydrogen atom that gives the virtual compound with good affinity should correspond to the active position and it should be replaced to generate a lead compound. This method was found to work well, with the prediction of the active position being 2 times more efficient than random synthesis. In the current study, 15 examples of lead generation were examined. The probability of finding active positions among all hydrogen atoms was 26%, and the current method accurately predicted 60% of the active positions.

Fukunishi, Yoshifumi

2011-01-01

183

Keeping Show Pigs Healthy  

E-print Network

within a well-managed farm ? Vaccinating to prevent serious diseases ? Deworming the pigs routinely ? Having sick pigs promptly diagnosed and treated ? Using prescribed drugs properly Starting with healthy PigS To prevent disease outbreaks in show... of disease problems. Antibiotics are totally ineffective in preventing common viral diseases such as transmissible gas- troenteritis and swine influenza. Also, vaccines are not available for all swine diseases and must be giv- en long before the pigs...

Lawhorn, D. Bruce

2006-10-13

184

Relationship of consumers' perceptions of drugs to drug use.  

PubMed Central

To examine consumers' perceptions of nonprescription and prescription drugs and the relationship of these perceptions to drug use, a sample of 200 adult residents of a northern midwestern area who were similar in age and education to the national population was surveyed. Respondents who rated nonprescription drugs as safe and somewhat effective used nearly 90 percent less nonprescription drugs than respondents rating these drugs as safe and ineffective. Respondents who rated prescription drugs as unsafe used approximately 60 percent less of them than respondents rating them as somewhat safe or safe. Data for the study were collected from March 15 to May 15, 1978. The respondents' perceptions of nonprescription and prescription drugs in respect to safety, efficacy, side effects, and overdose effects were measured on a thermometer scale, with anchors at three points (100 degrees for the most positive perception, 50 degrees for the midpoint, and 0 degrees for the most negative perception). Drug use, based on the respondents' recollections, was measured for 2 days before the interview. The respondents rated prescription drugs as safer and more effective than nonprescription drugs, but as having more dangerous overdose effects. Two-way analysis of variance showed that perceptions of the safety and effectiveness of nonprescription drugs and the interaction between these two variables were related to the use of these drugs. Perceptions of the safety of prescription drugs were related to their use. PMID:6828642

Grahn, J L

1983-01-01

185

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

PubMed

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

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

2013-12-01

186

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis: the case of Prozac and the fluoxetine generics.  

PubMed

Samples of fluoxetine of different origin were submitted to natural abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting. PMID:17920397

Brenna, Elisabetta; Fronza, Giovanni; Fuganti, Claudio

2007-10-10

187

Irinotecan Plus S-1 Followed by Hepatectomy for a Patient with Initially Unresectable Colorectal Liver Metastases, Who Showed Severe Drug Rash with Oxaliplatin Plus 5-FU and Leucovorin (FOLFOX)  

PubMed Central

For unresectable colorectal liver metastases (CRLM), hepatic resection with or without chemotherapy is the only curative treatment that sufficiently achieves long-term survival. However, occasional severe allergic responses to anticancer drugs necessitate treatment discontinuation. A 45-year-old woman presented with metachronous unresectable colorectal liver metastases. Chemotherapy with oxaliplatin plus 5-FU and leucovorin (FOLFOX) was initiated, but severe allergic dermatitis developed after the second cycle. Although she reported no prior history of adverse reactions to tegafur-uracil, a drug lymphocyte stimulation test showed an allergic response to 5-FU. We subsequently replaced with Irinotecan plus S-1 (IRIS) chemotherapy which was well tolerated and resulted in a partial response after 3 cycles. As a result, right trisectionectomy was successfully performed and no recurrence was detected in the following 3 years. A severe allergic reaction to intravenous 5-FU-containing drug regimens can be successfully alleviated by switching to S-1-containing regimens such as IRIS or S-1 plus oxaliplatin (SOX). PMID:25031875

Komori, Hiroyuki; Beppu, Toru; Sakamoto, Yasuo; Miyamoto, Yuji; Hayashi, Hiromitsu; Imai, Katsunori; Nitta, Hidetoshi; Watanabe, Masayuki; Baba, Hideo

2014-01-01

188

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

PubMed Central

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

2011-01-01

189

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

Microsoft Academic Search

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

Joseph T Hanlon; Catherine I Lindblad; Shelly L Gray

2004-01-01

190

PPARalpha agonists positively and negatively regulate the expression of several nutrient/drug transporters in mouse small intestine.  

PubMed

A systematic analysis to examine the effects of peroxisome proliferator-activated receptor (PPAR)alpha agonists on the expression levels of all the nutrient/drug plasma-membrane transporters in the mouse small intestine was performed. Transporter mRNAs that were induced or repressed by two independent PPARalpha-specific agonists were identified by a genome-wide microarray method, and the changes were confirmed by real-time PCR using RNA isolated from the intestines and livers of wild-type and PPARalpha-null mice. Expression levels of seven nutrient/drug transporters (Abcd3, Octn2/Slc22a5, FATP2/Slc27a2, Slc22a21, Mct13/Slc16a13, Slc23a1 and Bcrp/Abcg2) in the intestine were up-regulated and the expression level of one (Mrp1/Abcc1) was down-regulated by PPARalpha; although the previously report that the H(+)/peptide co-transporter 1 (Pept1) is up-regulated by PPARalpha was not replicated in our study. We propose that the transport processes can be coordinately regulated with intracellular metabolism by nutrient nuclear receptors. PMID:17978498

Hirai, Toshitake; Fukui, Yuka; Motojima, Kiyoto

2007-11-01

191

The impact of a brief motivational intervention on unprotected sex and sex while high among drug-positive emergency department patients who receive STI/HIV VC/T and drug treatment referral as standard of care.  

PubMed

This randomized, controlled trial, conducted among out-of-treatment heroin/cocaine users at an emergency department visit, tests the impact on sexual risk of adding brief motivational intervention (B-MI) to point-of-service testing, counseling and drug treatment referral. 1,030 enrollees aged 18-54 received either voluntary counseling/testing (VC/T) with drug treatment referral, or VC/T, referral, and B-MI, delivered by an outreach worker. We measured number and proportion of non-protected sex acts (last 30 days) at 6 and 12 months (n = 802). At baseline, 70% of past-30-days sex acts were non-protected; 35% of sex acts occurred while high; 64% of sexual acts involved main, 24% casual and 12% transactional sex partners; 1.7% tested positive for an STI, and 8.8% for HIV. At six or 12 month follow-up, 20 enrollees tested positive for Chlamydia and/or Gonorrhea, and 6 enrollees HIV sero-converted. Self-reported high-risk behaviors declined in both groups with no significant between-group differences in behaviors or STI/HIV incidence. PMID:22261830

Bernstein, Edward; Ashong, Desiree; Heeren, Timothy; Winter, Michael; Bliss, Caleb; Madico, Guillermo; Bernstein, Judith

2012-07-01

192

Association between heroin use, needle sharing and tattoos received in prison with hepatitis B and C positivity among street-recruited injecting drug users in New Mexico, USA.  

PubMed Central

This study aimed to assess the seroprevalence and risk factors for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV-1 infections among injecting drug users (IDU) in New Mexico. Serological and behavioural surveys were conducted in conjunction with street-based outreach, education and HIV counselling and testing. High rates of antibody positivity for HCV (82.2%) and HBV (61.1%), and a low rate for HIV (0.5%) were found. In multivariate analyses, both HBV and HCV infection were positively associated with increasing age, increasing years of injection and heroin use. Receipt of a tattoo in prison/jail was associated with HBV (odds ratio = 2.3, 95% confidence interval 1.4, 3.8) and HCV (OR = 3.4, 95% CI = 1.6, 7.5) infections. Prevention of bloodborne pathogens among IDUs should focus on young users, early in their drug use experience. Studies examining the relationship between tattooing and HBV and HCV infection are needed as are efforts to promote sterile tattooing, in prisons and elsewhere. PMID:11811881

Samuel, M. C.; Doherty, P. M.; Bulterys, M.; Jenison, S. A.

2001-01-01

193

Psychosocial predictors of current drug use, drug problems, and physical drug dependence in homeless women  

Microsoft Academic Search

We examined risk and protective factors associated with three qualitatively different drug use constructs describing a continuum of drug use among a sample of 1,179 homeless women. Relationships among positive and negative sources of social support, positive and negative coping strategies, depression, and the drug constructs of current drug use, drug problems, and physical drug dependence were assessed using structural

Elisha R Galaif; Adeline M Nyamathi; Judith A Stein

1999-01-01

194

Discriminative Stimulus Effects of the GABAB Receptor-Positive Modulator rac-BHFF: Comparison with GABAB Receptor Agonists and Drugs of Abuse  

PubMed Central

GABAB receptor-positive modulators are thought to have advantages as potential medications for anxiety, depression, and drug addiction. They may have fewer side effects than GABAB receptor agonists, because selective enhancement of activated receptors could have effects different from nonselective activation of all receptors. To examine this, pigeons were trained to discriminate the GABAB receptor-positive modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) from its vehicle. The discriminative stimulus effects of rac-BHFF were not mimicked by the GABAB receptor agonists baclofen and ?-hydroxybutyrate (GHB), not by diazepam, and not by alcohol, cocaine, and nicotine, whose self-administration has been reported to be attenuated by GABAB receptor-positive modulators. The discriminative stimulus effects of rac-BHFF were not antagonized by the GABAB receptor antagonist 3-aminopropyl (diethoxymethyl)phosphinic acid (CGP35348) but were attenuated by the less efficacious GABAB receptor-positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol (CGP7930), suggesting the possibility that rac-BHFF produces its discriminative stimulus effects by directly activating GABAB2 subunits of GABAB receptors. At a dose 10-fold lower than the training dose, rac-BHFF enhanced the discriminative stimulus effects of baclofen, but not of GHB. This study provides evidence that the effects of GABAB receptor-positive modulators are not identical to those of GABAB receptor agonists. In addition, the results suggest that positive modulation of GABAB receptors does not produce discriminative stimulus effects similar to those of benzodiazepines, alcohol, cocaine, and nicotine. Finally, the finding that rac-BHFF enhanced effects of baclofen but not of GHB is consistent with converging evidence that the populations of GABAB receptors mediating the effects of baclofen and GHB are not identical. PMID:23275067

Cheng, Kejun; Rice, Kenner C.

2013-01-01

195

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort  

PubMed Central

BACKGROUND: Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM). OBJECTIVE: To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use. METHODS: Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ?2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY). RESULTS: In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load. CONCLUSIONS: These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV. PMID:25798149

Burchell, Ann N; Gardner, Sandra L; Mazzulli, Tony; Manno, Michael; Raboud, Janet; Allen, Vanessa G; Bayoumi, Ahmed M; Kaul, Rupert; McGee, Frank; Millson, Peggy; Remis, Robert S; Wobeser, Wendy; Cooper, Curtis; Rourke, Sean B

2015-01-01

196

drug discovery drug discovery  

E-print Network

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

197

Discriminative stimulus effects of the GABAB receptor-positive modulator rac-BHFF: comparison with GABAB receptor agonists and drugs of abuse.  

PubMed

GABA(B) receptor-positive modulators are thought to have advantages as potential medications for anxiety, depression, and drug addiction. They may have fewer side effects than GABA(B) receptor agonists, because selective enhancement of activated receptors could have effects different from nonselective activation of all receptors. To examine this, pigeons were trained to discriminate the GABA(B) receptor-positive modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) from its vehicle. The discriminative stimulus effects of rac-BHFF were not mimicked by the GABA(B) receptor agonists baclofen and ?-hydroxybutyrate (GHB), not by diazepam, and not by alcohol, cocaine, and nicotine, whose self-administration has been reported to be attenuated by GABA(B) receptor-positive modulators. The discriminative stimulus effects of rac-BHFF were not antagonized by the GABA(B) receptor antagonist 3-aminopropyl (diethoxymethyl)phosphinic acid (CGP35348) but were attenuated by the less efficacious GABA(B) receptor-positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol (CGP7930), suggesting the possibility that rac-BHFF produces its discriminative stimulus effects by directly activating GABA(B2) subunits of GABA(B) receptors. At a dose 10-fold lower than the training dose, rac-BHFF enhanced the discriminative stimulus effects of baclofen, but not of GHB. This study provides evidence that the effects of GABA(B) receptor-positive modulators are not identical to those of GABA(B) receptor agonists. In addition, the results suggest that positive modulation of GABA(B) receptors does not produce discriminative stimulus effects similar to those of benzodiazepines, alcohol, cocaine, and nicotine. Finally, the finding that rac-BHFF enhanced effects of baclofen but not of GHB is consistent with converging evidence that the populations of GABA(B) receptors mediating the effects of baclofen and GHB are not identical. PMID:23275067

Koek, Wouter; Cheng, Kejun; Rice, Kenner C

2013-03-01

198

Addressing social barriers and closing the gender knowledge gap: exposure to road shows is associated with more knowledge and more positive beliefs, attitudes and social norms regarding exclusive breastfeeding in rural Zimbabwe.  

