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Sample records for drug shows positive

  1. Experimental Drug for Rheumatoid Arthritis Shows Promise

    MedlinePlus

    ... medlineplus/news/fullstory_158076.html Experimental Drug for Rheumatoid Arthritis Shows Promise Baricitinib helped patients who failed other ... 2016 (HealthDay News) -- An experimental drug to treat rheumatoid arthritis showed promise in a new six-month trial. ...

  2. New Drug Shows Promise Against Severe Sinusitis

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_157064.html New Drug Shows Promise Against Severe Sinusitis In early ... more severe patients are the target of the new treatment option," explained study author Dr. Claus Bachert, ...

  3. Cuba shows jump in HIV positives.

    PubMed

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

  4. Family Checkup: Positive Parenting Prevents Drug Abuse

    MedlinePlus

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

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

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

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

  6. 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 (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

  8. 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

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

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

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

  10. 17. DETAIL VIEW OF ROLLER GATE (IN RAISED POSITION), SHOWING ...

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

    17. DETAIL VIEW OF ROLLER GATE (IN RAISED POSITION), SHOWING GATE FLANGES, GATE HEATER (LEFT FOREGROUND), ROLLER TRACK, CHAIN AND BRIDGE GIRDER, LOOKING EAST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 3, Red Wing, Goodhue County, MN

  11. 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

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

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

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

  13. 19. VIEW, LOOKING SOUTHWEST, SHOWING BRIDGE IN CLOSED POSITION ...

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

    19. VIEW, LOOKING SOUTHWEST, SHOWING BRIDGE IN CLOSED POSITION - New York, New Haven & Hartford Railroad, Niantic Bridge, Spanning Niantic River between East Lyme & Waterford, Old Lyme, New London County, CT

  14. Drug Shows Promise Against Rare, Aggressive Skin Cancer

    MedlinePlus

    ... fullstory_158389.html Drug Shows Promise Against Rare, Aggressive Skin Cancer Research suggests IV med might benefit ... tumor cells may help people with a rare, aggressive form of skin cancer, a preliminary study suggests. ...

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

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

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

  16. Experimental Lung Cancer Drug Shows Early Promise | Poster

    Cancer.gov

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

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

    PubMed Central

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

    2015-01-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca2+, and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. PMID:26195527

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

    PubMed

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

    2015-10-01

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

  19. Family Checkup: Positive Parenting Prevents Drug Abuse

    MedlinePlus

    ... Abuse Could your kids be at risk for substance abuse? Families strive to find the best ways to ... drugs. Research supported by the National Institute on Drug Abuse (NIDA) has shown the important role that parents ...

  20. Neurotensin-deficient mice show altered responses to antipsychotic drugs

    PubMed Central

    Dobner, Paul R.; Fadel, Jim; Deitemeyer, Nancy; Carraway, Robert E.; Deutch, Ariel Y.

    2001-01-01

    The peptide transmitter neurotensin (NT) exerts diverse neurochemical effects that resemble those seen after acute administration of antipsychotic drugs (APDs). These drugs also induce NT expression in the striatum; this and other convergent findings have led to the suggestion that NT may mediate some APD effects. Here, we demonstrate that the ability of the typical APD haloperidol to induce Fos expression in the dorsolateral striatum is markedly attenuated in NT-null mutant mice. The induction of Fos and NT in the dorsolateral striatum in response to typical, but not atypical, APDs has led to the hypothesis that the increased expression of these proteins is mechanistically related to the production of extrapyramidal side effects (EPS). However, we found that catalepsy, which is thought to reflect the EPS of typical APDs, is unaffected in NT-null mutant mice, suggesting that NT does not contribute to the generation of EPS. We conclude that NT is required for haloperidol-elicited activation of a specific population of striatal neurons but not haloperidol-induced catalepsy. These results are consistent with the hypothesis that endogenous NT mediates a specific subset of APD actions. PMID:11427716

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Positive drug test results; procedures. 219.605 Section 219.605 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug...

  2. 49 CFR 219.605 - Positive drug test results; procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Positive drug test results; procedures. 219.605 Section 219.605 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug...

  3. 49 CFR 219.605 - Positive drug test results; procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Positive drug test results; procedures. 219.605 Section 219.605 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug...

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

    PubMed Central

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

    2012-01-01

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

  5. One-a-Day Anti-Seizure Drug Shows Promise for People with Epilepsy

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158318.html One-a-Day Anti-Seizure Drug Shows Promise for People With ... report. Their preliminary study compared the once-a-day drug eslicarbazepine acetate (Aptiom) to the twice-daily ...

  6. Camera position east of CO172CE6, showing more of north and ...

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

    Camera position east of CO-172-CE-6, showing more of north and east sides of middle east wing. - Fitzsimons General Hospital, Laundry, Southeast corner of East Harlow Avenue & South Twelfth Street, Aurora, Adams County, CO

  7. Camera position east of CO172CE8, showing east sides of two ...

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

    Camera position east of CO-172-CE-8, showing east sides of two most eastern wings and north side of most eastern wing. - Fitzsimons General Hospital, Laundry, Southeast corner of East Harlow Avenue & South Twelfth Street, Aurora, Adams County, CO

  8. Positive urgency predicts illegal drug use and risky sexual behavior.

    PubMed

    Zapolski, Tamika C B; Cyders, Melissa A; Smith, Gregory T

    2009-06-01

    There are several different personality traits that dispose individuals to engage in rash action. One such trait is positive urgency: the tendency to act rashly when experiencing extremely positive affect. This trait may be relevant for college student risky behavior, because it appears that a great deal of college student risky behavior is undertaken during periods of intensely positive mood states. To test this possibility, the authors conducted a longitudinal study designed to predict increases in risky sexual behavior and illegal drug use over the course of the first year of college (n=407). In a well-fitting structural model, positive urgency predicted increases in illegal drug use and risky sexual behavior, even after controlling for time 1 (T1) involvement in both risky behaviors, biological sex, and T1 scores on four other personality dispositions to rash action. The authors discuss the theoretical and practical implications of this finding. PMID:19586152

  9. Positive Urgency Predicts Illegal Drug Use and Risky Sexual Behavior

    PubMed Central

    Zapolski, Tamika C. B.; Cyders, Melissa A.; Smith, Gregory T.

    2009-01-01

    There are several different personality traits that dispose individuals to engage in rash action. One such trait is positive urgency: the tendency to act rashly when experiencing extremely positive affect. This trait may be relevant for college student risky behavior, because it appears that a great deal of college student risky behavior is undertaken during periods of intensely positive mood states. To test this possibility, the authors conducted a longitudinal study designed to predict increases in risky sexual behavior and illegal drug use over the course of the first year of college (n = 407). In a well-fitting structural model, positive urgency predicted increases in illegal drug use and risky sexual behavior, even after controlling for time 1 (T1) involvement in both risky behaviors, biological sex, and T1 scores on four other personality dispositions to rash action. The authors discuss the theoretical and practical implications of this finding. PMID:19586152

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

    MedlinePlus

    ... System Shows Early Promise for Treating Lupus in Mice A drug delivery system using nanoparticle technology that ... administered the MPA-loaded nanogel to lupus-prone mice that had not yet developed symptoms of the ...

  11. New Drug for Severe Form of Arthritis Shows Promise in Trial

    MedlinePlus

    ... Shows Promise in Trial Already approved to treat psoriasis, higher dose of Cosentyx helped 60 percent of ... A drug recently approved for the skin condition psoriasis may also help people with a debilitating form ...