PubMed

Exclusive breastfeeding (EBF) is rarely practiced despite its significant child survival benefits. A key constraint to increasing EBF rates in Zimbabwe and most of the developing world is that key decision makers (fathers/partners and other family members) are often poorly informed about EBF and do not attend antenatal clinics where health information is routinely provided. Informed by formative research, a district-wide campaign was conducted in rural Zimbabwe to encourage EBF and expressing and heat treating (EHT) breast milk as a means to maintain EBF. The campaign combined traditional strategies of education, counselling and outreach through health service delivery with a novel road show 'edutainment' intervention to reach men and other community members. A post campaign evaluation measured the association of road show exposure with 20 knowledge items and summative scores of social norms, beliefs and attitudes obtained through exploratory factor analysis. In adjusted models, road show exposure was associated with correct EBF knowledge (?=1.0, 0.001), EHT knowledge (?=1.3, P<0.001) and greater perceived benefits of condom use during pregnancy and breastfeeding (?=0.5, P<0.001), and more positive EBF social norms (?=0.6, P<0.001), EBF beliefs and attitudes (?=1.0, P<0.001) and attitudes towards condom use during breastfeeding (?=0.6, P<0.001). Road show exposure was more strongly associated with EBF knowledge among men (P-value for gender×exposure group interaction=0.03), suggesting that it also closed the knowledge gap between men and women. Longitudinal studies will determine whether road shows were associated with changes in EBF practices. PMID:21972843

Jenkins, Alison L; Tavengwa, Naume V; Chasekwa, Bernard; Chatora, Kumbirai; Taruberekera, Noah; Mushayi, Wellington; Madzima, Rufaro C; Mbuya, Mduduzi N N

2012-10-01

199

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

PubMed Central

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

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

2015-01-01

200

Prevalence of Sexually Acquired Antiretroviral Drug Resistance in a Community Sample of HIV-Positive Men Who Have Sex with Men in New York City  

PubMed Central

Abstract To examine antiretroviral (ARV) drug resistance, we recruited a community sample (n=347) of sexually active HIV-positive men who have sex with men (MSM) in New York City, each of whom completed a structured interview and donated a blood sample for HIV genotyping. Participants reported high levels of sexual activity, with 94.6% reporting at least one sexual contact in the past month, and an average of 3.13 partners during this time. Anal intercourse was common, with 70.7% reporting at least one act of insertive anal intercourse (21% of whom reported ejaculating inside their partner without a condom) and 62.1% reporting at least one act of receptive anal intercourse during this time (22.6% of whom received ejaculate without a condom). Seventeen percent reported having sex with a woman in the past year. Although 17.4% of participants reported having ever injected drugs, no association was found between injection and antiretroviral resistance. Average HIV diagnosis was 12.1 years prior to the interview, and 92.1% had taken ARV medication. Sexually transmitted infections (STIs) were widely reported, with 78% having been diagnosed with an STI since being diagnosed with HIV. A genotype was obtained for 188 (54.7%) of the samples and 44.7% revealed mutations conferring resistance to at least one ARV. Resistance to at least one ARV within a given class of medication was most common for nucleoside reverse transcriptase inhibitors (30.3%) and non-nucleoside reverse transcriptase inhibitors (27.7%) and least common for protease inhibitors (18.1%). The combination of high prevalence of antiretroviral resistance and risky sexual practices makes transmission between sex partners a likely mode of acquisition. PMID:21457055

Clatts, Michael C.; Parker, Monica M.; Colon, Vivian; Hallack, Renee; Messina, Maria G.

2011-01-01

201

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

PubMed Central

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

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

2011-01-01

202

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

PubMed

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

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

2011-12-01

203

Consumer choice of purchasing private-label drugs: an empirical study in China.  

PubMed

This research investigates factors influencing Chinese consumers' purchase choice of private-label drugs over rational brand equivalents. Survey data were collected from 251 Chinese consumers. Results show that their purchase choice of private-label drugs is significantly influenced by drug trust and perceptions of drug quality, but is not influenced by private-label drugs' price advantage. Store trust and perceived drug quality are significant predictors of drug trust. Store trust also positively affects perceived drug quality. Finally, store trust is significantly influenced by product quality and service quality. PMID:24308413

Zhou, Zhiliang; Xue, Yajiong; Ping, Qineng

2013-01-01

204

Prevalence of drug resistance and culture-positive rate among microorganisms isolated from patients with ocular infections over a 4-year period  

PubMed Central

Purpose To investigate the microbial isolates from patients with ocular infections and the trend in the emergence of levofloxacin-resistant strains over the past four years from 2006 to 2009 retrospectively. Patients and methods The subjects were 242 patients with ocular infections or traumas treated in our hospital including outpatients, inpatients, and emergency room patients. Most of them needed urgent care presenting with eye complaints, traumas, or decreased vision. Clinical samples were obtained from discharges, corneal, conjunctival tissues or vitreous fluid or aqueous humor, and cultured. Items for assessment included the patient’s age, the diagnosis, the prevalence of isolated bacteria, and the results of susceptibility tests for levofloxacin (LVFX) cefamezin (CEZ), gentamicin (GM) and vancomycin. This information was obtained from the patients’ medical records. Results There were 156 male patients and 86 female patients who were aged from 2 months old to 94 years old and mean age was 56.8 ± 24.2 years. Of the 242 patients, 78 (32.2%) had positive cultures. The culture-positive rate was significantly higher in male patients than female in total (P = 0.002) and in patients with corneal perforation (P = 0.005). Corneal perforation was the highest culture-positive rate (60.0%), followed by orbital cellulitis (56.5%), blepharitis (50.0%), dacryoadenitis (45.5%), conjunctivitis (38.2%), infectious corneal ulcer (28.5%) and endophthalmitis (24.7%). LVFX-resistant strains accounted for 40 out of a total of 122 strains (32.8%), and the minimum inhibitory concentration (MIC) was significantly higher in LVFX and GM compared with the other antibiotics. There were no vancomycin-resistant strains. Conclusion Attention should be paid to a possible future increase of strains with resistance to LVFX, as commonly prescribed ocular antibiotics bring emergence of resistant bacteria. Although no vancomycin-resistant strains were isolated this drug should be reserved as the last resort, in order to prevent the emergence of vancomycin resistance. PMID:23589677

Shimizu, Yusuke; Toshida, Hiroshi; Honda, Rio; Matsui, Asaki; Ohta, Toshihiko; Asada, Yousuke; Murakami, Akira

2013-01-01

205

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

PubMed Central

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

2013-01-01

206

Nuclear Mapping of Nano-Drug Delivery Systems in Dynamic Cellular Environments  

PubMed Central

Nanoformulations have shown great promise for delivering chemotherapeutics and hold tremendous clinical relevance. However nuclear mapping of the chemo drugs is important to predict the success of the nanoformulation. Herein in this study fluorescence microscopy and a subcellular tracking algorithm were used to map the diffusion of chemotherapeutic drugs in cancer cells. Positively charged nanoparticles efficiently carried the chemo drug across the cell membrane. The algorithm helped map free drug and drug loaded nanoparticles, revealing varying nuclear diffusion pattern of the chemotherapeutics in drug-sensitive and resistant cells in a live dynamic cellular environment. While the drug-sensitive cells showed an exponential uptake of the drug with time, resistant cells showed random and asymmetric drug distribution. Moreover nanoparticles carrying the drug remained in the perinuclear region while the drug got accumulated in the cell nuclei. The tracking approach has enabled us to predict the therapeutic success of different nanoscale formulations of doxorubicin. PMID:22540867

Bhirde, Ashwinkumar A.; Kapoor, Ankur; Liu, Gang; Iglesias-Bartolome, Ramiro; Jin, Albert; Zhang, Guofeng; Xing, Ruijun; Lee, Seulki; Leapman, Richard D.; Gutkind, J Silvio; Chen, Xiaoyuan

2012-01-01

207

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

PubMed Central

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

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

2013-01-01

208

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

PubMed Central

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

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

2014-01-01

209

Workplace drug testing in Italy - critical considerations.  

PubMed

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. PMID:23355251

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

2013-04-01

210

Positive and negative electrospray LC-MS-MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk.  

PubMed

Avermectin endectocides are used for the treatment of cattle against a variety of nematode and arthropod parasites, and consequently may appear in milk after normal or off-label use. The compounds abamectin, doramectin, and ivermectin, contain only C, H and O and may be expected to be detected by LC-MS in negative ion mode. The others contain nitrogen in addition and would be expected to be preferentially ionized in positive mode. The use of positive ion and negative ion methods with electrospray LC-MS-MS were compared. Using negative ion the compounds abamectin, doramectin, ivermectin, emamectin, eprinomectin, and moxidectin gave a curvilinear response and were quantified in raw milk by LC-MS-MS with a triethylamine-acetonitrile buffer over the concentration range 1-60 ppb (microg/kg) using selamectin as the internal standard. The limits of detection (LOD) were between 0.19 ppb (doramectin) and 0.38 ppb (emamectin). The compounds gave maximum sensitivity with positive ionisation from a formic acid-ammonium formate-acetonitrile buffer and were detected in milk (LC-MS-MS) also with a curvilinear response over the range 0.5-60 ppb. Although the positive ion signals were larger, with somewhat lower limits of detection (LOD between 0.06 ppb (doramectin) and 0.32 ppb (moxidectin) the negative ion procedure gave a more linear response and more consistent results. Comparison of spiked samples in the range 2-50 ppb showed a high degree of correlation between the two methods. PMID:17129769

Durden, David A

2007-05-01

211

Drug interactions with antiviral drugs.  

PubMed

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

Taburet, A M; Singlas, E

1996-05-01

212

Synthesis and characterization of lipid immuno-nanocapsules for directed drug delivery: selective antitumor activity against HER2 positive breast-cancer cells.  

PubMed

Lipid nanocapsules (LNC) are usually developed as nanocarriers for lipophilic drug delivery. The surface characteristics of these colloidal particles are determinant for a controlled and directed delivery to target tissues with specific markers. We report the development of immuno-nanocapsules, in which some antibody molecules with different immuno-specificity are conjugated to the nanocapsule surface, offering the standardization of a simple method to obtain vectorized nanosystems with specific recognition properties. Nanocapsules were prepared by a solvent-displacement technique, producing an oily core coated by a functional shell of different biocompatible molecules and surface carboxylic groups. Three different antibodies (one a specific HER2 oncoprotein antibody) were conjugated with these nanoparticles by the carbodiimide method, which allows the covalent immobilization of protein molecules through carboxylic surface groups. The immuno-nanocapsules were completely characterized physico-chemically via electrokinetic and colloidal stability experiments, confirming the correct immobilization of these antibody molecules on the colloidal nanoparticles. Also, additional immunological analyses verified that these IgG-LNC complexes showed the expected specific immuno-response. Finally, different healthy and tumoral breast-cell lines were cultured in vitro with Nile-Red-loaded and docetaxel-loaded HER2 immuno-nanocapsules. The results indicate that our immuno-nanocapsules can increase their uptake in HER2 overexpressing tumoral cell lines. PMID:24134122

Sánchez-Moreno, Paola; Ortega-Vinuesa, Juan Luis; Boulaiz, Houría; Marchal, Juan Antonio; Peula-García, José Manuel

2013-12-01

213

MSM and drug use: A latent class analysis of drug use and related sexual risk behaviors.  

PubMed

This study examined patterns of drug use among gay men and other men who have sex with men (MSM) to identify sub-categories of men whose drug use and sexual behavior place them at especially high risk for HIV. A latent class analysis of a sample of MSM yielded a four-class model with two distinct high drug use sub-groups: one whose drug use concentrated on "sex-drugs" (SDU); and a distinct polydrug use class that showed higher probabilities of using all other drugs assessed. Comparative follow-up analyses indicated the SDU group was also more likely to engage in particular potentially high-risk sexual behaviors, be older, and to be HIV positive. Implications of distinguishing between patterns of drug use for HIV-risk prevention efforts with MSM are discussed. PMID:24065437

McCarty-Caplan, David; Jantz, Ian; Swartz, James

2014-07-01

214

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.  

PubMed

Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programmes. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1-infected drug users receiving antiretroviral therapy (ART) for at least six months in Hanoi, Vietnam. The mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA <1000 copies/mL). Correlates of viral suppression include self-reported > or = 95% adherence (P < 0.01) and current use of trimethoprim/sulphamethoxazole (P < 0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (P = 0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlight the need for adherence promotion, risk reduction programmes, and population-based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

Jordan, M R; La, H; Nguyen, H D; Sheehan, H; Lien, T T M; Duong, D V; Hellinger, J; Wanke, C; Tang, A M

2009-06-01

215

[Drug abuse among new draftees].  

PubMed

The aim of the study was to investigate the pattern of the use of drugs among young conscripts by a test screening of their urine. The participants in the investigation also filled in a questionnaire about use of drugs. The urine samples from 916 young recruits were examined for cannabinoids and 429 were also examined for amphetamines, cocaine, opiates and benzodiazepines. We found 68 (7.8%) positive tests for cannabis and a negligible number of positive tests for other drugs. The questionnaire showed a lower statement of use of drugs though 3.3% stated a daily or weekly use of cannabis. Fifty-eight percent of the soldiers admitted that they had tried cannabis. Six percent had used other drugs. The consumption of alcohol is low during weekdays. We concluded that the conscripts did not constitute a population of drug abusers. We recommend that urine test screening (regular or spot test) should be incorporated in the future medical examination in the Danish Army to pinpoint personnel with a moderate use of cannabis. PMID:8644406

Jørgensen, H O; Calov, E

1996-03-18

216

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

PubMed Central

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

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

2014-01-01

217

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

Microsoft Academic Search

HIV-negative, inner-city adolescents with HIV-infected parents are considered to be at high risk for acquiring HIV themselves.\\u000a Using a modified theory of health behavior, this study examined the effects of maternal HIV infection and psychosocial variables\\u000a on the onset of sexual and drug risk behavior in 144 HIV-negative adolescents with and without HIV-positive mothers. Adolescents\\u000a and their mothers were interviewed

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

2007-01-01

218

LGR5-positive colon cancer stem cells interconvert with drug-resistant LGR5-negative cells and are capable of tumor reconstitution.  

PubMed

The cancer stem cell (CSC) concept has been proposed as an attractive theory to explain cancer development, and CSCs themselves have been considered as targets for the development of diagnostics and therapeutics. However, many unanswered questions concerning the existence of slow cycling/quiescent, drug-resistant CSCs remain. Here we report the establishment of colon cancer CSC lines, interconversion of the CSCs between a proliferating and a drug-resistant state, and reconstitution of tumor hierarchy from the CSCs. Stable cell lines having CSC properties were established from human colon cancer after serial passages in NOD/Shi-scid, IL-2R?(null) (NOG) mice and subsequent adherent cell culture of these tumors. By generating specific antibodies against LGR5, we demonstrated that these cells expressed LGR5 and underwent self-renewal using symmetrical divisions. Upon exposure to irinotecan, the LGR5(+) cells transitioned into an LGR5(-) drug-resistant state. The LGR5(-) cells converted to an LGR5(+) state in the absence of the drug. DNA microarray analysis and immunohistochemistry demonstrated that HLA-DMA was specifically expressed in drug-resistant LGR5(-) cells, and epiregulin was expressed in both LGR5(+) and drug-resistant LGR5(-) cells. Both cells sustained tumor initiating activity in NOG mice, giving rise to a tumor tissue hierarchy. In addition, anti-epiregulin antibody was found to be efficacious in a metastatic model. Both LGR5(+) and LGR5(-) cells were detected in the tumor tissues of colon cancer patients. The results provide new biological insights into drug resistance of CSCs and new therapeutic options for cancer treatment. PMID:23081779

Kobayashi, Shinta; Yamada-Okabe, Hisafumi; Suzuki, Masami; Natori, Osamu; Kato, Atsuhiko; Matsubara, Koichi; Jau Chen, Yu; Yamazaki, Masaki; Funahashi, Shinichi; Yoshida, Kenji; Hashimoto, Eri; Watanabe, Yoshinori; Mutoh, Hironori; Ashihara, Motooki; Kato, Chie; Watanabe, Takeshi; Yoshikubo, Takashi; Tamaoki, Norikazu; Ochiya, Takahiro; Kuroda, Masahiko; Levine, Arnold J; Yamazaki, Tatsumi

2012-12-01

219

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

Microsoft Academic Search

Draft guidelines for the use of oral fluid for workplace drug testing are under development by the Substance Abuse and Mental Health Services Administration (SAMHSA) in cooperation with industry and researchers. Comparison studies of the effectiveness of oral fluid testing versus urine testing are needed to establish scientifically reliable cutoff concentrations for oral fluid testing. We present the results of

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

220

Stretched View Showing 'Victoria'  

NASA Technical Reports Server (NTRS)

[figure removed for brevity, see original site] Stretched View Showing 'Victoria'

This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled in bright green. Finally, the light purple lines and arrow highlight a small crater.

2006-01-01

221

Positive Proof.  

ERIC Educational Resources Information Center

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

Auty, Geoffrey

1988-01-01

222

A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.  

PubMed

The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use. PMID:24702687

Giorda, C B; Nada, E; Tartaglino, B; Marafetti, L; Gnavi, R

2014-11-01

223

Attitudes towards drug legalization among drug users.  

PubMed

Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin. PMID:11853137

Trevino, Roberto A; Richard, Alan J

2002-01-01

224

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

Microsoft Academic Search

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

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

2008-01-01

225

Drug Usage and Attitude Toward Drugs Among College Students  

ERIC Educational Resources Information Center

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

Cross, Herbert J.; Keir, Richard G.

1971-01-01

226

Drug level monitoring in a double-blind multicenter trial: false-positive zidovudine measurements in AIDS clinical trials group protocol 019.  

PubMed Central

Twenty-three different laboratories using four different assay methods reported zidovudine (ZDV; azidothymidine) measurements in a double-blind trial of ZDV for asymptomatic human immunodeficiency virus-infected patients (AIDS Clinical Trials Group Protocol 019). The risk of false-positive ZDV measurements was defined with coded specimens containing no ZDV in a quality control testing program. This testing identified six problem laboratories which reported ZDV levels of greater than or equal to 100 ng/ml for specimens with no ZDV; all of these laboratories used high-performance liquid chromatography. These six laboratories reported a disproportionately high fraction of positive assays for subjects randomized to the placebo group (31% for these 6 laboratories versus 4% for the other 17 laboratories; P less than 0.0001). The high number of false-positive ZDV results reported by these six laboratories suggested that many of the positive results that they reported for patient specimens were also false-positive results. This hypothesis was examined by retesting specimens from patients in the placebo group that had been reported as positive by these laboratories. Ninety percent (19 of 21) of these specimens were negative on retesting at the reference laboratory. These results confirm the hypothesis; they demonstrate the need for quality control testing to avoid the misinterpretation of multicenter trials because of incorrect laboratory data. PMID:1929258

Krogstad, D J; Eveland, M R; Lim, L L; Volberding, P A; Sadler, B M

1991-01-01

227

Homemade Laser Show  

NSDL National Science Digital Library

With a laser pointer and some household items, learners can create their own laser light show. They can explore diffuse reflection, refraction and diffraction. The webpage includes a video which shows how to set up the activity and also includes scientific explanation. Because this activity involves lasers, it requires adult supervision.

Children's Museum of Houston

2011-01-01

228

Ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5alpha,8alpha-epidioxycholest-6-en-3beta-ol isolated from the mollusk Dolabrifera dolabrifera shows significant activity against Leishmania donovani.  

PubMed

An ecology- and bioassay-guided search employed to discover compounds with activity against tropical parasitic diseases and cancer from the opisthobranch mollusk, Dolabrifera dolabrifera, led to the discovery of antileishmanial properties in the known compound, 5alpha,8alpha-epidioxycholest-6-en-3beta-ol (1). Compound 1 was identified through nuclear magnetic resonance spectroscopy (1H, 13C) and mass spectrometry. The compound was concentrated in the digestive gland of D. dolabrifera, but was not detected in other body parts, fecal matter or mucus. Compound 1 showed an IC50 of 4.9 microM towards the amastigote form of Leishmania donovani compared with an IC50 of 281 microM towards the control Vero cell line, a 57.3-fold difference, and demonstrated no measurable activity against Plasmodium falciparum, Trypanosoma cruzi, and the breast cancer cell line, MCF-7. PMID:24427935

Clark, Kathryn E; Capper, Angela; Della Togna, Gina; Paul, Valerie J; Romero, Luz I; Johns, Timothy; Cubilla-Rios, Luis; Capson, Todd L

2013-11-01

229

The Diane Rehm Show  

NSDL National Science Digital Library

The Diane Rehm Show has its origins in a mid-day program at WAMU in Washington, D.C. Diane Rehm came on to host the program in 1979, and in 1984 it was renamed "The Diane Rehm Show". Over the past several decades, Rehm has played host to hundreds of guests, include Archbishop Desmond Tutu, Julie Andrews, and President Bill Clinton. This website contains an archive of her past programs, and visitors can use the interactive calendar to look through past shows. Those visitors looking for specific topics can use the "Topics" list on the left-hand side of the page, or also take advantage of the search engine. The show has a number of social networking links, including a Facebook page and a Twitter feed.

230

Producing Turkeys for Show  

E-print Network

. Use top-quality feeds. 4. Follow recommended management practices during the entire brooding and growing period. 5. Cull birds closely and select the show entry properly. Purchasing Poults Most youth livestock shows have rules and regulations governing... with an approved worm- ing compound. a73 Check turkeys monthly for parasites. Pay particular attention to skin around the vent area. Control external para- sites (lice, mites, etc.) with applications of Sevin ? dust. a73 Fire ants can cause skin blisters and must...

Thornberry, Fredrick D.

2005-12-14

231

Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs.  

PubMed Central

A lysine-to-arginine substitution at amino acid 65 (K65R) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is associated with resistance to 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI), and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC). To further characterize the molecular basis of such resistance, we expressed the pp6/p51 heterodimer of wild-type RT, K65R mutated RT, and a doubly mutated (K65R/M184V) RT in Escherichia coli and assessed the characteristics of nucleotide incorporation and chain termination in cell-free reverse transcription reactions in the presence and absence of various nucleoside triphosphate analogs. These reactions employed a HIV RNA template (HIV-PBS) that contained the primer binding sequence (PBS) and the U5 and R regions of HIV-1 genomic RNA and an oligodeoxynucleotide (dPR) complementary to the HIV-1 PBS as primer. The K65R and K65R/M184V RTs showed significantly decreased chain-termination effects during polymerization with the 5'-triphosphates of ddC, 3TC, 2',3'-dideoxyadenosine, and AZT (3'-azido-3'-deoxythymidine) in comparison with wild-type RT. Detailed analysis with ddCTP and wild-type RT revealed that chain termination occurred at all guanines in the RNA template. However, the frequency of dideoxynucleoside triphosphate (ddNTP)-induced chain termination was decreased at certain guanines but not others in reactions catalyzed by K65R RT. Both the K65R mutant RT and wild-type RT had similar processive activity. These results indicate that decreased chain termination of K65R RT in the presence of ddNTPs is consistent with data obtained in viral replication assays. Images Fig. 2 Fig. 3 Fig. 4 PMID:7535930

Gu, Z; Arts, E J; Parniak, M A; Wainberg, M A

1995-01-01

232

Complete republication: National Association of Medical Examiners position paper: Recommendations for the investigation, diagnosis, and certification of deaths related to opioid drugs.  

PubMed

The American College of Medical Toxicology and the National Association of Medical Examiners convened an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance. The panel finds the following: 1. A complete autopsy is necessary for optimal interpretation of toxicology results, which must also be considered in the context of the circumstances surrounding death, medical history, and scene findings. 2. A complete scene investigation extends to reconciliation of prescription information and pill counts. 3. Blood, urine, and vitreous humor, when available, should be retained in all cases. Blood from the femoral vein is preferable to blood from other sites. 4. A toxicological panel should be comprehensive and include opioid and benzodiazepine analytes, as well as other potent depressant, stimulant, and anti-depressant medications. 5. Interpretation of postmortem opioid concentrations requires correlation with medical history, scene investigation, and autopsy findings. 6. If death is attributed to any drug or combination of drugs (whether as cause or contributing factor), the certifier should list all the responsible substances by generic name in the autopsy report and on the death certificate. 7. The best classification for manner of death in deaths due to the misuse or abuse of opioids without any apparent intent of self-harm is "accident." Reserve "undetermined" as the manner for the rare cases in which evidence exists to support more than one possible determination. PMID:24132519

Davis, Gregory G

2014-03-01

233

Club Drugs  

MedlinePLUS

... of club drugs include Gamma hydroxybutyrate (GHB), Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Ketamine is a dissociative anesthetic, mostly used in veterinary ...

234

Showing What They Know  

ERIC Educational Resources Information Center

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

Cech, Scott J.

2008-01-01

235

Demonstration Road Show  

NSDL National Science Digital Library

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

Shropshire, Steven

2009-04-06

236

Hide / Show Animal Ethics  

E-print Network

the Ethics Secretariat for information on Animal Ethics Courses available at UNSW. All new added personnelHide / Show Animal Ethics Modification for Approved Application New personnel or updated role since last approval New person nominated since last approval You are here: Animal Ethics Application

New South Wales, University of

237

Stage a Water Show  

ERIC Educational Resources Information Center

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

Frasier, Debra

2008-01-01

238

What Do Maps Show?  

ERIC Educational Resources Information Center

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

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

239

The Ozone Show.  

ERIC Educational Resources Information Center

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

Mathieu, Aaron

2000-01-01

240

Show Me the Way  

ERIC Educational Resources Information Center

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

Dicks, Matthew J.

2005-01-01

241

Show-Me Magazine  

NSDL National Science Digital Library

Come along as the folks at the University of Missouri show you the history of their college days through the Show Me magazine. It's a wonderful collection of college humor published from 1946 to 1963. First-time visitors would do well to read about the magazine's colorful past, courtesy of Jerry Smith. A good place to start is the November 1920 issue (easily found when you browse by date), which contains a number of parody advertisements along with some doggerels poking good natured fun at the football team and an assortment of deans. Also, it's worth noting that visitors can scroll through issues and save them to an online "bookbag" for later use.

2008-01-01

242

Viewing television talk shows  

Microsoft Academic Search

We examined how motivation, audience activity, and attitudes influenced the likelihood of watching societal?issue and relational topics on television talk programs. Path analysis supported differences in ritualized and instrumental motives for watching talk shows. Information and exciting?entertainment motivation predicted greater’ realism of, affinity with, involvement with, and intent to watch talk television. Pass?time motivation predicted reduced affinity with and intent

Alan M. Rubin; Mary M. Step

1997-01-01

243

Mars Slide Show  

NASA Technical Reports Server (NTRS)

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

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

2006-01-01

244

New Drug Shows Mixed Results Against Early Alzheimer's  

MedlinePLUS

... Sharp People With Alzheimer’s at High Risk of Falls and Injury Can Vitamin B12 Help Ward Off Alzheimer’s? Heavy Smoking Increases Alzheimer’s Risk Fitness in a Flash: Exercise for Older Adults and Caregivers A Walk in the Park Senior-Friendly Fitness Close to Home Doing Crossword ...

245

UCSF Cancer Center Research Shows Promise of New Drugs  

Cancer.gov

Uncovering the network of genes regulated by a crucial molecule involved in cancer called mTOR, which controls protein production inside cells, researchers at the University of California, San Francisco (UCSF) have discovered how a protein “master regulator” goes awry, leading to metastasis.

246

American History Picture Show  

NSDL National Science Digital Library

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

Ms. Bennion

2009-11-23

247

Solar Light Show  

NSDL National Science Digital Library

Over the last few days, the Earth has been buffeted by a geomagnetic storm caused by a major solar flare. In addition to disruptions in radio, telecommunications, and electric service, the flare may also produce a dramatic light show as it peaks tonight. Weather permitting, the aurora borealis, or northern lights, may be visible as far south as Washington, D.C. The best viewing time will be local midnight. The sun is currently at the peak of its eleven-year solar cycle, spawning flares and "coronal mass ejections" (CME), violent outbursts of gas from the sun's corona that can carry up to 10 billion tons of electrified gas traveling at speeds as high as 2000 km/s. Geomagnetic storms result when solar winds compress the magnetosphere, sometimes interfering with electric power transmission and satellites, but also creating beautiful aurorae, as many stargazers hope will occur tonight.

de Nie, Michael Willem.

248

Show-Me Center  

NSDL National Science Digital Library

The Show-Me Center, located at the University of Missouri, is a math education project of the National Science Foundation. The center's Web site "provides information and resources needed to support selection and implementation of standards-based middle grades mathematic curricula." There are some sample lesson plans offered, but most of the material is solely for use by teachers. Five different middle grade math curriculums were started in 1992, and now, the implementation and results of each curriculum are presented on this site. Teachers can examine each one, view video clips, and read case studies and other reports to choose which parts of the curriculums would fit best into their own classes.

249

Drugs, drugs--who has the drugs?  

PubMed

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

Blair, James

2012-01-01

250

Public medical shows.  

PubMed

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

Walusinski, Olivier

2014-01-01

251

The drug cocktail network  

PubMed Central

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

2012-01-01

252

Antitumor drugs as photochemotherapeutic agents  

NASA Astrophysics Data System (ADS)

Irradiation with 86 J/cm2 of cultures of Fisher-rate thyroid cells (FRTL5) in the presence of daunomycin derivatives at wavelengths between 488 and 595 nm i.e., in the visible- absorption bands of these drugs, is shown to enhance their cytotoxicity. Daunomycin, its 4- demethoxy derivative, 5-iminodaunomycin, and two amino-substituted 4-demethoxy derivatives of daunomycin are tested. While a 2-h exposure to the drugs in the dark produces 50 short-term cell mortality at dosages (LD50) in the range 23 to 138 (mu) g/ml, irradiation administered during the cell exposure to the drugs is found to lower the LD50 values down to the range 45 to 289 ng/ml. Furthermore, while the LD50 values for all drugs in the absence of photoactivation are similar, if light is administered those for the 4- demethoxy compounds are lowered by 3 orders of magnitude and those for the other derivatives by 2 orders of magnitude. Microfluorimetric investigations reveal that photoactivation causes fading of the drug fluorescence in the perinuclear cytoplasm. The effect is more pronounced for drugs with higher photosensitizing properties. The nonfluorescent photoproducts which are formed in the cells during photoactivation exhibit a cytotoxic activity that is, at long term, lower than that of the original drug. The authors cannot yet assess which excited-state property of anthracyclines plays the key role in the photosensitized reaction(s) responsible for both short-term cell kill and long-term toxic effects. The show, however, that such property is strongly affected by the removal of the methoxy group from the C4 position.