  12. Camera position east of CO172CE7, showing north and east sides ...

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

    Camera position east of CO-172-CE-7, showing north and east sides of the two most eastern wings. Note three wall anchors on north side of most eastern wing. - Fitzsimons General Hospital, Laundry, Southeast corner of East Harlow Avenue & South Twelfth Street, Aurora, Adams County, CO

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

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

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

  14. Consequences of a false-positive mammography result: drug consumption before and after screening.

    PubMed

    von Euler-Chelpin, My; Bæksted, Christina; Vejborg, Ilse; Lynge, Elsebeth

    2016-05-01

    Background Previous research showed women experiencing false-positive mammograms to have greater anxiety about breast cancer than women with normal mammograms. To elucidate psychological effects of false-positive mammograms, we studied impact on drug intake. Methods We calculated the ratio of drug use for women with false-positive versus women with normal mammograms, before and after the event, using population-based registers, 1997-2006. The ratio of the ratios (RRR) assessed the impact. Results Before the test, 40.3% of women from the false-positive group versus 36.2% from the normal group used anxiolytic and antidepressant drugs. There was no difference in use of beta blockers. Hormone therapy was used more frequently by the false-positive, 36.6% versus 28.7%. The proportion of women using anxiolytic and antidepressant drugs increased with 19% from the before to the after period in the false-positive group, and with 16% in the normal group, resulting in an RRR of 1.02 (95% CI 0.92-1.14). RRR was 1.03 for beta blockers, 0.97 for hormone therapy. Conclusion(s) Drugs used to mitigate mood disorders were used more frequently by women with false-positive than by women with normal mammograms already before the screening event, while the changes from before to after screening were similar for both groups. The results point to the importance of control for potential selection in studies of screening effects. PMID:26799406

  15. Observational and Clinical Trial Findings on the Comparative Effectiveness of Diabetes Drugs Showed Agreement

    PubMed Central

    Flory, James H; Mushlin, Alvin I

    2014-01-01

    Objective This study compares an observational study of diabetes treatment effectiveness to randomized controlled trials to assess their convergent validity. Study Design and Setting Multivariable models were developed using observational data to describe change in HbA1c (% unit) and weight (kilograms) after addition of a second-line oral diabetes drug to metformin monotherapy. Randomized trials of these scenarios were systematically identified. The models were used to simulate each trial, and simulated and actual results were compared by linear regression and meta-analysis. Results 32 randomized trials of second-line diabetes oral therapy were identified. For all outcomes and drugs studied, simulation and actual results correlated (p < 0.001). There were no statistically significant differences between meta-analyzed randomized and simulated results for effect on HbA1c. For effect on weight, results were qualitatively comparable, but for sulfonylureas the simulated weight gain was nominally greater than seen in the randomized controlled trials. Conclusions An observational study of diabetes drug effectiveness showed convergent validity with randomized data. This supports cautious use of the observational research to draw conclusions about drug effectiveness in populations not studied in clinical trials. This approach may be useful in other situations where observational and randomized data need integration. PMID:25432086

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

    PubMed

    Moriya, Fumio

    2009-04-01

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

  17. [A Case of Brainstem Cavernous Hemangioma Showing False Positive Response to Electromyographic Tracheal Tube].

    PubMed

    Kadoya, Tatsuo; Yamamoto, Toshinori; Uehara, Hirofumi; Kinoshita, Yuki; Shiraishi, Munehiro; Joyashiki, Takeshi; Watake, Tomoko; Enokida, Kengo

    2015-08-01

    Brainstem cavernous hemangioma is a complex lesion associated with hemorrhage and neurological deficit. The damage of the vagus nerve is a devastating surgical complication. Therefore, intraoperative anatomical and functional evaluation of this nerve is crucial. We used electromyographic tracheal tube (EMG tube)to monitor electromyogram from the vocal cord. We report a case of brainstem cavernous hemangioma showing false positive response to EMG tube. A 66-year-old woman underwent resection of cavernous hemangioma in the pontine tegmentum. General anesthesia was induced with remifentanl, propofol, and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord, orbicularis oculi, orbicularis oris and lateral rectus. When the manipulation reached brainstem, slight spontaneous respiration (SR) appeared on capnogram. Simultaneously, an alarm rang. Exposed nerves were stimulated electrically. However, there was no electromyographic response on the vocal cord. We concluded that the cause was SR accompanied by vocal cord movement. Remifentanil was increased up to 1 μg x kg(-1) x min(-1). SR did not disappear. Remifentanil was not increased any more without hindering the operation. Her operative course was uneventful. It is necessary to pay attention to false positive response caused by SR with EMG tube. PMID:26442411

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

    PubMed

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

    2013-05-01

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

  19. FOXP2 Targets Show Evidence of Positive Selection in European Populations

    PubMed Central

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

    2013-01-01

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

  20. Mirtazapine as positive control drug in studies examining the effects of antidepressants on driving ability.

    PubMed

    Verster, Joris C; van de Loo, Aurora J A E; Roth, Thomas

    2015-04-15

    The development of effective and safe antidepressant medications is ongoing, and driving studies are critical to assess a drug's safety. The current review summarizes the effects of a sedating effective antidepressant, mirtazapine, on driving ability, and its potential to serve as positive control drug in future driving studies. Three on-road driving studies and four driving simulator studies of mirtazapine were identified. The studies, conducted in healthy volunteers, showed a significant dose-dependent driving impairment, the first day following bedtime administration of mirtazapine. The magnitude of impairment after a single dose of 15 mg or 30 mg mirtazapine was comparable to that observed with a blood alcohol concentration of 0.05%, the legal limit for driving in many countries. After 1 or 2 weeks of daily treatment with mirtazapine, partial tolerance developed to mirtazapine's effects on driving. Driving studies conducted in patients were less informative, as the effect on driving caused by mirtazapine was obscured by a drug-disease interaction and increased variability in patient groups. In conclusion, mirtazapine is useful as positive control drug to assess the potential effects of new antidepressant drugs on driving. Studies in normal healthy volunteers are more sensitive to drug effects than studies in patient populations. PMID:25446559

  1. HIV-specific changes in the motor performance of HIV-positive intravenous drug abusers.

    PubMed

    von Giesen, H J; Hefter, H; Roick, H; Mauss, S; Arendt, G

    1994-12-01

    Motor tests comprising the analysis of postural tremor, most rapid voluntary alternating index finger movements (MRAM) and the rise time of most rapid index finger extensions (CT) allow us to quantify HIV-associated minor motor deficits electrophysiologically. The electrophysiological results in 57 HIV-positive individuals who acquired HIV infection by intravenous drug abuse (IVDA) were compared with those of 57 matched HIV-positive homosexuals and 98 HIV-negative controls to evaluate a possible additional influence of IVDA on motor performance. Motor deficits showed no differences between HIV-positive i.v. drug abusers and homosexuals, revealing a highly significant slowing of MRAM and prolongation of CT to an almost identical extent. Thus, in HIV-infected individuals minor motor deficits are characteristic early signs of subclinical central nervous system involvement regardless of the mode of HIV infection. PMID:7897448

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

    ERIC Educational Resources Information Center

    Shannon, Thomas A.

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

  3. Chiral all-organic nitroxide biradical liquid crystals showing remarkably large positive magneto-LC effects.

    PubMed

    Suzuki, Katsuaki; Takemoto, Yusa; Takaoka, Shohei; Taguchi, Koji; Uchida, Yoshiaki; Mazhukin, Dmitrii G; Grigor'ev, Igor A; Tamura, Rui

    2016-03-11

    The liquid crystalline chiral nitroxide biradical (S,S,S,S)-3 synthesized has shown much larger 'positive magneto-LC effects' in the chiral nematic (N*) phase than the monoradical (S,S)-1. PMID:26871609

  4. [The false positive reaction of the Triage panel drug-of-abuse by herbal drugs ma-huang (Ephedra sinica (Ephedraceae))].

    PubMed

    Nishiguchi, M; Kinoshita, H; Higasa, K; Taniguchi, T; Ouchi, H; Minami, T; Marukawa, S; Yoshinaga, K; Yamauchi, J; Aoki, S; Hishida, S

    2001-11-01

    We investigated false-positive reactions obtained from a drug screening test using a Triage panel. We detected 2 cases giving false-positive reaction for AMP (amphetamine, methamphetamine) during the screening of 187 normal subjects. Subsequent follow up testing by high-performance liquid chromatography (HPLC), showed both to be false-positive reactions. As both cases have a history of ingesting the herbal drug, Ma-huang (Ephedra sinica (Ephedraceae)), containing ephedrine, we examined the relationship between false-positive reactions on Triage and Ma-huang. All urine samples collected from 7 healthy volunteers following administration of Ma-huang indicated AMP positive on Triage. Also a high ratio of AMP positives was observed in the patients who were administered Ma-huang-containing drugs at the hospital. However, none of them were identified as true-positives by HPLC or gas chromatography mass spectrometry (GC/MS) analysis. The extract of Ma-huang contained in herbal drugs, which otherwise contain neither amphetamine nor its derivatives, gives (AMP) positive indications on Triage. We speculate that unidentified components of Ma-huang cause the false-positive reactions. We suggest that follow-up tests by GC/MS or HPLC are needed wherever a positive result is obtained from a screening test by Triage. Furthermore, it will be established to continue collecting information on prescribed and non-prescribed drugs. PMID:11905042

  5. The drug target genes show higher evolutionary conservation than non-target genes

    PubMed Central

    Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-01

    Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets. PMID:26716901

  6. Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

    PubMed

    Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

    2008-01-01

    Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease. PMID:18064727

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

    PubMed Central

    Stimpson, Jim P.; Pagán, José A.