Andreoni, Alessandra; Colasanti, Alberto; Kisslinger, Annamaria; Malatesta, Vincenzo; Mastrocinque, Michele; Roberti, Giuseppe

1991-11-01

253

Positive Lives  

NSDL National Science Digital Library

The Positive Lives project is "a unique international project that photographs and documents the social and emotional impact of the global HIV/AIDS epidemic, illuminating positive human responses to this world crisis." Sponsored by the Levi Strauss Foundation and the Terrence Higgins Trust, the project has sponsored photographers from across the world to photograph various persons living with HIV/AIDS in a host of very different settings. While the project has sponsored a number of various photographic exhibits, this online collection represents a small portion of the work thus far. Using an interactive map of the world, users can click on different geographic areas to view photographic exhibits documenting the lived experience of this condition. In South Africa, visitors can learn about the work and the residents of Nazareth House, which is a children's home in Cape Town taking care of abandoned children with HIV or AIDS. In Edinburgh, visitors are taken through the lives of young drug abusers at the Muirhouse Estate who are also living with either HIV or AIDS. In the words of photographer John Sturrock, "In Muirhouse I witnessed the emotional struggle of people enduring a tragedy..." However, hope is present in these photographic essays as well, as they represent a broad range of emotions.

254

The Great Cometary Show  

NASA Astrophysics Data System (ADS)

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

2007-01-01

255

The prevalence of drugs in injured drivers.  

PubMed

In mid 2009 Victoria introduced compulsory drug testing of blood taken from all injured drivers taken to hospital. ?(9)-Tetrahydrocannabinol (THC), methylamphetamine (MA) and 3,4-methylenedioxy-methylamphetamine (MDMA) are prohibited and if drivers are positive to any amount an automatic penalty is enforced. Laboratory screens were conducted on preserved blood using ELISA testing for cannabis metabolite and methylamphetamines and a fully validated LC-MS/MS method for 105 drugs including THC, amphetamines, opioids, benzodiazepines, antidepressants and antipsychotics and a number of other psychoactive substances using a minimum of two transitions per drug. Conventional GC-testing for ethanol was used to screen and quantify the presence of alcohol. 1714 drivers were tested and showed alcohol in 29% (? 0.01 g/100mL) and drugs in 35%. The positive rate for the three drugs prohibited by legislation was 12.5%. The prevalence of THC, MA and MDMA was 9.8%, 3.1%, and 0.8%, respectively. The range of THC concentrations in blood was 2-42 ng/mL (median 7) of which 70% had a concentration of 10 ng/mL or higher. The range of concentrations for MA and MDMA was 0.02-0.4 and 0.03-0.3mg/L (median for both drugs was 0.05 mg/L). Drugs of any type were detected in 35% of cases. The other drugs were largely prescribed drugs such as the antidepressants (9.3%) and benzodiazepines (8.9%). Neither 6-acetylmorphine nor cocaine (or benzoylecgonine) was detected in these cases. PMID:21377816

Drummer, Olaf H; Kourtis, Irene; Beyer, Jochen; Tayler, Penny; Boorman, Martin; Gerostamoulos, Dimitri

2012-02-10

256

Redefining America's "War on Drugs"  

E-print Network

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

McQuade, D. Tyler

257

Microfluidic device for drug delivery  

NASA Technical Reports Server (NTRS)

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

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

2010-01-01

258

Offered: Offered: Position(s): Position(s)  

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description.gza.com, to view a listing of current open positions. Resumes may also be sent to humanresources@gza.com GZA

New Hampshire, University of

259

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

PubMed Central

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

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

2014-01-01

260

Drug allergies  

MedlinePLUS

... Most drug allergies cause minor skin rashes and hives. Serum sickness is a delayed type of drug ... allergic reaction. For example, aspirin can cause nonallergic hives or trigger asthma . Some drug reactions are considered ...

261

Club Drugs  

MedlinePLUS

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

262

Drug abuse  

MedlinePLUS

Substance abuse; Illicit drug abuse; Narcotic abuse; Hallucinogen abuse ... damage ( peripheral neuropathy ) Sudden death OPIATES, OPIOIDS, AND NARCOTICS Opiates come from opium poppies. These drugs include ...

263

Maximum entropy principle for predicting response to multiple-drug exposure in bacteria and human cancer cells  

NASA Astrophysics Data System (ADS)

Drugs are commonly used in combinations larger than two for treating infectious disease. However, it is generally impossible to infer the net effect of a multi-drug combination on cell growth directly from the effects of individual drugs. We combined experiments with maximum entropy methods to develop a mechanism-independent framework for calculating the response of both bacteria and human cancer cells to a large variety of drug combinations comprised of anti-microbial or anti-cancer drugs. We experimentally show that the cellular responses to drug pairs are sufficient to infer the effects of larger drug combinations in gram negative bacteria, Escherichia coli, gram positive bacteria, Staphylococcus aureus, and also human breast cancer and melanoma cell lines. Remarkably, the accurate predictions of this framework suggest that the multi-drug response obeys statistical rather than chemical laws for combinations larger than two. Consequently, these findings offer a new strategy for the rational design of therapies using large drug combinations.

Wood, Kevin; Nishida, Satoshi; Sontag, Eduardo; Cluzel, Philippe

2012-02-01

264

Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma  

PubMed Central

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

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

2013-01-01

265

Comparison of Attitudes, Knowledge and Drug Abuse Among Military Offenders  

ERIC Educational Resources Information Center

Military offenders' (N=69) attitudes towards drugs, knowledge about drugs, and reported drug abuse histories were analyzed. Results indicated a significantly positive relationship between all three variables. Military offenders who had drug use histories also had more liberal attitudes toward drug use and a greater degree of knowledge about drugs.…

Ratliff, Bascom W.

1977-01-01

266

Drug Facts  

MedlinePLUS Videos and Cool Tools

... this page Hear and read a story about drug treatment. Take a quiz : What do you know about drugs? Haga clic aquí para información sobre el abuso ... y tratamiento. VIDEO: Anyone Can Become Addicted to Drugs VIDEO: Why Are Drugs So Hard to Quit? ...

267

Generic Drugs  

MedlinePLUS

What is a generic drug? A generic is a copy of a brand-name drug. A brandname drug has a patent. When the patent ... Celebrex. But oft en you can get a generic drug that works just as well— and costs much ...

268

Drug Views  

Microsoft Academic Search

Substance abuse is a significant social problem and political issue. Students at a Midwestern university were surveyed on their drug views. The findings suggest that race is a statistically significant factor on students' views toward drugs. White students were more likely than non-Whites to view drugs as a pressing social issue, to consider drug use as a character weakness, and

Eric G. Lambert; Lois A. Ventura; David N. Baker; Morris Jenkins

2006-01-01

269

Adolescent Drug Use and Educational Attainment  

Microsoft Academic Search

Recent studies investigating the labor-market effects of illicit drug use have consistently found a positive relation between drug use and earnings. These analyses have, however, ignored the potential relationship between drug use and human-capital formation. This paper examines the effect of drug use during adolescence on formal educational attainment using a sample drawn from the National Longitudinal Survey Youth Cohort.

Charles Register; Donald Williams; Paul Grimes

2001-01-01

270

Offered: Offered: Position(s): Position(s)  

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description Center Liberty Mutual Insurance Bachelors Liberty Mutual offers entry level positions into 9 different functions. Each position differents depending on the specific function Liberty Mutual offers entry level

New Hampshire, University of

271

Offered: Offered: Position(s): Position(s)  

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description to fill current Trooper positions, with potential additional opportunities during ones' career job postingsDescription of positions vary www.nh.gov Law Enforcement Company Overview: Degree: Unpaid

New Hampshire, University of

272

The Role of Cavitation in Acoustically Activated Drug Delivery  

PubMed Central

Pluronic P105 micelles are potential candidates as chemotherapy drug delivery vehicles using ultrasonic stimulation as a release trigger. Acoustic power has been previously shown to release two anthracycline agents from these polymeric carriers. In this study, an ultrasonic exposure chamber with fluorescence detection was used to examine the mechanism of doxorubicin release from P105 micelles. Acoustic spectra were collected and analyzed, at the same spatial position as fluorescence data, to probe the role of cavitation in drug release. Our study showed a strong correlation between percent drug release and subharmonic acoustic emissions, and we attribute the drug release to collapse cavitation that perturbs the structure of the micelle and releases drug. PMID:16046023

Husseini, Ghaleb A.; Diaz de la Rosa, Mario A.; Richardson, Eric S.; Christensen, Douglas A.; Pitt, William G.

2006-01-01

273

Homelessness and drug misuse in developing countries: A mathematical approach  

NASA Astrophysics Data System (ADS)

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

Bhunu, C. P.

2014-06-01

274

The Economics of Preemployment Drug Testing  

Microsoft Academic Search

A labor market matching model shows that preemployment drug testing leads to a net improvement in social welfare, but the overall level of drug testing will exceed the social optimum. These results hold for wide ranges of parameter values. Drug testing results in fewer and shorter episodes of unemployment for drug-free workers while producing the opposite effect for drug users.

Jason Zimmerman

2002-01-01

275

In silico modeling to predict drug-induced phospholipidosis  

SciTech Connect

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

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

2013-06-01

276

Patents Associated with High-Cost Drugs in Australia  

PubMed Central

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

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

2013-01-01

277

Students' View Of School Drug Use  

ERIC Educational Resources Information Center

The purpose of this investigation was to determine students' perception of their drug use activity and desired treatment. Findings indicate the existence of a positive relationship between student poly-drug use and socioeconomic status. (Author)

Farkas, Marshall I.

1974-01-01

278

Who Tests which Athletes for What Drugs?  

ERIC Educational Resources Information Center

This article reviews trends in sports organizations' drug testing policies and procedures for its members, including which drugs are tested, who gets tested within the organizations, when tests are conducted, and penalties for those who test positive. (CB)

Gall, Sarah L.; And Others

1988-01-01

279

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

E-print Network

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

Gross, Louis J.

280

Drug Resistance  

MedlinePLUS

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

281

Drug Interactions  

MedlinePLUS

... involve the liver. Several drugs slow down or speed up the action of liver enzymes. This can ... www.drugdigest.org/wps/portal/ddigest THE BOTTOM LINE Many ARVs can interact with other medications, drugs, ...

282

Drug Control  

ERIC Educational Resources Information Center

This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

Leviton, Harvey S.

1975-01-01

283

Hazardous Drugs  

MedlinePLUS

... Solutions Possible Solutions Additional Information Safety and Health Topics A-Z Index What's New Worker exposure to ... in the workplace. Pharmacy . Reviews safety and health topics related to hazardous drugs including drug handling, administration, ...

284

Drug Cravings  

NSDL National Science Digital Library

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

Science Update

2003-07-14

285

POSTDOCTORAL POSITION IN NANOTECHNOLOGY & NEUROENGINEERING RESEARCH  

E-print Network

POSTDOCTORAL POSITION IN NANOTECHNOLOGY & NEUROENGINEERING RESEARCH AT UNIVERSITY OF CALIFORNIA, DAVIS A postdoctoral position is available immediately at University of California, Davis-interfaces for diagnostic and therapeutic applications, including biosensors for neurotoxins and advanced drug delivery

Seker, Erkin

286

GWAS and drug targets  

PubMed Central

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

2014-01-01

287

Alcohol, Drugs and Young Drivers.  

ERIC Educational Resources Information Center

This paper reviews the research literature on the relationship of drugs, alcohol, and driving among young people, university students, and a group of young criminals. The data show that young people use drugs more than adults do, and that they drive under the influence of drugs or alcohol, especially at night, more often than adults do, and…

Voas, Robert B.

288

Positive Psychology  

ERIC Educational Resources Information Center

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

Peterson, Christopher

2009-01-01

289

Offered: Offered: Position(s): Position(s)  

E-print Network

: Software Engineer (embedded systems), Java Developer, SAP techno/functional analyst, Web Developer, Systems -- 12:00-4:00pm Yes Software Engineer, Web Developer, Network Administrator, Systems Engineer, SoftwareCompany: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description

New Hampshire, University of

290

Offered: Offered: Position(s): Position(s)  

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description's easy to see you'll be a manager at this multibillion dollar industry leader some day. At Enterprise you't be a glorified gopher getting coffee or filing all day. Our interns go at the same energized pace and take

New Hampshire, University of

291

Offered: Offered: Position(s): Position(s)  

E-print Network

decision-making skills -Assertiveness and initiative -Team-oriented thinking -Ability to communicateCompany: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description Target Bachelors, Masters Use your business, leadership and people skills to inspire exceptional

New Hampshire, University of

292

Information for Consumers (Drugs)  

MedlinePLUS

... FDA Information on FDA-approved brand name and generic drugs MedlinePlus: Drugs Consumer drug information from the National ... Approved Drugs Side Effects Treatments for Medical Problems Generic Drugs Prescription Drugs and Over-the-Counter (OTC) Drugs ...

293

[Drug-drug interaction of antifungal drugs].  

PubMed

This article reviews the in vitro metabolic and the in vivo pharmacokinetic drug-drug interactions with antifungal drugs, including fluconazole, itraconazole, micafungin, miconazole, and voriconazole. In the in vitro interaction studies, the effects of antifungal drugs on specific activities of cytochrome P450s (CYPs), including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, in human liver microsomes are compared to predict the possibility of drug interactions in vivo. Fluconazole, micafungin, and voriconazole have lower inhibitory effects on CYP3A4 activities than itraconazole and miconazole, and IC(50) and/or K(i) values against CYP2C9 and CYP2C19 activities are the lowest for miconazole, followed by voriconazole and fluconazole. In in vivo pharmacokinetic studies, it is well known that itraconazole is a potent clinically important inhibitor of the clearance of CYP3A4 substrates, and fluconazole and voriconazole are reported to increase the blood or plasma concentrations of not only midazolam and cyclosporine (CYP3A4 substrates) but also of phenytoin (CYP2C9 substrate) and/or omeprazole (CYP2C19/CYP3A4 substrate). On the other hand, no inhibition of CYP activities except for CYP3A4 activity by micafungin is observed in vitro, and the blood concentrations of cyclosporine and tacrolimus are not affected by coadministration of micafungin in vivo, suggesting that micafungin would not cause clinically significant interactions with drugs that are metabolized by CYPs via the inhibition of metabolism. Miconazole is a potent inhibitor of all CYPs investigated in vitro, although there are few detailed studies on the clinical significance of this except for CYP2C9. Therefore the differential effects of these antifungal drugs on CYP activities must be considered in the choice of antifungal drugs in patients receiving other drugs. PMID:16205037

Niwa, Toshiro; Shiraga, Toshifumi; Takagi, Akira

2005-10-01

294

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

PubMed Central

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

Kurzban, Robert; Dukes, Amber; Weeden, Jason

2010-01-01

295

Scaring Kids' Shows Off TV.  