    2014-01-01

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

  8. Predicting toxicities of reactive metabolite-positive drug candidates.

    PubMed

    Kalgutkar, Amit S; Dalvie, Deepak

    2015-01-01

    Because of the inability to predict and quantify the risk of idiosyncratic adverse drug reactions (IADRs) and because reactive metabolites (RMs) are thought to be responsible for the pathogenesis of some IADRs, the potential for RM formation within new chemical entities is routinely examined with the ultimate goal of eliminating or reducing the liability through iterative design. Likewise, avoidance of structural alerts is almost a standard practice in drug design. However, the perceived safety concerns associated with the use of structural alerts and/or RM screening tools as standalone predictors of toxicity risks may be overexaggerated. Numerous marketed drugs form RMs but do not cause idiosyncratic toxicity. In this review article, we present a critique of the structural alert/RM concept as applied in drug discovery and evaluate the evidence linking structural alerts and RMs to observed toxic effects. Pragmatic risk mitigation strategies to aid the advancement of drug candidates that carry a RM liability are also discussed. PMID:25292426

  9. The benefits of health information technology: a review of the recent literature shows predominantly positive results.

    PubMed

    Buntin, Melinda Beeuwkes; Burke, Matthew F; Hoaglin, Michael C; Blumenthal, David

    2011-03-01

    An unprecedented federal effort is under way to boost the adoption of electronic health records and spur innovation in health care delivery. We reviewed the recent literature on health information technology to determine its effect on outcomes, including quality, efficiency, and provider satisfaction. We found that 92 percent of the recent articles on health information technology reached conclusions that were positive overall. We also found that the benefits of the technology are beginning to emerge in smaller practices and organizations, as well as in large organizations that were early adopters. However, dissatisfaction with electronic health records among some providers remains a problem and a barrier to achieving the potential of health information technology. These realities highlight the need for studies that document the challenging aspects of implementing health information technology more specifically and how these challenges might be addressed. PMID:21383365

  10. African-American Youth in Public Housing Showing Low Alcohol and Drug Use.

    ERIC Educational Resources Information Center

    Rodney, H. Elaine; Mupier, Robert; O'Neal, Stephanie

    1997-01-01

    Explored the rate of alcohol and drug abuse among female and male adolescents (N=123) in public housing communities and examined risk factors leading to substance abuse. Results indicate no gender differences in alcohol or drug abuse. Poor academic performance was seen as a risk factor for alcohol abuse. (RJM)

  11. Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects.

    PubMed

    Cho, Suengmok; Kim, Sojin; Jin, Zhenhua; Yang, Hyejin; Han, Daeseok; Baek, Nam-In; Jo, Jinho; Cho, Chang-Won; Park, Ji-Hae; Shimizu, Makoto; Jin, Young-Ho

    2011-10-01

    Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolytic effect of ILTG has been reported; however, its action mechanism and hypnotic activity have not yet been demonstrated. Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG significantly potentiated the pentobarbital-induced sleep in mice at doses of 25 and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptor antagonist. The binding affinity of ILTG was 0.453 μM and was found to be higher than that of the reference compound, diazepam (DZP, 0.012 μM). ILTG (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD receptors than DZP, and the dissociation constant for ILTG was 4.0 × 10(-10)M. The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426. These results suggest that ILTG produces hypnotic effects by positive allosteric modulation of GABA(A)-BZD receptors. PMID:21945440

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

    PubMed Central

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

    2015-01-01

    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

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

    MedlinePlus

    ... Under-Prescribing Flu Antiviral Drugs and Possibly Overprescribing Antibiotics Language: English Español Recommend on Facebook Tweet ... medications. In contrast, clinicians may have overprescribed common antibiotics. The authors of the study concluded that more ...

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

    PubMed

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

    2015-10-01

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

  15. C-Kit non-mutated metastatic melanoma showing positive response to Nilotinib.

    PubMed

    Alkeraye, S; Dadban, A; Lok, C; Arnault, J P; Chaby, G

    2016-01-01

    Melanoma is an aggressive tumor with advanced disease characterized by widespread metastatic lesions and the tumor hastraditionally been resistant to most forms of treatment. Indeed, metastatic melanoma has a very poor prognosis with a median survival time of 8-9 months and an estimated 3-year survival rate of less than 15 % [1].Recent advances in our understanding of the genetic profile of melanoma cells and the molecular factors that drive malignant transformation have resulted in the identification of numerous new therapeutic targets.KIT is an established therapeutic target in cancers with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various small molecule inhibitors of KIT including imatinib mesylate [2].Nilotinib is an inhibitor of ligand-induced PDGFRα and PDFGRβ kinase activity and autophosphorylation of constitutively activated KIT harboring exon 13 or exon 11 mutations (IC50 values of 0.2 and 0.027 μmol/L, respectively), with efficacy comparable to that of imatinib [2].We report a case of non-kit mutated metastatic vaginal melanoma showing impressive response to nilotinib. PMID:26990482

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

    PubMed Central

    Lepesheva, Galina I.

    2013-01-01

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

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

    Cancer.gov

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

  18. Social support among HIV positive injection drug users: implications to integrated intervention for HIV positives.

    PubMed

    Knowlton, Amy; Hua, Wei; Latkin, Carl

    2004-12-01

    The study compared social support networks of HIV seropositive versus seronegative injection drug users (IDUs). Participants were 635 low income African Americans; 47% were HIV seropositive (of whom 17% had AIDS), 45% female, and 45% current drug users. A social network methodology elicited structural, functional, and relational network components. After controlling for confounders, HIV seropositive compared with HIV seronegative IDUs had larger support networks, including more females, kin and sources of instrumental assistance, and marginally more sources of emotional support, though they were less likely to have a sex partner. There was no difference between HIV status and number of active drug users in support networks. Results suggest that HIV seropositive IDUs had mobilized a range of network support but that they also relied on drug using social influences. Findings may have implications to the development of integrated HIV prevention and care intervention that builds on HIV seropositives' natural support structures. PMID:15690109

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

    PubMed Central

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

    1995-01-01

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

  20. Neuropsychological functioning in HIV-positive African-American women with a history of drug use.

    PubMed Central

    Mason, K. I.; Campbell, A.; Hawkins, P.; Madhere, S.; Johnson, K.; Takushi-Chinen, R.

    1998-01-01

    This preliminary investigation examined neuropsychological performance in a sample of human immunodeficiency virus (HIV)-positive and HIV-negative African-American women with a history of drug use. The study population was comprised of 10 HIV-negative, 9 asymptomatic HIV-positive, 13 symptomatic HIV-positive, and 10 acquired immunodeficiency virus (AIDS) patients. A neuropsychological battery designed to assess attention, psychomotor processing, verbal memory, and visual memory was administered to participants. No evidence of HIV-related cognitive impairment was found in patients in the early stages of HIV infection. Multivariate analyses of variance revealed significant deficits in psychomotor processing and verbal recall in persons with AIDS. These individuals showed greater difficulty in tasks requiring maintained attention and performed poorly on measures of immediate and delayed verbal recall. In contrast, HIV status was not related to visual memory, verbal recognition, or the number of errors made during a verbal recall task. The pattern of cognitive deficits observed in persons with AIDS resembles that commonly associated with subcortical pathology. The cognitive deficits observed were not related to depression or recentness of drug use. PMID:9828581

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

    PubMed

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

    2013-01-01

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

  2. Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results.

    PubMed

    Cody, John T

    2002-05-01

    Medical Review Officer interpretation of laboratory results is an important component of drug testing programs. The clinical evaluation of laboratory results to assess the possibility of appropriate medical use of a drug is a task with many different facets, depending on the drug class considered. This intercession prevents the reporting of positive results unless it is apparent that drugs were used illicitly. In addition to the commonly encountered prescribed drugs that yield positive drug testing results, other sources of positive results must be considered. This review describes a series of compounds referred to as "precursor" drugs that are metabolized by the body to amphetamine and/or methamphetamine. These compounds lead to positive results for amphetamines even though neither amphetamine nor methamphetamine were used, a possibility that must be considered in the review of laboratory results. Description of the drugs, their clinical indications, and results seen following administration are provided. This information allows for the informed evaluation of results with regard to the potential involvement of these drugs. PMID:12024689

  3. Contamination of dietary supplements and positive drug tests in sport.

    PubMed

    Maughan, R J

    2005-09-01

    The use of dietary supplements is widespread in sport and most athletes competing at the highest level of competition use some form of dietary supplementation. Many of these supplements confer no performance or health benefit, and some may actually be detrimental to both performance and health when taken in high doses for prolonged periods. Some supplements contain excessive doses of potentially toxic ingredients, while others do not contain significant amounts of the ingredients listed on the label. There is also now evidence that some of the apparently legitimate dietary supplements on sale contain ingredients that are not declared on the label but that are prohibited by the doping regulations of the International Olympic Committee and of the World Anti-Doping Agency. Contaminants that have been identified include a variety of anabolic androgenic steroids (including testosterone and nandrolone as well as the pro-hormones of these compounds), ephedrine and caffeine. This contamination may in most cases be the result of poor manufacturing practice, but there is some evidence of deliberate adulteration of products. The principle of strict liability that applies in sport means that innocent ingestion of prohibited substances is not an acceptable excuse, and athletes testing positive are liable to penalties. Although it is undoubtedly the case that some athletes are guilty of deliberate cheating, some positive tests are likely to be the result of inadvertent ingestion of prohibited substances present in otherwise innocuous dietary supplements. PMID:16195040

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2011-03-20

    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

  6. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs.