ERIC Educational Resources Information Center

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

Raspberry, William

1980-01-01

296

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

Federal Register 2010, 2011, 2012, 2013, 2014

...Generic drugs approved under an abbreviated new...data show that only 10 percent of generic drug labeling has been converted to...prescriptions today are filled with generic drugs,\\6\\ FDA believes that it...

2013-02-06

297

Positive tensor factorization  

Microsoft Academic Search

A novel fixed point algorithm for positive ten- sor factorization (PTF) is introduced. The update rules efficiently minimize the reconstruction error of a positive tensor over positive factors. Tensors of arbitrary order can be factorized, which extends earlier results in the lit- erature. Experiments show that the factors of PTF are easier to interpret than those produced by methods based

Max Welling; Markus Weber

2001-01-01

298

2013 Goat Shows Show Date Show Name Entries Due Eligibility Weigh In Show Time Contact Phone Extra Info  

E-print Network

2013 Goat Shows Show Date Show Name Entries Due Eligibility Weigh In Show Time Contact Phone Extra/13/2013 Cannon Co. Day of Show Youth Must 8 a.m. to 12 p.m. Carol 615-563-5260 Bring own Jr. Goat $1.00 a head Control 10 a.m. Melton Bedding Association Goat 7/20/2013 Overton Co. Day of Show Youth Before 5 p.m. 6

Grissino-Mayer, Henri D.

299

TRAIL shows potential cardioprotective activity.  

PubMed

Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated that TRAIL (administrated as either recombinant soluble TRAIL or as AAV-TRAIL expression viral vector) reduced the development of cardiomyopathy in the ApoE(-/-) diabetic mouse model. These data suggest, for the first time, that therapeutically administration of TRAIL might have a cardioprotective effect. PMID:21197620

Toffoli, Barbara; Bernardi, Stella; Candido, Riccardo; Zacchigna, Serena; Fabris, Bruno; Secchiero, Paola

2012-06-01

300

Drug Rash (Unclassified Drug Eruption) in Adults  

MedlinePLUS

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

301

Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis  

PubMed Central

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

Balachandran, Ram K.

2011-01-01

302

Comparison of drug abuse in different military populations.  

PubMed

Quantitative analytical data, generated at the Navy Drug Screening Laboratory, Great Lakes, Illinois, expressed as percent confirmed positives for four drugs of abuse (marijuana metabolite, cocaine metabolite, amphetamines, and opiates) are summarized and compared according to their population of origin. The four populations of interest included U.S. Navy and Marine Corps recruits and service school members. Conformed positive urines for marijuana showed a small but significant decline (p less than 0.001) from about 1.2% confirmed positive among U.S. Navy recruits entering service school commands in 1984 to 0.9% among Navy service school members in 1988 and from 2.0% among U.S. Marine Corps recruits entering service schools in 1984 to 0.8% among Marine Corps service school members in 1988. Navy and Marine Corps recruits showed a significantly higher (p less than 0.001) confirmed positive use rate (6.1 and 3.3%, respectively) compared to service school members, perhaps reflecting their recent civilian use pattern. The relatively high confirmed positive cocaine rate among all groups may have reflected an increasing trend in all populations, confirming a similar trend in high school and other civilian populations. Generally, the frequency of confirmed positive urines with amphetamines and opiates, based upon the findings at the Navy Drug Screening Laboratory at Great Lakes, has been static except for an apparent recent increase in amphetamine use in 1988. The decline in confirmed positive drug urinalyses among service school members from both the Navy and Marine Corps indicated that perhaps education and maturity had a positive effect upon their behavior. PMID:2760588

Needleman, S B; Romberg, R W

1989-07-01

303

Show Them You Really Want the Job  

ERIC Educational Resources Information Center

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

Perlmutter, David D.

2012-01-01

304

Drug Research  

NASA Technical Reports Server (NTRS)

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

1989-01-01

305

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

PubMed Central

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

Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

2013-01-01

306

Nursing Positions  

MedlinePLUS

... cross-cradle position allows you to have more control over how your baby latches on. Many moms find that they're able to get their babies latched on more deeply with this hold. Continue The Side-Lying Position This position is comfortable for mothers who've had a cesarean section (C-section) ...

307

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

PubMed Central

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

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

2010-01-01

308

PfalDB: an integrated drug target and chemical database for Plasmodium falciparum.  

PubMed

Plasmodium falciparum is one of the deadliest protozoan parasite species among those that cause malaria. Uncontrolled use of antimalarial drugs has resulted in evolutionary selection pressure favoring high levels of resistance to antimalarials; currently P.falciparum shows resistance to all classes of antimalarials. Therefore it is essential to identify novel drug targets, and design selective anti-malarials which can overcome resistance. While many drug targets are freely available in various public domain resources, a single comprehensive source of data containing easily searchable and retrievable information is currently lacking. To facilitate the total integration and mining of data emerging from different drug consortia and also to prioritize drug targets for structure-based drug design, an open-access, inclusive comprehensive database for Plasmodium falciparum was established. Meta data of known/modeled structures along with binding site parameters of drug targets have been included in the database. Additionally, chemical compounds showing a positive inhibitory assay against Plasmodium falciparum or known drug targets have also been provided. The database is accessible at http://pfaldb.jnu.ac.in. The database provides diverse information regarding the structure, sequence, stage specific gene expression, pathway, action mechanism, essentiality and druggability for each drug target, and literature to assess the validation status of individual drug targets. It also includes information on individual anti-malarials with their activity and bioassay. PMID:25198774

Kumar, Amit; Agarwal, Nidhi; Pant, Lalit; Singh, Jay Prakash; Ghosh, Indira; Subbarao, Naidu

2014-01-01

309

[A case of drug eruption induced by hydroxyzine pamoate].  

PubMed

A 62-year-old woman with rheumatoid arthritis, Basedow's disease and arrhythmia has been treated with antirheumatic, antiarrhythmic drugs and so on. She developed pruritic diffuse erythema with papules on the trunk and extremities 2 days after taking hydroxyzine pamoate for asteatotic eczema. Laboratory data showed increased levels of eosinophils. Histopathological examination revealed a infiltrate of inflammatory cells in the upper dermis. Patch tests with hydroxyzine pamoate and hydroxyzine hydrochloride were positive. From these findings, we diagnosed this case as drug eruption due to hydroxyzine. Her eruption subsided after she discontinued hydroxyzine pamoate and other drugs which were started within 5 days before the onset of the eruption and was treated with systemic steroid, systemic antiallergic drug and topical steroid. PMID:16671329

Tamagawa, Risa; Katoh, Norito; Nin, Megumi; Kishimoto, Saburo

2006-01-01

310

[Drug dependence and psychotropic drugs].  

PubMed

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

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

1994-11-01

311

Managing Beef Cattle for Show  

E-print Network

This publication gives advice on raising beef cattle to exhibit at shows. Topics include animal selection, feeding, general health management, disease prevention, calf handling, and preparing for the show....

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

2001-11-16

312

What Do Blood Tests Show?  

MedlinePLUS

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

313

Asia: Showing the Changing Seasons  

NSDL National Science Digital Library

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

Jesse Allen

1998-09-09

314

[Drugs and occupational accident].  

PubMed

In a case of a fatal occupational accident (construction worker, fall from roof, urine test positive for cocaine and THC, e.g. cannabis) the question arised to what extent those drug-related occupational accidents occur. In the literature only few cases, mainly dealing with cannabis influence, have been reported, however, a higher number is suspected. Cocaine and other stimulating drugs (amphetamine) are more often used to increase physical fitness. By direct or indirect interference with vigilance these compounds may provoke accidents. Due to the lack of a legal basis proving of the influence of drugs at the working place is still very limited, although highly sensitive chemical-toxicological assay procedures are available to detect even the chronic abuse (in hair). In the general conditions of accident insurances a compensation is excluded when alcohol is involved, but drugs are not mentioned. It is indeed difficult to establish a concentration limit for drugs like that existing for alcohol (1.1%). In each case the assay of the drug involved and exact knowledge of its specific effects is in an essential prerequisite to prove the causal relationship. PMID:8852068

Bratzke, H; Albers, C

1996-02-01

315

Random Drug Tests: What Are the Costs?  

ERIC Educational Resources Information Center

American Trucking Association conducted survey of 1,655 motor carriers 2 years ago concerning drug use in trucking industry. Based on responses from 540 carriers (32%) costs of drug testing ranged between $30 and $70 per test. Of 153,000 truck drivers tested, 1.95% were verified "positive" for illegal drug use. Delaware study of school bus drivers…

Paul, William E.

1993-01-01

316

ELI Talent Show Final Exams  

E-print Network

Highlights ELI Talent Show Final Exams Scholarship Nominees Graduate Admissions Workshop Reminders from the Office Manners, Cultures, & Grammar TheELIWeekly ELI Talent Show It's going to be a blast! Come one, come all! The 2nd Annual ELI Talent Show will be on Tuesday, April 15th

Pilyugin, Sergei S.

317

Drug Testing.  

ERIC Educational Resources Information Center

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

Legal Memorandum, 1987

1987-01-01

318

Drug Education.  

ERIC Educational Resources Information Center

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

Sardana, Raj K.

319

Antineoplastic Drugs  

NASA Astrophysics Data System (ADS)

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

Sadée, Wolfgang; El Sayed, Yousry Mahmoud

320

Micro-Fluidic Device for Drug Delivery  

NASA Technical Reports Server (NTRS)

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

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

2014-01-01

321

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

ERIC Educational Resources Information Center

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

Office of National Drug Control Policy, 2007

2007-01-01

322

Offered: Offered: Position(s): Position(s)  

E-print Network

on merit, quailifications, and abilities. Jacobs TEIMS does not discriminate in employment opportunities or practices on the basis of: race, color, religion, gender, national origin, age, sexual orientation, gender)337-2500 or careers@tybrin.com to be considered for reasonable accommodation. Jacobs TEIMS is a Drug-Free workplace

New Hampshire, University of

323

Systems pharmacology augments drug safety surveillance.  

PubMed

Small molecule drugs are the foundation of modern medical practice, yet their use is limited by the onset of unexpected and severe adverse events (AEs). Regulatory agencies rely on postmarketing surveillance to monitor safety once drugs are approved for clinical use. Despite advances in pharmacovigilance methods that address issues of confounding bias, clinical data of AEs are inherently noisy. Systems pharmacology-the integration of systems biology and chemical genomics-can illuminate drug mechanisms of action. We hypothesize that these data can improve drug safety surveillance by highlighting drugs with a mechanistic connection to the target phenotype (enriching true positives) and filtering those that do not (depleting false positives). We present an algorithm, the modular assembly of drug safety subnetworks (MADSS), to combine systems pharmacology and pharmacovigilance data and significantly improve drug safety monitoring for four clinically relevant adverse drug reactions. PMID:25670520

Lorberbaum, T; Nasir, M; Keiser, M J; Vilar, S; Hripcsak, G; Tatonetti, N P

2015-02-01

324

Towards better patient care: drugs to avoid.  

PubMed

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

2013-04-01

325

[Club drugs].  

PubMed

Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse. PMID:22525626

Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

2011-01-01

326

Planning a Successful Tech Show  

ERIC Educational Resources Information Center

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

Nikirk, Martin

2011-01-01

327

Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulation  

PubMed Central

Background Development of anticancer drugs is challenging. Indeed, much research effort has been spent in the development of new drugs to improve clinical outcomes with minimal toxicity. We have previously reported that a formulation of lipid gold porphyrin nanoparticles reduced systemic drug toxicity when compared with free gold porphyrin. In this study, we investigated the delivery and treatment efficiency of PEG surface-modified lipid nanoparticles as a carrier platform. Methods We encapsulated antitumor drugs into PEG-modified lipid nanoparticles and these were characterized by size, zeta potential, and encapsulation efficiency. The delivery efficiency into tumor tissue was evaluated using a biodistribution study. To evaluate antitumor efficacy, gold porphyrin or camptothecin (a DNA topoisomerase I inhibitor) were encapsulated and compared using an in vivo neuroblastoma (N2A) model. Results We showed that drug encapsulation into PEG-modified lipid nanoparticles enhanced the preferential uptake in tumor tissue. Furthermore, higher tumor killing efficiency was observed in response to treatment with PEG-modified lipid nanoparticles encapsulating gold porphyrin or camptothecin when compared with free gold porphyrin or free camptothecin. The in vivo antitumor effect was further confirmed by study of tumor inhibition and positive apoptosis activity. Surface modification of lipophilic nanoparticles with PEG increased the efficiency of drug delivery into tumor tissue and subsequently more effective antitumor activity. Conclusion This specific design of a chemotherapeutic agent using nanotechnology is important in the development of a safe and effective drug in cancer therapy. PMID:22359452

Lee, Puiyan; Zhang, Ruizhong; Li, Vincent; Liu, Xuelai; Sun, Raymond WY; Che, Chi-Ming; Wong, Kenneth KY

2012-01-01

328

In silico modeling to predict drug-induced phospholipidosis.  

PubMed

Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure-activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80-81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ?80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. PMID:23541745

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

2013-06-01

329

Positive Psychotherapy  

ERIC Educational Resources Information Center

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

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

2006-01-01

330

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

PubMed

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

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

2014-09-01

331

Using Graphs to Show Connections  

NSDL National Science Digital Library

The purpose of this resource is to show how graphs of GLOBE data over time show the interconnectedness of Earth's system components at the local level. Students visit a study site, where they observe and recall their existing knowledge of air, water, soil, and living things to make a list of interconnections among the four Earth system components. They make predictions about the effects of a change in a system, inferring ways these changes affect the characteristics of other related components.

The GLOBE Program, University Corporation for Atmospheric Research (UCAR)

2003-08-01

332

Club Drugs  

MedlinePLUS

... concerts, and parties. Club drugs include GHB, Rohypnol®, ketamine, and others. MDMA (Ecstasy) , Methamphetamine , and LSD (Acid) , ... Graders 12th Graders GHB Past Year - - 1.00 Ketamine Past Year - - 1.50 Rohypnol Lifetime 0.60 ...

333

Prescription Drugs  

MedlinePLUS

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

334

Antiplatelet Drugs  

MedlinePLUS

... to Help Prevent a Heart Attack or Stroke? Aspirin is an antiplatelet drug. It is used regularly to help prevent blood clots. • Blood clots in your legs • Family history of heart disease • Heart attack or stroke in ...