    PubMed

    Ulrichts, Hans; Silence, Karen; Schoolmeester, Anne; de Jaegere, Peter; Rossenu, Stefaan; Roodt, Jan; Priem, Sofie; Lauwereys, Marc; Casteels, Peter; Van Bockstaele, Femke; Verschueren, Katrien; Stanssens, Patrick; Baumeister, Judith; Holz, Josefin-Beate

    2011-07-21

    Neutralizing the interaction of the platelet receptor gpIb with VWF is an attractive strategy to treat and prevent thrombotic complications. ALX-0081 is a bivalent Nanobody which specifically targets the gpIb-binding site of VWF and interacts avidly with VWF. Nanobodies are therapeutic proteins derived from naturally occurring heavy-chain-only Abs and combine a small molecular size with a high inherent stability. ALX-0081 exerts potent activity in vitro and in vivo. Perfusion experiments with blood from patients with acute coronary syndrome on standard antithrombotics demonstrated complete inhibition of platelet adhesion after addition of ALX-0081, while in the absence of ALX-0081 residual adhesion was observed. In a baboon efficacy and safety model measuring acute thrombosis and surgical bleeding, ALX-0081 showed a superior therapeutic window compared with marketed antithrombotics. Pharmacokinetic and biodistribution experiments demonstrated target-mediated clearance of ALX-0081, which leads to a self-regulating disposition behavior. In conclusion, these preclinical data demonstrate that ALX-0081 combines a high efficacy with an improved safety profile compared with currently marketed antithrombotics. ALX-0081 has entered clinical development. PMID:21576702

  7. Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells

    NASA Astrophysics Data System (ADS)

    Aires, Antonio; Ocampo, Sandra M.; Simões, Bruno M.; Josefa Rodríguez, María; Cadenas, Jael F.; Couleaud, Pierre; Spence, Katherine; Latorre, Alfonso; Miranda, Rodolfo; Somoza, Álvaro; Clarke, Robert B.; Carrascosa, José L.; Cortajarena, Aitziber L.

    2016-02-01

    Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.

  8. Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells.

    PubMed

    Aires, Antonio; Ocampo, Sandra M; Simões, Bruno M; Josefa Rodríguez, María; Cadenas, Jael F; Couleaud, Pierre; Spence, Katherine; Latorre, Alfonso; Miranda, Rodolfo; Somoza, Álvaro; Clarke, Robert B; Carrascosa, José L; Cortajarena, Aitziber L

    2016-02-12

    Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully  apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro. PMID:26754042

  9. Some problems with the anti-prohibitionist position on legalization of drugs.

    PubMed

    De Leon, G

    1994-01-01

    The pro-legal position has mounted cogent arguments to support conclusions that the existing prohibition policy has failed and that legalization, while not a solution to the drug use problem, will effectively eliminate drug related crime. The premise of this article is that a legalization policy is wrong in that the basic assumptions underlying the anti-prohibitionist position are flawed. Prohibition has operated in a social vacuum. It has been an isolated effort substituting for an integrated and well coordinated approach which includes prevention, treatment as well as enforcement and supported by an educated public resolve against illicit drugs. PMID:8204674

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

    PubMed Central

    Hölscher, Christian

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users.

    PubMed

    Smith, Donald B; Simmonds, Peter; Bell, Jeanne E

    2014-02-01

    The long-term impact of chronic human immunodeficiency virus (HIV) infection on brain status in injecting drug users (IDU) treated with highly active antiretroviral therapy (HAART) is unknown. Viral persistence in the brain with ongoing neuroinflammation may predispose to Alzheimer-like neurodegeneration. In this study, we investigated the brains of ten HAART-treated individuals (six IDU and four non-DU), compared with ten HIV negative controls (six IDU and four non-DU). HIV DNA levels in brain tissue were correlated with plasma and lymphoid tissue viral loads, cognitive status, microglial activation and Tau protein and amyloid deposition. Brain HIV proviral DNA levels were low in most cases but higher in HIV encephalitis (n = 2) and correlated significantly with levels in lymphoid tissue (p = 0.0075), but not with those in plasma. HIV positive subjects expressed more Tau protein and amyloid than HIV negative controls (highest in a 58 year old), as did IDU, but brain viral loads showed no relation to Tau and amyloid. Microglial activation linked significantly to HIV positivity (p = 0.001) and opiate abuse accentuated these microglial changes (p = 0.05). This study confirms that HIV DNA persists in brains despite HAART and that opiate abuse adds to the risk of brain damage in HIV positive subjects. Novel findings in this study show that (1) plasma levels are not a good surrogate indicator of brain status, (2) viral burden in brain and lymphoid tissues is related, and (3) while Tau and amyloid deposition is increased in HIV positive IDU, this is not specifically related to increased HIV burden within the brain. PMID:24420447

  13. Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.

    PubMed

    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

    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 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. Medicare Prescription Drug Plan Enrollees Report Less Positive Experiences Than Their Medicare Advantage Counterparts.

    PubMed

    Elliott, Marc N; Landon, Bruce E; Zaslavsky, Alan M; Edwards, Carol; Orr, Nathan; Beckett, Megan K; Mallett, Joshua; Cleary, Paul D

    2016-03-01

    Since 2006, Medicare beneficiaries have been able to obtain prescription drug coverage through standalone prescription drug plans or their Medicare Advantage (MA) health plan, options exercised in 2015 by 72percent of beneficiaries. Using data from community-dwelling Medicare beneficiaries older than age sixty-four in 700 plans surveyed from 2007 to 2014, we compared beneficiaries' assessments of Medicare prescription drug coverage when provided by standalone plans or integrated into an MA plan. Beneficiaries in standalone plans consistently reported less positive experiences with prescription drug plans (ease of getting medications, getting coverage information, and getting cost information) than their MA counterparts. Because MA plans are responsible for overall health care costs, they might have more integrated systems and greater incentives than standalone prescription drug plans to provide enrollees medications and information effectively, including, since 2010, quality bonus payments to these MA plans under provisions of the Affordable Care Act. PMID:26953300

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

    PubMed

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

    2015-05-01

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

  18. Profiling antibody drug conjugate positional isomers: a system-of-equations approach.

    PubMed

    Le, Lan N; Moore, Jamie M R; Ouyang, Jun; Chen, Xiaoying; Nguyen, Mary D H; Galush, William J

    2012-09-01

    Antibody drug conjugates enable the targeted delivery of potent chemotherapeutic agents directly to cancerous cells. They are made by the chemical conjugation of cytotoxins to monoclonal antibodies, which can be achieved by first reducing interchain disulfide bonds followed by conjugation of the resulting free thiols with drugs. This process yields a controlled, but heterogeneous, population of conjugated products that contains species with various numbers of drugs linked to different former interchain disulfide cysteine residues on the antibodies. We have developed a mathematical approach using inputs from capillary electrophoresis and hydrophobic interaction chromatography to determine the positional isomer distribution within a population of antibody drug conjugates. The results are confirmed by analyzing isolated samples of specific drug-to-antibody ratio species. The procedure is amenable to rapid determination of positional isomer distributions and features low material requirements. A survey of several antibody drug conjugates based on the same IgG framework and small molecule drug combination has shown a very similar distribution of isomers among all of the molecules using this technique, suggesting a robust conjugation process. PMID:22913809

  19. Positive Youth Development: Helping Postsecondary Students Deal with Pressures To Use Alcohol and Other Drugs.

    ERIC Educational Resources Information Center

    Guthmann, Debra S.; Sandberg, Katherine A.

    Current research shows alcohol and other drugs to be a major problem on postsecondary campuses despite the fact that the purchase and use of alcohol is illegal for many college students and on most campuses. Little is known about drug and alcohol use levels among deaf students, many of whom come to college ill prepared to handle the pressures of…

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

    PubMed

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

    2009-07-01

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

  1. Novel Luminex Assay for Telomere Repeat Mass Does Not Show Well Position Effects Like qPCR

    PubMed Central

    Jasmine, Farzana; Roy, Shantanu; Ahsan, Habibul; Pierce, Brandon L.

    2016-01-01

    Telomere length is a potential biomarker of aging and risk for age-related diseases. For measurement of relative telomere repeat mass (TRM), qPCR is typically used primarily due to its low cost and low DNA input. But the position of the sample on a plate often impacts the qPCR-based TRM measurement. Recently we developed a novel, probe-based Luminex assay for TRM that requires ~50ng DNA and involves no DNA amplification. Here we report, for the first time, a comparison among TRM measurements obtained from (a) two singleplex qPCR assays (using two different primer sets), (b) a multiplex qPCR assay, and (c) our novel Luminex assay. Our comparison is focused on characterizing the effects of sample positioning on TRM measurement. For qPCR, DNA samples from two individuals (K and F) were placed in 48 wells of a 96-well plate. For each singleplex qPCR assay, we used two plates (one for Telomere and one for Reference gene). For the multiplex qPCR and the Luminex assay, the telomere and the reference genes were assayed from the same well. The coefficient of variation (CV) of the TRM for Luminex (7.2 to 8.4%) was consistently lower than singleplex qPCR (11.4 to 14.9%) and multiplex qPCR (19.7 to 24.3%). In all three qPCR assays the DNA samples in the left- and right-most columns showed significantly lower TRM than the samples towards the center, which was not the case for the Luminex assay (p = 0.83). For singleplex qPCR, 30.5% of the variation in TL was explained by column-to-column variation and 0.82 to 27.9% was explained by sample-to-sample variation. In contrast, only 5.8% of the variation in TRM for the Luminex assay was explained by column-to column variation and 50.4% was explained by sample-to-sample variation. Our novel Luminex assay for TRM had good precision and did not show the well position effects of the sample that were seen in all three of the qPCR assays that were tested. PMID:27182778

  2. Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone.

    PubMed

    Syed, Husnain; Som, Sumit; Khan, Nazia; Faltas, Wael

    2009-01-01

    The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving. PMID:21686586

  3. Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone

    PubMed Central

    Syed, Husnain; Som, Sumit; Khan, Nazia; Faltas, Wael

    2009-01-01

    The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving. PMID:21686586

  4. Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

    PubMed

    de Castro-Sobrinho, Juçara Maria; Rabelo-Santos, Silvia Helena; Fugueiredo-Alves, Rosane Ribeiro; Derchain, Sophie; Sarian, Luis Otávio Z; Pitta, Denise R; Campos, Elisabete A; Zeferino, Luiz Carlos

    2016-02-01

    Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥20% of clue cells. Present inflammatory response was defined as ≥30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia. Diagn. Cytopathol. 2016;44:80-86. © 2015 Wiley Periodicals, Inc. PMID:26644228

  5. Trastuzumab-mediated selective delivery for platinum drug to HER2-positive breast cancer cells.

    PubMed

    Huang, Rong; Sun, Yu; Gao, Qihe; Wang, Qiucui; Sun, Baiwang

    2015-10-01

    Oxaliplatin is used widely as an anticancer drug for clinical treatment. However, its applications are limited because of its poor selectivity. In this work, we described the design, synthesis, and characterization of conjugates combining trastuzumab with a platinum (IV) analog of oxaliplatin, in which the trastuzumab acted as an active targeting agent for HER2-positive cancer cells. Indirect enzyme-linked immunosorbent assay and immunofluorescence study indicated the platinum (IV)-trastuzumab conjugates retained specific binding activity to HER2 overexpressed SK-BR-3 cells. In the presence of ascorbic acid, platinum (IV)-trastuzumab conjugates were reduced to platinum (II) analogs, which could bind to and unwind PUC19 DNA in a manner similar to oxaliplatin. The cytotoxic study was tested on three breast cell lines: SK-BR-3, MCF-7, and MDA-MB-231. Platinum (IV)-trastuzumab conjugates showed promising antiproliferative activity against SK-BR-3 cells, but significantly decreased the inhibition to MDA-MB-231 and MCF-7 cells. The flow cytometric analysis showed that the conjugates arrested the cell cycle mainly at the G2/M phase and killed the cells through an apoptotic pathway. PMID:26186063

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

    PubMed Central

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

    2013-01-01

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

  7. Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.

    PubMed

    Burdon, William M; St De Lore, Jef; Prendergast, Michael L

    2011-09-01

    Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention. PMID:22185038

  8. Developing and Implementing a Positive Behavioral Reinforcement Intervention in Prison-Based Drug Treatment: Project BRITE

    PubMed Central

    Burdon, William M.; De Lore, Jef St.; Prendergast, Michael L.

    2012-01-01

    Within prison settings, the reliance on punishment for controlling inappropriate or non-compliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention. PMID:22185038

  9. Cluster of oral atypical Candida albicans isolates in a group of human immunodeficiency virus-positive drug users.

    PubMed Central

    Boerlin, P; Boerlin-Petzold, F; Durussel, C; Addo, M; Pagani, J L; Chave, J P; Bille, J

    1995-01-01

    Twenty-one chlamydospore-forming and germ tube-positive Candida albicans clinical isolates from 15 human immunodeficiency virus (HIV)-positive and 3 HIV-negative patients were examined by two different genetic methods. Multilocus enzyme electrophoresis and hybridization with the C. albicans-specific Ca3 probe showed that such isolates can be split into two genetically distinct groups that can be clearly distinguished. One group mainly contained strains with atypical sugar assimilation patterns and could be distinguished from the other group by the absence of intracellular beta-glucosidase activity. All 13 strains belonging to this group were isolated from the oral cavities of asymptomatic HIV-positive drug users and may be less pathogenic than the eight strains from the other group isolated either from HIV-positive patients with oropharyngeal candidiasis or from HIV-negative patients with invasive candidiasis. PMID:7615716

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

    PubMed

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

    2015-12-01

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

  11. Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam.

    PubMed

    Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Do, Nhan Thi; Nguyen, Long Thanh; Mills, Steve; Houston, Stan; Jacobs, Philip

    2012-01-01

    Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six and nine months. Costs of MMT services were analyzed and converted to the year 2009. Quality-adjusted life years (QALYs) were modeled from changes in health-related quality of life of patients using the modified World Health Organization Quality of Life - Brief Version (WHOQOL-BREF). Inverse probability-of-treatment weights, constructed using propensity score of non-responses, were applied to adjust for potential confounding. Over nine months, MMT substantially improved QALYs of HIV/AIDS patients (0.076 QALY [0.066-0.084]). The increments in QALY were large and stabilized in those patients taking antiretroviral treatment and abstinent to drug use. For one QALY gained, the MMT program would cost US$3745.3, approximately 3.2 times Vietnam GDP per capita in 2009. The cost-effectiveness of MMT intervention was robust against HIV advanced status or co-morbidity, e.g., TB treatment, but it might not be cost-effective for those patients who continued to use drug. Findings of this study indicate that providing MMT for HIV-positive drug users is a cost-effective intervention in Vietnam. Integrating MMT to HIV/AIDS care and treatment services would be beneficial in injection-driven HIV epidemics. PMID:21936718

  12. [Positive side-effects of antibiotic and antimicrobial drugs in therapy (author's transl)].

    PubMed

    Illig, L

    1979-01-01

    Since about 1950 especially, dermatologists world-wide have been utilizing the positive side-effects, discovered by chance, of all groups of antibiotic and antimicrobial drugs. These drugs are used to treat certain non-microbially induced dermatoses, without any knowledge of the mechanisms involved. A short history is given and the most important drugs and the indications for their use are described. The following drugs are undoubtedly effective and sometimes even the therapy of choice: tetracyclines in acne vulgaris and rosacea (including rosacea keratitis); penicillin G in acrodermatitis atrophicans and cold urticaria; dapsone in dermatitis herpetiformis and - as a powerful adjuvant - in acne vulgaris and rosacea. Before the discovery of the socalled immunodepressive drugs, tetracycline was the only alternative to - or at least a highly effective adjuvant of - cortisone in dermatomyositis and chloroquine in localised and systemic lupus erythematosus. Finally, clioquinole was life-saving in acrodermatitis continua in children until this condition was recently identified as a zinc-deficiency syndrome. Therapeutical mechanisms have been found only in the case of acne, rosacea and dermatitis herpetiformis. In most other diseases the nature of the therapeutical effectiveness of antibiotic and antimicrobial drugs still remains a mystery. PMID:162143

  13. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies.