335

Drug allergy  

PubMed Central

Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

Warrington, Richard

2012-01-01

336

Drug-Drug Interactions: Antiretroviral Drugs and Recreational Drugs.  

PubMed

With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take people take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrate of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reverse-transcriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but shown several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs. PMID:25429704

Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

2014-11-26

337

Glioma-associated endothelial cells show evidence of replicative senescence  

SciTech Connect

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

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

2007-04-01

338

National Orange Show Photovoltaic Demonstration  

SciTech Connect

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

Dan Jimenez (NOS)Sheri Raborn, CPA (National Orange Show); Tom Baker (California Construction Authority)

2008-03-31

339

Positive emotions Some positive emotions  

E-print Network

Friendship Fulfillment Generosity Happiness Hope Joy Love Loyalty Passion Playfulness Pride Relief content, recording instances of happiness, interest, love and hope. They found that nuns who expressed hypothesis of positive emotions Fredrikson, 2003, Amer Sci, 91, 330-335. #12;Animal models of positive

Cooper, Brenton G.

340

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

PubMed Central

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

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

2014-01-01

341

Diarrheal Disease in Show Swine  

E-print Network

D iarrhea is one of the most important problems in show pigs. It can occur at any time, from first obtaining a show pig through the last day of exhi- bition. It can become a chronic condition that persists for weeks. Diarrhea can be caused..., in itself, cause loose stools or diarrhea. If a pig is grow- ing well but has a chronically loose stool, reduce the pro- tein and/or increase fiber in the diet. If the stool does not firm up, there are probably other causes of diarrhea. Parasitic Causes...

Lawhorn, D. Bruce

2007-02-27

342

Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle  

E-print Network

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

Zhang, Liangfang

343

Towards global network positioning  

Microsoft Academic Search

We propose a new approach to predict Internet network distance called Global Network Positioning (GNP). This approach models the Internet as a geometric space and distributedly computes geometric coordinates to characterize the positions of hosts in the Internet. By conducting Internet experiments, we show that the geometric distances implied by the GNP hosts coordinates can accurately predict the Internet network

T. S. Eugene Ng; Hui Zhang

2001-01-01

344

Midterm Picnic ELI Talent Show  

E-print Network

Highlights Midterm Picnic ELI Talent Show Notes from the Office Birthdays Manners Grammar The the new ELI students. All ELI students, staff, and friends are invited to the Midterm/Welcome picnic Where: Broward Beach (Behind Broward and Yulee Halls, across 13th Street from the ELI). What to Bring

Pilyugin, Sergei S.

345

Producing Talent and Variety Shows.  

ERIC Educational Resources Information Center

Identifies key aspects of producing talent shows and outlines helpful hints for avoiding pitfalls and ensuring a smooth production. Presents suggestions concerning publicity, scheduling, and support personnel. Describes types of acts along with special needs and problems specific to each act. Includes a list of resources. (MJP)

Szabo, Chuck

1995-01-01

346

Radiographic positioning  

SciTech Connect

This book concentrates on the routine radiographic examinations commonly performed. It details the wide variety of examinations possible and their place in initial learning and in the radiology department as references for those occasions when an unusual examination is requested. This book provides information ranging from basic terminology to skeletal positioning to special procedures. Positions are discussed and supplemented with a picture of a patient, the resulting radiograph, and a labeled diagram. Immobilization and proper shielding of the patient are also shown.

Eisenberg, R.L.; Dennis, C.A.; May, C.

1989-01-01

347

DRUG NAME (INSERT DRUG NAME)  

Cancer.gov

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

348

Targeted Agents Active Against HER2-positive Breast Cancer: Questions and Answers  

Cancer.gov

ALTTO was a clinical trial designed to determine whether the combination of the monoclonal antibody trastuzumab (Herceptin) and the drug lapatinib (Tykerb) was more effective in treating HER2/ErbB2-positive breast cancer when combined with chemotherapy than either agent alone. Results from ALTTO did not show additional benefit from combining lapatinib and trastuzumab compared with trastuzumab treatment alone.

349

Drug signs and teenagers  

MedlinePLUS

... and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... Elsevier Saunders; 2011:chap 108. National Institute on Drug Abuse: Preventing drug use among children and adolescents. NIH ...

350

Drug Tolerance in Mycobacterium tuberculosis  

Microsoft Academic Search

Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between myco- bacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human

ROBERT S. WALLIS; SHRIPAD PATIL; SEON-HEE CHEON; KAY EDMONDS; MANIJEH PHILLIPS; MARK D. PERKINS; MOSES JOLOBA; ALICE NAMALE; JOHN L. JOHNSON; LUCILEIA TEIXEIRA; REYNALDO DIETZE; SALMAN SIDDIQI; ROY D. MUGERWA; KATHLEEN EISENACH

351

Other Drugs  

E-print Network

n The number of anabolic agents and other selected hormones detected at the Australian border in 2007–08 is the highest on record. n National steroid seizures decreased by 32 per cent in weight, while the number increased by 14 per cent. n National tryptamine seizures increased in weight and number in 2007–08. n The number of ketamine border detections has continued to increase since 2004–05. Anabolic agents and selected hormones Main forms The Australian Standard Classification of Drugs of Concern distinguishes four classes of substances defined as anabolic agents and selected hormones. These are anabolicandrogenic steroids (AAS); beta?2 agonists; peptide hormones, mimetics and analogues; and other anabolic agents and selected hormones (ABS, 2000). The large number of drugs in this category are commonly referred to as performance and image enhancing drugs (PIEDs). Anabolic agents

Key Points

352

Rocks and Minerals Slide Show  

NSDL National Science Digital Library

This interactive slide show of common rocks and minerals allows students to choose from two sets of minerals and click on a thumbnail to see a larger photograph with a full description of the mineral including color, streak, hardness, cleavage/fracture, and chemical composition. Also included are its use and where it is found. The rocks are divided into igneous, sedimentary, and metamorphic and can be accessed in the same manner. They are described on the basis of crystal size and mineral composition as well as use.

353

Position indicator  

DOEpatents

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

Tanner, David E. (Poway, CA)

1981-01-01

354

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

PubMed Central

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

2010-01-01

355

Oral lichenoid drug reaction associated with antihypertensive and hypoglycemic drugs.  

PubMed

Oral lichen planus and oral lichenoid drug reactions have similar clinical and histologic findings. The onset of oral lichenoid drug reactions appears to correspond to the administration of medications, especially antihypertensive drugs, oral hypoglycemic drugs, antimalarial drugs, gold salts, penicillamine and others. The author reports the case of 58-year-old male patient with oral lichenoid drug reaction, hypertension and diabetes mellitus. The oral manifestation showed radiated white lines with erythematous and erosive areas. The patient experienced pain and a burning sensation when eating spicy food. A tissue biopsy was carried out and revealed the characteristics of lichen planus. The patient was treated with 0.1% fluocinolone acetonide in an orabase as well as the replacement of the oral hypoglycemic and antihypertensive agents. The lesions improved and the burning sensation disappeared in two weeks after treatment. No recurrence was observed in the follow-up after three months. PMID:20120430

Kaomongkolgit, Ruchadaporn

2010-01-01

356

Drug watch.  

PubMed

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

Whitson, S

1999-01-01

357

Design and Feasibility of a Randomized Behavioral Intervention to Reduce Distributive Injection Risk and Improve HealthCare Access Among hepatitisC virus Positive Injection Drug Users: The Study to Reduce Intravenous Exposures (STRIVE)  

Microsoft Academic Search

Hepatitis C virus (HCV) is hyperendemic among injection drug users (IDUs). However, few scientifically proven interventions\\u000a to prevent secondary transmission of HCV from infected IDUs to others exist. This report describes the design, feasibility,\\u000a and baseline characteristics of participants enrolled in the Study to Reduce Intravenous Exposure (STRIVE). STRIVE was a multisite,\\u000a randomized-control trial to test a behavioral intervention developed

Farzana Kapadia; Mary H. Latka; Holly Hagan; Elizabeth T. Golub; Jennifer V. Campbell; Micaela H. Coady; Richard S. Garfein; David L. Thomas; Sebastian Bonner; Thelma Thiel; Steffanie A. Strathdee

2007-01-01

358

Genome analysis of multi- and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa.  

PubMed

The KZN strain family of Mycobacterium tuberculosis is a highly virulent strain endemic to the KwaZulu-Natal region of South Africa, which has recently experienced an outbreak of extensively-drug resistant tuberculosis. To investigate the causes and evolution of drug-resistance, we determined the DNA sequences of several clinical isolates--one drug-susceptible, one multi-drug resistant, and nine extensively drug-resistant--using whole-genome sequencing. Analysis of polymorphisms among the strains is consistent with the drug-susceptibility profiles, in that well-known mutations are observed that are correlated with resistance to isoniazid, rifampicin, kanamycin, ofloxacin, ethambutol, and pyrazinamide. However, the mutations responsible for rifampicin resistance in rpoB and pyrazinamide in pncA are in different nucleotide positions in the multi-drug-resistant and extensively drug-resistant strains, clearly showing that they acquired these mutations independently, and that the XDR strain could not have evolved directly from the MDR strain (though it could have arisen from another similar MDR strain). Sequencing of eight additional XDR strains from other areas of KwaZulu-Natal shows that they have identical drug resistant mutations to the first one sequenced, including the same polymorphisms at sites associated with drug resistance, supporting the theory that this represents a case of clonal expansion. PMID:19890396

Ioerger, Thomas R; Koo, Sunwoo; No, Eun-Gyu; Chen, Xiaohua; Larsen, Michelle H; Jacobs, William R; Pillay, Manormoney; Sturm, A Willem; Sacchettini, James C

2009-01-01

359

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

E-print Network

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

Gross, Louis J.

360

Psychophysiological prediction of choice: relevance to insight and drug addiction  

PubMed Central

An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400–1000 ms) and late (1000–2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker to help predict drug-related choice—and possibly associated behaviours (e.g. drug seeking in natural settings, relapse after treatment)—when insight (and self-report) is compromised. PMID:23148349

Moeller, Scott J.; Hajcak, Greg; Parvaz, Muhammad A.; Dunning, Jonathan P.; Volkow, Nora D.

2012-01-01

361

Regular Outpatient Medical and Drug Abuse Care and Subsequent Hospitalization of Persons Who Use Illicit Drugs  

Microsoft Academic Search

Results Hospitalization occurred in 55.6% of HIV-positive and 37.5% of HIV- negative drug users, with a mean of 27.5 and 24.5 inpatient days, respectively. In HIV- positive drug users, the adjusted odds ratio (AOR) for hospitalization was lowest among those with both regular medical and drug abuse care (AOR, 0.76; 95% confidence interval (CI), 0.67-0.85) followed by those with regular

Christine Laine; Walter W. Hauck; Marc N. Gourevitch; Jeffrey Rothman; Barbara J. Turner

2010-01-01

362

Offered: Offered: Position(s): Position(s)  

E-print Network

: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 are our top priority, and team members are our greatest asset! Computer Engineering, Computer Science a difference. This position requires the ability to work independently on projects with initial guidance from

New Hampshire, University of

363

Offered: Offered: Position(s): Position(s)  

E-print Network

profitability and identifying variances Experience ?General Accounting and Financial Analysis experience in this position is responsible for supporting the Finance group in the monthly closings, variance analysis, sales analysis and providing assistance to division Financial Analysts. ?Support Finance group in General

New Hampshire, University of

364

Changing Positions.  

ERIC Educational Resources Information Center

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

LaRose, Albert J.

1987-01-01

365

Some current studies of psychoactive and hallucinogenic drug use  

Microsoft Academic Search

Describes a study of a hippie subculture showing extensive, indiscriminant nonnarcotic drug use among hippies, and indifference to harmful drug effects. Among high-school students studied, alcohol and tobacco are still the most popular drugs, but marihuana, LSD, and psychoactive drugs are used by substantial numbers. Drug use relates to sex, grade level, and parental use of alcohol and tobacco. Social

Reginald G. Smart

1970-01-01

366

JAMA Patient Page: FDA Approval of New Drugs  

MedlinePLUS

... the drug might be toxic to cells). Animal testing: A drug that shows potential in laboratory test- ing may be tested on animals to investigate the drug’s safety (what side effects the drug may have) and provide information about ...

367

A Qualitative Examination of the Juvenile Drug Court Treatment Process  

Microsoft Academic Search

Drug treatment courts have proliferated at a remarkable rate, to over 1,000 drug court programs by May 2001. Literature has developed which shows drug courts to be generally effective for reducing recidivism and drug use. However, research on juvenile drug court treatment has lagged behind its adult predecessor. Recent research efforts emphasize the need to understand the process components of

Valerie Bryan; Matthew Hiller; Carl Leukefeld

2006-01-01

368

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

NASA Astrophysics Data System (ADS)

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

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

2014-07-01

369

Casimir experiments showing saturation effects  

SciTech Connect

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

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

2009-10-15

370

Compulsory licensing and access to drugs.  

PubMed

Compulsory licensing allows the use of a patented invention without the owner's consent, with the aim of improving access to essential drugs. The pharmaceutical sector argues that, if broadly used, it can be detrimental to innovation. We model the interaction between a company in the North that holds the patent for a certain drug and a government in the South that needs to purchase it. We show that both access to drugs and pharmaceutical innovation depend largely on the Southern country's ability to manufacture a generic version. If the manufacturing cost is too high, compulsory licensing is not exercised. As the cost decreases, it becomes a credible threat forcing prices down, but reducing both access and innovation. When the cost is low enough, the South produces its own generic version and access reaches its highest value, despite a reduction in innovation. The global welfare analysis shows that the overall impact of compulsory licensing can be positive, even when accounting for its impact on innovation. We also consider the interaction between compulsory licensing and the strength of intellectual property rights, which can have global repercussions in other markets beyond the South. PMID:24408475

Stavropoulou, Charitini; Valletti, Tommaso

2015-01-01

371

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

372

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2014 CFR

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

2014-04-01

373

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

374

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

375

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

PubMed Central

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

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

2013-01-01

376

DRUG NAME (INSERT DRUG NAME)  

Cancer.gov

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

377

Drug models of schizophrenia.  

PubMed

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

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

2015-02-01

378

Drug models of schizophrenia  

PubMed Central

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

Steeds, Hannah; Carhart-Harris, Robin L.

2015-01-01

379

The heart of Daphnia magna: effects of four cardioactive drugs.  