    PubMed

    Patsalos, Philip N; Berry, David J; Bourgeois, Blaise F D; Cloyd, James C; Glauser, Tracy A; Johannessen, Svein I; Leppik, Ilo E; Tomson, Torbjörn; Perucca, Emilio

    2008-07-01

    Although no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin. PMID:18397299

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Anderson, Jeffrey M

    2011-07-01

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

  16. Position paper from the Spanish Society of Rheumatology on biosimilar drugs.

    PubMed

    Abad Hernández, Miguel Ángel; Andreu, José Luis; Caracuel Ruiz, Miguel Ángel; Belmonte Serrano, Miguel Ángel; Díaz-González, Federico; Moreno Muelas, José Vicente

    2015-01-01

    A biosimilar (BS) is a biological drug that contains a version of the active substance of an already authorized original biological product. The BSs are marketed after patent period of the original drug has ended and once it has been demonstrated that the differences regarding the innovative medicine have no relevant effect on its safety or clinical efficacy. The Spanish Society of Rheumatology, in line with the European Medicines Agency, considers that because of its nature and complexity of production, a BS cannot be considered to be the same as a generic drug. The Spanish Society of Rheumatology expresses an unequivocal commitment to the sustainability of the health system in our country and our steadfast alignment with all measures designed to ensure continuity, without reducing the quality of care. Therefore, we believe that the advent of BSs will likely facilitate access of patients with rheumatic diseases to the biological drugs. This article reviews the European Medicines Agency requirements for authorization, the Spanish legal framework and controversies on BS and presents the position paper of the Spanish Society of Rheumatology on these drugs. PMID:25982595

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

    PubMed

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

    2015-07-01

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

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

    ERIC Educational Resources Information Center

    DiGiulio, Robert

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

  19. An Allosteric Modulator of HIV-1 Protease Shows Equipotent Inhibition of Wild-Type and Drug-Resistant Proteases

    PubMed Central

    2015-01-01

    NMR and MD simulations have demonstrated that the flaps of HIV-1 protease (HIV-1p) adopt a range of conformations that are coupled with its enzymatic activity. Previously, a model was created for an allosteric site located between the flap and the core of HIV-1p, called the Eye site (Biopolymers2008, 89, 643−65218381626). Here, results from our first study were combined with a ligand-based, lead-hopping method to identify a novel compound (NIT). NIT inhibits HIV-1p, independent of the presence of an active-site inhibitor such as pepstatin A. Assays showed that NIT acts on an allosteric site other than the dimerization interface. MD simulations of the ligand–protein complex show that NIT stably binds in the Eye site and restricts the flaps. That bound state of NIT is consistent with a crystal structure of similar fragments bound in the Eye site (Chem. Biol. Drug Des.2010, 75, 257−26820659109). Most importantly, NIT is equally potent against wild-type and a multidrug-resistant mutant of HIV-1p, which highlights the promise of allosteric inhibitors circumventing existing clinical resistance. PMID:25062388

  20. DJ Pairing during VDJ Recombination Shows Positional Biases That Vary among Individuals with Differing IGHD Locus Immunogenotypes.

    PubMed

    Kidd, Marie J; Jackson, Katherine J L; Boyd, Scott D; Collins, Andrew M

    2016-02-01

    Human IgH diversity is influenced by biases in the pairing of IGHD and IGHJ genes, but these biases have not been described in detail. We used high-throughput sequencing of VDJ rearrangements to explore DJ pairing biases in 29 individuals. It was possible to infer three contrasting IGHD-IGHJ haplotypes in nine of these individuals, and two of these haplotypes include deletion polymorphisms involving multiple contiguous IGHD genes. Therefore, we were able to explore how the underlying genetic makeup of the H chain locus influences the formation of particular DJ pairs. Analysis of nonproductive rearrangements demonstrates that 3' IGHD genes tend to pair preferentially with 5' IGHJ genes, whereas 5' IGHD genes pair preferentially with 3' IGHJ genes; the relationship between IGHD gene pairing frequencies and IGHD gene position is a near linear one for each IGHJ gene. However, striking differences are seen in individuals who carry deletion polymorphisms in the D locus. The absence of different blocks of IGHD genes leads to increases in the utilization frequencies of just a handful of genes, and these genes have no clear positional relationships to the deleted genes. This suggests that pairing frequencies may be influenced by additional complex positional relationships that perhaps arise from chromatin structure. In contrast to IGHD gene usage, IGHJ gene usage is unaffected by the IGHD gene-deletion polymorphisms. Such an outcome would be expected if the recombinase complex associates with an IGHJ gene before associating with an IGHD gene partner. PMID:26700767

  1. Predictors of hospitalization for HIV-positive women and men drug users, 1996-2000.

    PubMed Central

    Schoenbaum, Ellie E.; Lo, Yungtai; Floris-Moore, Michelle

    2002-01-01

    OBJECTIVE: This study sought to determine whether health outcomes differed by gender in a cohort of African American, Hispanic American, and white drug users. METHODS: The authors studied hospitalization rates and discharge diagnoses in the HERO Study, an ongoing prospective study of drug users that included HIV-positive and HIV-negative opiate users. The data are from 1996-2000, when highly active antiretroviral therapy (HAART) was available. RESULTS: Women had higher rates of hospitalization than men independent of HIV status, and there was no association between ethnicity and hospitalization. Being a woman was an independent risk factor for HIV and non-HIV-related hospitalization. CONCLUSION: Health disparities between men and women extend to HIV. PMID:12435828

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

    PubMed

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

    2015-02-18

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

  3. CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies.

    PubMed

    Han, Tae H; Gopal, Ajay K; Ramchandren, Radhakrishnan; Goy, Andre; Chen, Robert; Matous, Jeffrey V; Cooper, Maureen; Grove, Laurie E; Alley, Stephen C; Lynch, Carmel M; O'Connor, Owen A

    2013-08-01

    Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells. This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE. Two 21-day cycles of brentuximab vedotin (1.2 or 1.8 mg/kg intravenously) were administered to 56 patients with CD30-positive hematologic malignancies. Each patient also received either a sensitive CYP3A substrate (midazolam), an effective inducer (rifampin), or a strong inhibitor (ketoconazole). Brentuximab vedotin did not affect midazolam exposures. ADC exposures were unaffected by concomitant rifampin or ketoconazole; however, MMAE exposures were lower with rifampin and higher with ketoconazole. The short-term safety profile of brentuximab vedotin in this study was generally consistent with historic clinical observations. The most common adverse events were nausea, fatigue, diarrhea, headache, pyrexia, and neutropenia. Over a 1-week period, ∼23.5% of intact MMAE was recovered after administration of brentuximab vedotin; all other species were below the limit of quantitation. The primary excretion route is via feces (median 72% of the recovered MMAE). These results suggest that brentuximab vedotin (1.8 mg/kg) and MMAE are neither inhibitors nor inducers of CYP3A; however, MMAE is a substrate of CYP3A. PMID:23754575

  4. Genomic Analysis Identifies Targets of Convergent Positive Selection in Drug Resistant Mycobacterium tuberculosis

    PubMed Central

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

    2013-01-01

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

  5. Novel antimicrobial agents against multi-drug-resistant gram-positive bacteria: an overview.

    PubMed

    Giannakaki, Venetia; Miyakis, Spiros

    2012-12-01

    Antimicrobial resistance threatens to compromise the treatment of bacterial infectious diseases. Strains resistant to most (if not all) antibiotics available have emerged. Gram-positive such representatives include strains of Methicillinresistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE) and highly-resistant to penicillin Streptococcus pneumoniae. Although the phenomenon of antimicrobial drug resistance is expanding, limited number of new antibiotics has been successfully developed in the last few decades. Several novel antimicrobial agents, however, are currently in diverse phases of development and undergoing clinical trials. This review will summarize the main candidates for novel antibacterial agents active against Gram-positive multi-resistant pathogens along with the discussion of some patents relevant to the topic. PMID:23016758

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

    PubMed Central

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

    2009-01-01

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

  7. Pulmonary arterial hypertension in adults: novel drugs and catheter ablation techniques show promise? Systematic review on pharmacotherapy and interventional strategies.