PubMed

We used Daphnia magna bioassays to determine the LC(50) and the effects on the heart of the cardioactive drugs ouabain, verapamil, metaproterenol and metoprolol. Distinctions were made between the pharmacological and toxicological effects of these drugs and the adequacy of physicochemical characteristics of its habitat (reconstituted water). Video microscopy and digital image processing were used to study the pharmacological effects on the heart. D. magna exhibited the expected sensitivity to the reference toxicant sodium dodecyl sulfate with a LC(50) of 15.6+/-4.5 mg/l. All drugs were toxic with 48 h-LC(50) of 2.03 mg/l ouabain, 7.04 mg/l verapamil, 32.45 mg/l metaproterenol and 76.21 mg/l metoprolol. Ouabain was the most toxic and caused a positive concentration-dependent inotropic effect. Verapamil caused positive chronotropic and inotropic effects, while metaproterenol showed positive concentration-dependent chronotropic effects at high concentrations (10(-3) and 10(-4) M). Metoprolol induced a positive chronotropic effect at low concentrations (10(-8), 10(-7), 10(-6) M) and a negative chronotropic effect at high concentration (10(-4) M). Ouabain, metaproterenol and metoprolol in D. magna caused similar effects to those produced in mammals. In contrast, verapamil caused opposite effects. The results suggest the presence of Na(+), K(+)-ATPase receptors to verapamil and of non-specific adrenergic receptors in heart of D. magna. PMID:14559294

Villegas-Navarro, Arturo; Rosas-L, Esperanza; Reyes, José L

2003-10-01

380

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

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

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

381

Drugs of abuse detection in saliva based on actuated optical method  

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

382

Drug Filtering  

NSDL National Science Digital Library

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

383

Transpapillary Drug Delivery to the Breast  

PubMed Central

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

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

2014-01-01

384

Positioning apparatus  

DOEpatents

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

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

1986-01-01

385

Positioning apparatus  

DOEpatents

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

Vogel, M.A.; Alter, P.

1983-07-07

386

Drug Usage Trends Among College Students  

ERIC Educational Resources Information Center

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

Girdano, Daniel A.; Girdano, Dorothy Dusek

1974-01-01

387

Generic vs. Branded Drugs for Parkinson's Disease  

MedlinePLUS

... vs. Branded Drugs for Parkinson’s Disease Text Size Generic vs. Branded Drugs for Parkinson’s Disease Currently, there are multiple pharmaceutical ... you should know that the FDA requires that generic drugs must show an “essential similarity” to the branded ...

388

[Tolerance and safety of drug arglabin].  

PubMed

The clinical researches were carried out on tolerance and safety of using an original medical drug Arglabin in capsules as immunomodulator. By results of researches the drug showed good tolerance and safety in healthy volunteers. Drug Arglabin in capsules as immunomodulator can be recommend for the further studying in the clinical practice. PMID:25617105

Tabriz, N; Skak, K; Mutaikhan, Z; Kozhamuratov, M; Serikbaeva, N

2014-12-01

389

Drugs and Alcohol: Their Relative Crash Risk  

PubMed Central

Objective: The purpose of this study was to determine (a) whether among sober (blood alcohol concentration [BAC] = .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; (b) whether among drinking (BAC > .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; and (c) whether alcohol and other drugs interact in increasing crash risk. Method: We compared BACs for the 2006, 2007, and 2008 crash cases drawn from the U.S. Fatality Analysis Reporting System (FARS) with control drug and blood alcohol data from participants in the 2007 U.S. National Roadside Survey. Only FARS drivers from states with drug information on 80% or more of the drivers who also participated in the 2007 National Roadside Survey were selected. Results: For both sober and drinking drivers, being positive for a drug was found to increase the risk of being fatally injured. When the drug-positive variable was separated into marijuana and other drugs, only the latter was found to contribute significantly to crash risk. In all cases, the contribution of drugs other than alcohol to crash risk was significantly lower than that produced by alcohol. Conclusions: Although overall, drugs contribute to crash risk regardless of the presence of alcohol, such a contribution is much lower than that by alcohol. The lower contribution of drugs other than alcohol to crash risk relative to that of alcohol suggests caution in focusing too much on drugged driving, potentially diverting scarce resources from curbing drunk driving. PMID:24411797

Romano, Eduardo; Torres-Saavedra, Pedro; Voas, Robert B.; Lacey, John H.

2014-01-01

390

Drugs Approved for Retinoblastoma  

Cancer.gov

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

391

Drug Coverage (Part D)  

MedlinePLUS

... insurance Find health & drug plans Drug coverage (Part D) How to get drug coverage Read about the ... through adding a Medicare Prescription Drug Plan (Part D), or getting a Medicare Advantage Plan (Part C) ...

392

Save on Drug Costs  

MedlinePLUS

... to lower your prescription drug costs Look into generic drugs. Ask your doctor if there are generics that ... to lower your prescription drug costs Look into generic drugs. Ask your doctor if there are generics that ...

393

Drugs Approved for Neuroblastoma  

Cancer.gov

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

394

Street Drugs and Pregnancy  

MedlinePLUS

... been added to your dashboard . Street drugs and pregnancy A street drug (also called illegal or illicit ... are abused How can street drugs harm your pregnancy? Using street drugs can cause problems for you ...

395

Drug abuse first aid  

MedlinePLUS

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

396

Drugs Approved for Leukemia  

Cancer.gov

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

397

Familiar drugs may prevent cancer  

Microsoft Academic Search

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

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

2001-01-01

398

Intelligence and Past Use of Recreational Drugs  

ERIC Educational Resources Information Center

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

Wilmoth, Daniel R.

2012-01-01

399

Marijuana and the Use of Other Drugs  

Microsoft Academic Search

IT is well established that the use of marijuana by young people is positively correlated with at least the experimental use of other drugs1. The probability that an individual uses the strong hallucinogens such as LSD and other drugs rises sharply with increasing frequency of marijuana use2. Such associations are not, of course, sufficient to establish causal relationships between the

William McGlothlin; Kay Jamison; Steven Rosenblatt

1970-01-01

400

[Drug Exposed Infants and Their Families.  

ERIC Educational Resources Information Center

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

Fenichel, Emily, Ed.

1992-01-01

401

Drug Education: The Challenge to Teacher Preparation.  

ERIC Educational Resources Information Center

The author offers a brief description of the Southern Regional Education Board (SREB) drug education project and develops the position taken by this project. Emphasis is placed on the schools' responsibility for helping eliminate drug abuse and for the implementation of an affective curriculum to achieve this goal. The curriculum focuses on such…

Wiggins, Xenia R.

402

Educational Outreach: The Space Science Road Show  

NASA Astrophysics Data System (ADS)

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

Cox, N. L. J.

2002-01-01

403

Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions  

PubMed Central

Background Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers. Methods We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling. Results Of the 5 × 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses. Conclusion We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases. PMID:24101737

Schmidt, Linnéa; Kling, Teresia; Monsefi, Naser; Olsson, Maja; Hansson, Caroline; Baskaran, Sathishkumar; Lundgren, Bo; Martens, Ulf; Häggblad, Maria; Westermark, Bengt; Forsberg Nilsson, Karin; Uhrbom, Lene; Karlsson-Lindahl, Linda; Gerlee, Philip; Nelander, Sven

2013-01-01

404

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province.  

PubMed

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive (ss+ and/or c+) two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination. Questionnaire was carried out to collect data on treatment history, demographics and possible risk factors. Chi-square test and logistic regression were conducted using SPSS in this study. As the result, 99 active TB patients were identified and the recurrence rate was 16.67% and irregular medicine and smoking were the causes of the recurrence. The retreatment TB patients with sputum smear and/or culture positive in this study had higher recurrence rate and health education work on regular medication and smoking should be strengthened. PMID:25716568

Li, Fang; Song, Chun Yan; Zhao, Fei; Liang, Ming Li; Liu, Zhi Min; Guo, Xiao Yan; Wang, Yu; He, Guang Xue

2015-02-01

405

Therapeutic drug monitoring of psychotropic drugs. TDM "nouveau".  

PubMed

TDM applied in psychiatry dates back several decades. The reason for this is that, after the advent of modern clinical psychopharmacology around the middle of the past century, an insight came to common knowledge about the existence of (1) a large interindividual pharmacokinetic (PK) variability for virtually all psychoactive drugs and (2) a worse clinical efficacy not only in inadequate drug concentrations but also in excessively high concentrations. From this concept, the definition of a therapeutic concentration "window" was evidenced for a substantial number of, primarily, antidepressant drugs. However, with the further extensive development of the clinically available pharmacopoeia of psychoactive drugs from the later 1980s until today, the concept of less toxic compounds than before has commonly been launched in the marketing strategies for these newer drugs. This concept also led to the idea that TDM was no longer necessary for the newer types of psychoactive drugs, a position backed up by difficulties in unraveling concentration-effect relationships generally for these drugs in clinical trials. The present survey summarizes the background history for TDM in psychiatry and makes a critical appraisal of why a "lack" of definition of concentration-effect relationships for newer psychoactive drugs is now common. This survey also provides the reader with a novel concept challenging ambient TDM strategies (referred to as TDM "traditionelle") in psychiatry by forwarding a theoretical model called TDM "nouveau." In this model both inter- and intraindividual (over time) PK variation is suggested to be used for dose optimization by TDM in a naturalistic clinical setting. The previous concept of a simple, common concentration "window" existing for all such drugs is questioned by promotion of the use of available PK data merely as "guiding principles" rather than as "reference values" when interpreting the TDM outcome in individual cases. PMID:15228155

Bengtsson, Finn

2004-04-01

406

Antiplatelet Drugs  

PubMed Central

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

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

2012-01-01

407

Impact of Psychotropic Drugs on QT Interval Dispersion in Adult Patients  

PubMed Central

Background Drug-induced increase in QT dispersion has been associated with potentially fatal ventricular arrhythmias. Little is known about the use of psychotropic substances, alone or in combination with other drugs on QT dispersion. Objectives To evaluate the impact of psychotropic drugs on QT interval dispersion in adults. Methods An observational cohort study was designed involving 161 patients hospitalized from an emergency department at a tertiary hospital, divided into psychotropic users or non-users. Demographic, clinical, laboratory data and drugs used on a regular basis were collected on admission, in addition to 12-lead electrocardiogram with QT dispersion measurement. Results QT dispersion was significantly higher in the psychotropic user group compared to non-users (69.25 ± 25.5 ms vs. 57.08 ± 23.4 ms; p = 0.002). The QT interval corrected by Bazzett formula was also higher in the psychotropic drugs user group, with statistical significance. (439.79 ± 31.14 ms vs. 427.71 ± 28.42 ms; p = 0.011). A regression analysis model showed a positive association between the number of psychotropic drugs used and QT interval dispersion, with r = 0.341 and p < 0.001. Conclusions The use of psychotropic drugs was associated with increased QT dispersion and this increase was accentuated, as the number of psychotropic drugs used was higher. PMID:24830389

Claudio, Bruno de Queiroz; Costa, Marcelle Azevedo Nossar; Penna, Filipe; Konder, Mariana Teixeira; Celoria, Bruno Miguel Jorge; de Souza, Luciana Lopes; Pozzan, Roberto; Schneider, Roberta Siuffo; Albuquerque, Felipe Neves; Albuquerque, Denilson Campos

2014-01-01

408

Automatic construction of a large-scale and accurate drug-side-effect association knowledge base from biomedical literature.  

PubMed

Systems approaches to studying drug-side-effect (drug-SE) associations are emerging as an active research area for drug target discovery, drug repositioning, and drug toxicity prediction. However, currently available drug-SE association databases are far from being complete. Herein, in an effort to increase the data completeness of current drug-SE relationship resources, we present an automatic learning approach to accurately extract drug-SE pairs from the vast amount of published biomedical literature, a rich knowledge source of side effect information for commercial, experimental, and even failed drugs. For the text corpus, we used 119,085,682 MEDLINE sentences and their parse trees. We used known drug-SE associations derived from US Food and Drug Administration (FDA) drug labels as prior knowledge to find relevant sentences and parse trees. We extracted syntactic patterns associated with drug-SE pairs from the resulting set of parse trees. We developed pattern-ranking algorithms to prioritize drug-SE-specific patterns. We then selected a set of patterns with both high precisions and recalls in order to extract drug-SE pairs from the entire MEDLINE. In total, we extracted 38,871 drug-SE pairs from MEDLINE using the learned patterns, the majority of which have not been captured in FDA drug labels to date. On average, our knowledge-driven pattern-learning approach in extracting drug-SE pairs from MEDLINE has achieved a precision of 0.833, a recall of 0.407, and an F1 of 0.545. We compared our approach to a support vector machine (SVM)-based machine learning and a co-occurrence statistics-based approach. We show that the pattern-learning approach is largely complementary to the SVM- and co-occurrence-based approaches with significantly higher precision and F1 but lower recall. We demonstrated by correlation analysis that the extracted drug side effects correlate positively with both drug targets, metabolism, and indications. PMID:24928448

Xu, Rong; Wang, QuanQiu

2014-10-01

409

[Myonecrosis in users of injecting drugs (a clinical case)].  

PubMed

Myonecrosis remains one of the severest manifestations of skin and soft tissue infections. Clostridia (C. perfringens, C. novyi, C. septicum, C. sordellii, C. histolyticum) are dominant and Staphylococcus aureus, Streptococcus pyogenes, Bacillus cereus, and Bacteriodes fragilis are much less in the etiology of myonecrosis. Cases of gas gangrene have recently become more frequent among injection drug users all over the world. Russia has become the largest opiate market in Europe and consumption of these narcotic drugs is annually growing. In the Russian Federation, a larger number of injection drug users uniquely results in a rise of cases of Clostridium- and mixed flora-induced myonecrosis. Gas gangrene in HIV-positive drug abusers seems to rapidly progress to multiple organ failure and to show high death rates, rather than to develop a localized form. The analyzed case of mixed flora-induced gas gangrene is of interest to physicians of any specialties who can encounter this wound infection in HIV-positive patients. PMID:21381347

Shestakova, I V; Iushchuk, N D; Tishkevich, O L

2010-01-01

410

[Treatment of overactive bladder in older women increased doses of antimuscarinic drugs safe and effective alternative to existing methods].  

PubMed

The study included 95 female patients of 65 to 74 years (average age 67,1 years), who previously (more than 6 months before this study) took a course of monotherapy with hydrochloride trospium in higher dosages with unstable or weak effect. In this study, all patients were divided into three groups and were treated with two antimuscarinic drugs. The majority of older women suffering from OAB and treatment-resistant taking one antimuscarinic drug in high doses showed a significant positive progress in a state by adding a second antimuscarinic agent. The received side effects do not exceed thereof in comparison with treatment with a single drug. PMID:25051773

Kosilov, K V; Loparev, S A; Krasnykh, M A; Kosilova, L V

2014-01-01

411

Evolutionary inspirations for drug discovery.  