    PubMed

    Rosanio, Salvatore; Pelliccia, Francesco; Gaudio, Carlo; Greco, Cesare; Keylani, Abdul M; D'Agostino, Darrin C

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-02-01

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

  10. Intimate partner violence perpetration against main female partners among HIV-positive male injection drug users.

    PubMed

    Frye, Victoria; Latka, Mary H; Wu, YingFeng; Valverde, Eduardo E; Knowlton, Amy R; Knight, Kelly R; Arnsten, Julia H; O'Leary, Ann

    2007-11-01

    Intimate partner violence (IPV) against women is a serious public health and social problem and is associated with a host of adverse health outcomes and behaviors, HIV risk behaviors included, among women who are victimized. Historically, research has focused on correlates of IPV victimization among women; thus, there is less information on the role of men in perpetrating IPV, particularly among men at risk for transmitting HIV to their female partners. We assessed the self-reported prevalence and correlates of perpetration and threat of perpetration of physical and/or sexual IPV against a main female partner among 317 HIV-positive men who were current injection drug users (IDUs). More than 40% of men reported perpetrating physical (39%) and/or sexual (4%) violence against their main female partners in the past year. Multivariate analyses revealed that low education, homelessness, psychologic distress, and unprotected sex with main and nonmain HIV-negative female partners were positively associated with IPV perpetration against main female partners. These findings reveal that IPV perpetration is prevalent among HIV-positive male IDUs and associated with sexual HIV transmission risk behaviors. IPV assessment and treatment among HIV-positive men in HIV care is recommended as a way to prevent IPV perpetration and victimization and to reduce potential HIV transmission. PMID:18089979

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Copeland, Lorraine

    2004-01-01

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

  13. A Retrospective Analysis of Urine Drugs of Abuse Immunoassay True Positive Rates at a National Reference Laboratory.

    PubMed

    Johnson-Davis, Kamisha L; Sadler, Aaron J; Genzen, Jonathan R

    2016-03-01

    Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ∼14%, ∼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey. PMID:26668238

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

    PubMed

    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

    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

  15. Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

    PubMed Central

    Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

    2012-01-01

    In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ?10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM. PMID:22829966

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    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

  19. Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi.

    PubMed

    van Oosterhout, J J; Dzinjalamala, F K; Dimba, A; Waterhouse, D; Davies, G; Zijlstra, E E; Molyneux, M E; Molyneux, E M; Ward, S

    2015-10-01

    Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/μl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 μg/ml (2.474 to 5.596 μg/ml), area under the curve from 0 to 24 h (AUC0-∞) of 21.32 μg/ml · h (13.57 to 28.60 μg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 μg/ml (2.979 to 4.544 μg/ml), AUC0-24 of 22.5 (14.75 to 34.59 μg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 μg/ml (30.00 to 41.60 μg/ml), AUC0-24 of 386.6 μg/ml · h (320.0 to 463.7 μg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 μg/ml (1.694 to 3.098 μg/ml), AUC0-24 of 20.41 μg/ml · h (16.18 to 26.27 μg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which the Cmax and AUC0-24 values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P = 0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further. PMID:26248378

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

    ERIC Educational Resources Information Center

    Valle, Maribel; Levy, Judith

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Porous polyurea network showing aggregation induced white light emission, applications as biosensor and scaffold for drug delivery.

    PubMed

    Bhunia, Subhajit; Chatterjee, Nabanita; Das, Subhadip; Das Saha, Krishna; Bhaumik, Asim

    2014-12-24

    We have designed a urea functionalized novel nanoporous material, POP-PU, which showsaggregation induced white light emission in the presence of suitable polar solvents. This nanomaterial has been explored as a pseudowhite light emitter where the polymeric luminogen moiety can interact with the suitable polar solvent, leading to charge transfer. Thus, solvent assisted rotational freezing of nonrigid polymeric nanoparticles gives radiative emission and the whole solution emits white light with color temperature of 8533 K. This nanoporous material also holds the pockets (donor-donor-acceptor array) for specific biomolecular interaction. Among three pyrimidine based nucleotide bases, only cytosine can amplify the PL emission intensity of POP-PU and the other two bases cannot, suggesting its future potential as a biosensor. Further, this urea functionalized porous organic nanomaterial can be utilized as an efficient drug-delivery vehicle for liver cancer diagnostics and therapy based on the specific biomolecular interaction at its surface. PMID:25459383

  3. Cancer Drugs Provide Positive Value In Nine Countries, But The United States Lags In Health Gains Per Dollar Spent.

    PubMed

    Salas-Vega, Sebastian; Mossialos, Elias

    2016-05-01

    Cancer drugs account for a growing share of health care expenditure, raising questions about how much value is gained from their use. We used a proprietary international data set to examine real-world cancer drug consumption and expenditure in the period 2004-14 in Australia, Canada, France, Germany, Italy, Japan, Sweden, the United Kingdom, and the United States and to explore the value obtained. Even after adjusting for population and epidemiological factors, we found that the United States spent more than the other countries on cancer drugs, yet it often had lower utilization. All nine countries-most notably France and Japan-witnessed an improvement in neoplasm-related years of potential life lost, which suggests that although the costs of drugs have risen, their therapeutic benefits have increased as well. Net economic value derived from cancer drug expenditures appears to have remained positive, with base-case analyses indicating that the United States obtained an estimated $32.6 billion in net positive return from cancer drug care in 2014. However, the United States lags behind other countries in health gains obtained per dollar spent on cancer drugs, which suggests an opportunity to improve value in the oncology drug market. PMID:27140987

  4. [HIV prevention in HIV-positive drug addicts. A methadone-supported model].

    PubMed

    Oertle, D; Edelmann, R; Ostewalder, J; Vernazza, P L; Galeazzi, R L

    1993-12-01

    In Switzerland, an estimated 15-25% of intravenous drug users (IVDUs) are infected with human immunodeficiency virus (HIV). It has been suggested that reduction of HIV-transmission-prone behavior could be achieved in so-called "early intervention programs". Few public prevention programs have so far been targeted to HIV-infected IVDUs. Socially marginalized, jobless, street-based, HIV-infected IVDUs are those hardest to reach for education programs: it was the hypothesis that they can be motivated for HIV-prevention efforts by methadone-based comprehensive social and medical care. The program was established by integrating one additional social worker in an outpatient clinic for infectious diseases in St. Gallen, a city with a population of 70,000 inhabitants in eastern Switzerland. Access to the 29 clients of this study (10 women, 19 men) was facilitated by offering methadone treatment (follow-up 5 to 29 months). Abstinence from additional illegal drugs was not required. Methadone, plus social care and medical treatment was provided by a small team consisting of a social worker, a physician and a nurse. A gradual approach was chosen to establish a working relationship with clients. The first attempt was to satisfy basic medical needs, housing, and financial support as well as to strengthen relevant personal relationships. Once trusting cooperation was established, reduction of transmission-prone behavior was targeted. The results show that social performance can be greatly improved by integrated social, psychological and medical assistance: for the 16 initially homeless housing was found, 14 found a job and for all but 2 basic financial support was eventually guaranteed. Self-reported drug abuse was markedly reduced, as was transmission-prone behavior by prostitution, unsafe sex practices, needle sharing and improper disposal of used syringes. Breaking the isolation of socially marginalized IVDUs seems to be the important move to enhance their social responsibility as carriers of HIV. PMID:8272803

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this... 10 Energy 4 2010-01-01 2010-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of...

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

    PubMed Central

    Lee, Tak Yan

    2011-01-01

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

  7. Construction of an integrated positive youth development conceptual framework for the prevention of the use of psychotropic drugs among adolescents.

    PubMed

    Lee, Tak Yan

    2011-01-01

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

  8. Multicentric Castleman's Disease in a Hepatitis C-Positive Intravenous Drug User: A Case Report.

    PubMed

    Talukder, D Y; Delpachitra, S N

    2011-01-01

    Introduction. We report a rare presentation of Castleman's disease in a hepatitis C-positive patient and present a short review of treatments described in other similar case reports and studies. Case Presentation. A 46-year-old male with untreated hepatitis C and a 16-year history of intravenous drug use presented with pleuritic chest pain and bony pain in the knee, hip, and lower back, on a background of unexplained weight loss of 40 kilograms, fevers, night sweats, and repeated infections over the last two years. Examination discovered tender hepatomegaly, a warm right knee effusion, and painless lymphadenopathy. The patient was reactive to Epstein Barr virus and cytomegalovirus; however, HIV and HHV-8 viral testing was negative. Osteomyelitis of vertebrae T8-T11 and septic arthritis of the knee were found on investigation. A lymph node biopsy revealed histology suggestive of plasmacytic Castleman's disease. The patient is to commence rituximab treatment. Conclusion. Castleman's disease continues to present in novel ways, which may lead to difficulties in clinicopathologic diagnosis. A growing body of evidence suggests larger studies are required to determine the best treatment for multicentric Castleman's disease, particularly in patients with a concomitant disease, including hepatitis C. PMID:21577263

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Trouet, V.; Babst, F.