PubMed

Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs. PMID:20724009

Zhang, Hong-Yu; Chen, Ling-Ling; Li, Xue-Juan; Zhang, Jian

2010-10-01

412

Atomic level rendering of DNA-drug encounter.  

PubMed

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

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

2014-01-21

413

Atomic Level Rendering of DNA-Drug Encounter  

PubMed Central

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

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

2014-01-01

414

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

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

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

415

10. VIEW FROM ABOVE SHOWING TRACK WITH BRIDGE IN OPEN ...  

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

10. VIEW FROM ABOVE SHOWING TRACK WITH BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Groton Bridge, Spanning Thames River between New London & Groton, New London, New London County, CT

416

8. VIEW LOOKING EAST, SHOWING COUNTERWEIGHT WITH BRIDGE IN OPEN ...  

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

8. VIEW LOOKING EAST, SHOWING COUNTERWEIGHT WITH BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Groton Bridge, Spanning Thames River between New London & Groton, New London, New London County, CT

417

9. VIEW, LOOKING EAST, SHOWING TRACK WITH BRIDGE IN OPEN ...  

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

9. VIEW, LOOKING EAST, SHOWING TRACK WITH BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Groton Bridge, Spanning Thames River between New London & Groton, New London, New London County, CT

418

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

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

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

419

Positioning and Position Error of Petroleum Wells  

NASA Astrophysics Data System (ADS)

We present a new model for the estimation of positional uncertainty of petroleum wells. The model uses a heavy tailed normal inverse Gaussian distribution for the errors in Earth's magnetic field reference values. These references are required for calculating the position of a well using magnetic directional surveying. The results show that the normal inverse Gaussian distribution gives a more realistic fit to the Earth's magnetic field reference values than the normal distribution, which is the current state of art. Errors in surveying sensors and reference errors are propagated along the well path to obtain the positioning uncertainty. The positional uncertainty is important for the probability of collisions between wells and for drilling accurate relief wells when an eventual collision has resulted in a blow-out situation. We compare results of the normal model used in the petroleum industry with our proposed model. The comparison is made for anti-collision calculations between drilled wells and a planned well. The results indicate a higher risk of collisions for certain well geometries when using the normal distribution, while a collision is avoided in the normal inverse Gaussian situation. We find clear differences between an approximate normal test and a Monte Carlo test.

Gjerde, Tony; Eidsvik, Jo; Nyrnes, Erik; Bruun, Bjørn

2011-01-01

420

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

USGS Publications Warehouse

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

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

2014-01-01

421

Nanostructured amphiphilic star-hyperbranched block copolymers for drug delivery.  

PubMed

A robust drug delivery system based on nanosized amphiphilic star-hyperbranched block copolymer, namely, poly(methyl methacrylate-block-poly(hydroxylethyl methacrylate) (PMMA-b-PHEMA) is described. PMMA-b-PHEMA was prepared by sequential visible light induced self-condensing vinyl polymerization (SCVP) and conventional vinyl polymerization. All of the synthesis and characterization details of the conjugates are reported. To accomplish tumor cell targeting property, initially cell-targeting (arginylglycylaspactic acid; RGD) and penetrating peptides (Cys-TAT) were binding to each other via the well-known EDC/NHS chemistry. Then, the resulting peptide was further incorporated to the surface of the amphiphilic hyperbranched copolymer via a coupling reaction between the thiol (-SH) group of the peptide and the hydroxyl group of copolymer by using N-(p-maleinimidophenyl) isocyanate as a heterolinker. The drug release property and targeting effect of the anticancer drug (doxorobucin; DOX) loaded nanostructures to two different cell lines were evaluated in vitro. U87 and MCF-7 were chosen as integrin ?v?3 receptor positive and negative cells for the comparison of the targeting efficiency, respectively. The data showed that drug-loaded copolymers exhibited enhanced cell inhibition toward U87 cells in compared to MCF-7 cells because targeting increased the cytotoxicity of drug-loaded copolymers against integrin ?v?3 receptor expressing tumor cells. PMID:25816726

Seleci, Muharrem; Seleci, Didem Ag; Ciftci, Mustafa; Odaci Demirkol, Dilek; Stahl, Frank; Timur, Suna; Scheper, Thomas; Yagci, Yusuf

2015-04-21

422

Intracochlear Drug Delivery Systems  

PubMed Central

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

Borenstein, Jeffrey T.

2011-01-01

423

[Resistance to antituberculous drugs].  

PubMed

Mycobacteria responsible for tuberculosis (M. tuberculosis, M. bovis, M. africanum) are susceptible to a very small number of antibiotics. As soon as these drugs were used in humans all gave rise to the selection of resistant mycobacteria. Study of the mechanisms of acquired resistance, with the help of the genetics of mycobacteria, led to a more accurate understanding of the mode of action of antituberculous drugs. The antibiotics isoniazid, pyrazinamide, ethionamide and ethambutol are mycobacteria-specific because they inhibit the synthesis of mycolic acids, which are specific constituants of the bacterial wall. Mutations responsible for resistance to these drugs affect genes coding for activator enzymes (katg for isoniazid, pncA for pyrazinamide) or genes coding for their target (inhA for isoniazid/ethionamide, embB for ethambutol). With rifamycins, aminosides and quinolones, mechanisms of action and resistance are the same for mycobacteria as for non-mycobacterial organisms. No plasmid or resistance transposon has been described in M. tuberculosis. Currently a test for the quick detection of resistance to rifampicin is widely available but in the future DNA chips may allow the simultaneous detection of multiple resistances. Monitoring of antituberculous drugs shows that in France the prevalence of multiresistance ( resistance to both isoniazid and rifampicin) is 0.5%, primary resistance (before treatment) is 9%, and secondary resistance (after treatment) is 16%. PMID:16129320

Veziris, N; Cambau, E; Sougakoff, W; Robert, J; Jarlier, V

2005-08-01

424

Construction of Drug Network Based on Side Effects and Its Application for Drug Repositioning  

PubMed Central

Drugs with similar side-effect profiles may share similar therapeutic properties through related mechanisms of action. In this study, a drug-drug network was constructed based on the similarities between their clinical side effects. The indications of a drug may be inferred by the enriched FDA-approved functions of its neighbouring drugs in the network. We systematically screened new indications for 1234 drugs with more than 2 network neighbours, 36.87% of the drugs achieved a performance score of Normalized Discounted Cumulative Gain in the top 5 positions (NDCG@5)?0.7, which means most of the known FDA-approved indications were well predicted at the top 5 positions. In particular, drugs for diabetes, obesity, laxatives and antimycobacterials had extremely high performance with more than 80% of them achieving NDCG@5?0.7. Additionally, by manually checking the predicted 1858 drug-indication pairs with Expression Analysis Systematic Explorer (EASE) score?10?5 (EASE score is a rigorously modified Fisher exact test p value), we found that 80.73% of such pairs could be verified by preclinical/clinical studies or scientific literature. Furthermore, our method could be extended to predict drugs not covered in the network. We took 98 external drugs not covered in the network as the test sample set. Based on our similarity criteria using side effects, we identified 41 drugs with significant similarities to other drugs in the network. Among them, 36.59% of the drugs achieved NDCG@5?0.7. In all of the 106 drug-indication pairs with an EASE score?0.05, 50.94% of them are supported by FDA approval or preclinical/clinical studies. In summary, our method which is based on the indications enriched by network neighbors may provide new clues for drug repositioning using side effects. PMID:24505324

Ye, Hao; Liu, Qi; Wei, Jia

2014-01-01

425

[Drug induced eosinophilic pleural effusion].  

PubMed

The hypersensitivity reactions induced by drugs, some widely used, like central nervous system medication, can have various presentations. The lung is a frequent target for such events. We present the case of 40-year-old male patient, non-smoker, with infant encephalopaty, seizures since age of 6 with polimorphic crisis (mainly absences), with anticonvulsivant treatment since 2011 (carbamazepine, sodium valproate, levetiracetam), with no respiratory medical history. Current symptoms started two weeks before, with chest pain, dry cough. He received no antibiotics. Chest X-ray and thoracic CT scan (27 June 2013) showed a left pleral effusion. Left exploratory thoracocentesis extracted 20 ml reddish pleural fluid: eosinophilic exsudate (60%) with normal adenosin deaminase. He also presents moderate blood eosinophilia (13.7%-1780/mm3). Pulmonary infarction with secondary pleurisy, thoracic trauma, acute pancreatitis with secondary pleurisy were excluded. No Loeffler transient infiltrates were documented, serology for Toxocara is IgG positive (historical) and not significant for current episode, no symptoms suggestive for toxocarosis (characteristic to young children, patient had no liver enlargement etc.), no hidatidosis or trichinelosis were found. As an exclusion diagnosis, a hypersensitivity reaction to anticonvulsivant medication was considered (mentioned in literature) carbamazepine and sodium valproate (even if medication was taken for a longer time), with blood and pleural eosinophilia. Together with the neurologist, the mentioned drugs were stopped and he was started on lamotrigine 2 tb/day and levetiracetam 1 tb/day, well tolerated, no absences were noticed. Total remission of blood eosinophilia and partial remission of pleural effusion were noticed. Subsequent follow-ups confirm favourable evolution, with healing of pleurisy and normal blood cell count, which are stable at 7 months after changing anticonvulsivant treatment. PMID:25241560

Vasilescu, Raluca

2014-01-01

426

Transpapillary drug delivery to the breast.  

PubMed

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

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

2014-01-01

427

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery  

NASA Astrophysics Data System (ADS)

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

Ensign-Hodges, Laura

428

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

NASA Astrophysics Data System (ADS)

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

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

429

Drug resistance of Mycobacterium tuberculosis isolated from treated patients in Pakistan.  

PubMed

An investigation was carried out to establish the extent of drug resistance among treated patients. A sample population of patients living in Lahore, Pakistan, which is a high prevalence area for tuberculosis, was studied. The total of 256 culture-positive cases in this study were divided into three groups according to the length of previous treatment. There was no significant difference in the antituberculosis treatment regimens or the drug resistance pattern among the three groups. All the patients had had at least three drugs for more than 6 months, and streptomycin and isoniazid were always included in the regimen. About one-third of the patients showed resistance to one or more drug, with the highest resistance being to streptomycin and INH. Resistance to rifampicin, which was introduced fairly recently in this area, was a little more than 5%, which is an increase from the last report. PMID:2476880

Aziz, A; Siddiqi, S H; Aziz, K; Ishaq, M

1989-03-01

430

Examining the Effects of Mass Media Campaign Exposure and Interpersonal Discussions on Youth's Drug Use: The Mediating Role of Visiting ProDrug Websites  

Microsoft Academic Search

To extend past research on interpersonal communication and campaign effects, we hypothesized that anti-drug mass media campaign message exposure indirectly affects visiting anti- and pro-drug websites through targeted parent–child and friend-to-friend communication against drugs, as well as through having drug-related discussions during organized group activities. Second, we posited that engaging in anti-drug interpersonal communication indirectly affects adolescents' drug use through

Jennifer A. Kam; Chul-joo Lee

2012-01-01

431

Drug Use among Iranian Drivers Involved in Fatal Car Accidents  

PubMed Central

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

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

2014-01-01

432

Personality, Drug Preference, Drug Use, and Drug Availability  

ERIC Educational Resources Information Center

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

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

2011-01-01

433

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

PubMed Central

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

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

2015-01-01

434

The impact of trauma on drug users’ identities  

Microsoft Academic Search

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

Kim Etherington

2007-01-01

435

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

ERIC Educational Resources Information Center

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

Page, Richard C.

1983-01-01

436

One Dimensional Motion: Position versus Time Graphs  

NSDL National Science Digital Library

In the following exercises, the graph drawn is of position versus time. The animation shows the position of a puck as time progresses. Note the position of the puck at various times and compare the animation to the graph.

Wolfgang Christian

437

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

PubMed Central

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

2014-01-01

438

Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus.  

PubMed

This study was conducted to evaluate time-dependent pharmacokinetic changes and drug interactions over the first 6 months after transplantation in kidney transplant recipients receiving tacrolimus (TAC), prednisone (PRED) and mycophenolate mofetil (MMF) or sirolimus (SRL). Pharmacokinetic assessments were carried out at day 7 and months 1, 3, and 6 in kidney transplant recipients receiving TAC plus PRED with either MMF (2 g/day, n = 13) or SRL (15 mg loading dose, 5 mg for 7 days followed by 2 mg/day, n = 12). There were no differences in the main demographic characteristics or in mean PRED doses during the first 6 months after transplant. From day 7 to month 6, there was a 65% increase in TAC dose corrected exposure (dose corrected area under the curve; AUC) in patients receiving MMF (P = 0.005) and a 59% increase in TAC dose corrected exposure in patients receiving SRL (P = 0.008). From day 7 to month 6, there was a 72% increase in mycophenolate dose corrected exposure (P = 0.001) and a 65% increase in SRL dose corrected exposure (P = 0.008). TAC dose corrected exposure was 23% lower in patients receiving SRL compared with MMF (P = 0.012) on average over the study period. PRED dose reduction was associated with increase in TAC (in patients receiving SRL, P = 0.040) and mycophenolic acid (MPA) (P = 0.070) drug exposures. Tercile distribution of TAC drug exposure showed a positive correlation with mean SRL exposures (P = 0.016). Conversely, tercile distribution of SRL drug exposure showed a positive correlation with mean TAC exposures (P = 0.004). Time-dependent increases in TAC, MPA and SRL drug exposures occur up to 6 months after transplantation. Drug-to-drug interactions indicate that intense therapeutic drug monitoring is required to avoid under- or over-immunosuppression. PMID:19267777

Park, Sung-In; Felipe, Claudia R; Pinheiro-Machado, Paula G; Garcia, Riberto; Fernandes, Fernanda B; Casarini, Dulce E; Tedesco-Silva, Helio; Medina-Pestana, Jose O

2009-02-01

439

Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics  

PubMed Central

Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

2014-01-01

440

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

PubMed

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

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

2015-03-18

441

99 Films on Drugs.  

ERIC Educational Resources Information Center

This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

Weber, David O., Ed.

442

Drugs Approved for Cervical Cancer  

MedlinePLUS

Other Drug Resources A to Z List of Cancer Drugs Drugs Approved for Different Types of Cancer Drugs Approved ... NCI Dictionary of Cancer Terms NCI Drug Dictionary Drugs Approved for Cervical Cancer This page lists cancer ...