    2014-12-01

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

  11. Interaction of (+)-amphetamine with cerebral dopaminergic neurones in two strains of mice, that show different temperature responses to this drug

    PubMed Central

    Caccia, S.; Cecchetti, G.; Garattini, S.; Jori, A.

    1973-01-01

    1. (+)-Amphetamine sulphate elicits a dose-dependent hyperthermia in NMRI mice but it does not significantly increase the body temperature of C3H mice. 2. When low doses of (+)-amphetamine are given, the body temperature of C3H mice decreases. 3. (+)-Amphetamine decreases the noradrenaline concentration in the brain-stem and increases the homovanillic acid concentration (HVA) in the striatum of NMRI mice, but only slightly reduces the noradrenaline concentration and does not change the HVA concentration in the brains of C3H mice. 4. The two strains appear to show a difference in the metabolism of dopamine in the striatum. The rates at which dopamine disappears from the tissue after blocking catecholamine synthesis with α-methyltyrosine and the rates at which HVA accumulates after blocking the active transport of this metabolite out of the brain with probenecid suggest that the turnover of dopamine is lower in C3H mice than in NMRI mice. PMID:4777703

  12. A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment

    PubMed Central

    Gaburro, Stefano; Stiedl, Oliver; Giusti, Pietro; Sartori, Simone B.; Landgraf, Rainer; Singewald, Nicolas

    2011-01-01

    Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments. PMID:21320392

  13. Thermodynamic origin of the solubility profile of drugs showing one or two maxima against the polarity of aqueous and nonaqueous mixtures: niflumic acid and caffeine.

    PubMed

    Bustamante, Pilar; Navarro, J; Romero, S; Escalera, B

    2002-03-01

    The purpose of this work was to investigate the origin of the different solubility profiles of drugs against the polarity of solvent mixtures with a common cosolvent. Niflumic acid and caffeine where chosen as model drugs. The solubilities were measured at five or six temperatures in aqueous (ethanol-water) and nonaqueous (ethyl acetate-ethanol) mixtures. The enthalpies of solution were obtained at the harmonic mean of the experimental temperature. Solid phase changes were analyzed using differential scanning calorimetry and thermomicroscopy. A single solubility maximum was obtained for niflumic acid against the solubility parameter of both mixtures that is not related to solid phase changes. In contrast, caffeine displays two maxima and anhydrous-hydrate transition occurs at the solubility peak in the amphiprotic mixture. The apparent enthalpies of solution of both drugs show endothermic maxima against solvent composition that are related to hydrophobic hydration. A general explanation for the cosolvent action in aqueous mixtures is proposed. The dominant mechanism shifts from entropy to enthalpy at a certain cosolvent ratio dependent on the hydrophobicity and the solubility parameter of the drug. Niflumic acid and caffeine show enthalpy-entropy compensation in ethanol-water, and this relationship is demonstrated for the first time in nonaqueous mixtures. The results support that enthalpy-entropy compensation is a general effect for the solubility of drugs in solvent mixtures. The shape of the solubility curves is correlated with the compensation plots. The solubility peaks separate different enthalpy-entropy relationships that also differentiate the solubility behavior of the hydrate and the anhydrous forms of caffeine. PMID:11920772

  14. Aggressive CD5-positive diffuse large B cell lymphoma showing c-myc rearrangements developed in a patient with autoimmune hemolytic anemia.

    PubMed

    Sonoki, T; Matsuzaki, H; Asou, N; Hata, H; Matsuno, F; Yoshida, M; Nagasaki, A; Kuribayashi, N; Kudo, H; Takatsuki, K

    1996-01-01

    A case of CD5-positive diffuse large cell lymphoma in a patient with autoimmune hemolytic anemia (AIHA) is reported. The patient was diagnosed with AIHA in December 1988. Three and a half years later, the patient complained of fever and left sided flank pain. Abnormal lymphocytes appeared in the peripheral blood and were positive for HLA-DR, CD5, CD19, CD20, and surface immunoglobulin (mu, lambda). The pathological diagnosis of the cervical lymphnode was non-Hodgkin lymphoma; diffuse large cell type with a starry sky-like appearance. Although the 8q24 translocation was not detected by karyotypic analysis of the peripheral blood mononuclear cells (PBMNC), Southern blot analysis revealed that the c-myc rearrangements had occurred. This case showed two rearranged bands with Eco RI, Bam HI, or Bgl II digestion, and a germline band with Hin dIII digestion using a second exon fragment of the c-myc gene as a probe. Despite intensive chemotherapy, this patient died 6 months after being diagnosed with malignant lymphoma. We discuss the c-myc rearrangements in this aggressive CD5-positive diffuse large B cell lymphoma. PMID:8713579

  15. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (HRP), codified at 10 CFR part 712. HRP employees will be subject to the drug testing standards of this...) Firefighters; (iii) Protective force personnel, exclusive of those covered in paragraphs (b)(1) or (b)(2)...

  16. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  19. Biosimilar drugs in Mexico: position of the Mexican College of Rheumatology, 2012.

    PubMed

    Espinosa Morales, Rolando; Díaz Borjón, Alejandro; Barile Fabris, Leonor Adriana; Esquivel Valerio, Jorge Antonio; Medrano Ramírez, Gabriel; Arce Salinas, César Alejandro; Barreira Mercado, Eduardo Rubén; Cardiel Ríos, Mario Humberto; Díaz Jouanen, Efraín; Flores Murrieta, Francisco Javier; Fraga Mouret, Antonio; Garza Elizondo, Mario Alberto; Luján Estrada, Miguel; Muñoz Barradas, Francisco José; Talavera Piña, Juan Osvaldo; Vera Lastra, Olga Lidia

    2013-01-01

    Biotechnological drugs (BTDs) are complex molecules whose manufacturing process precludes the ability to identically reproduce the structure of the original product, and therefore there cannot be an absolute equivalence between the original (innovative) medication and its biosimilar counterpart. BTDs have been proven useful in the treatment of several rheumatic diseases, however their high cost has prevented their use in many patients. Several BTD patents have expired or are close to expire, triggering the development of structurally similar drugs with efficacy and safety profiles comparable to the innovative compound; however, these must be evaluated through evidence based medicine. The Mexican General Health Law contemplates the registry of these biosimilar drugs for their use in our country. This document is a forethought from members of the Mexican College of Rheumatology, pharmacologists, and epidemiologists, in accordance with Mexican health authorities regarding the necessary scientific evidence required to evaluate the efficacy and safety of biosimilar drugs before and after their arrival to the Mexican market. PMID:23395225

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

    PubMed

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

    2015-02-15

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

  1. Risk Factors for Distress in the Adolescent Children of HIV-positive and HIV-negative Drug-Abusing Fathers

    PubMed Central

    Brook, David W.; Brook, Judith S.; Rubenstone, Elizabeth; Zhang, Chenshu; Castro, Felipe G.; Tiburcio, Nelson

    2013-01-01

    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 modeling tested an hypothesized model linking paternal latent variables, ecological factors, and adolescent substance use to adolescent distress. Results demonstrated a direct pathway between paternal and adolescent distress, as well as an indirect pathway; namely, paternal distress was linked with 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 for 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 programs for the children of drug-abusing fathers. PMID:18278619

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

    PubMed

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

    2008-01-01

    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

  3. A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma.

    PubMed

    Kurisaki-Arakawa, Aiko; Saito, Tsuyoshi; Takahashi, Michiko; Mitani, Keiko; Fukumura, Yuki; Nagashima, Yoji; Argani, Pedrum; Yao, Takashi

    2013-01-01

    Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT-PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced with the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results. PMID:24228124

  4. Coronary Heart Disease (CHD) Risk Factors and Metabolic Syndrome in HIV-Positive Drug Users in Miami

    PubMed Central

    Baum, Marianna K; Rafie, Carlin; Lai, Shenghan; Xue, Lihua; Sales, Sabrina; Page, J. Bryan; Berkman, Ronald; Karas, Linden; Campa, Adriana

    2008-01-01

    The frequency of coronary heart disease (CHD) is increasing among HIV seropositive persons. This phenomenon may be related to HIV disease itself, the use of antiretroviral medications and increased length of survival, or the synergism of these factors. In this study we have calculated the 10-year CHD risk estimate and the prevalence of metabolic syndrome in a cohort of 118 HIV seropositive chronic drug users, including those who are on HAART with or without protease inhibitors (PI). The results showed that the 10-year coronary heart disease risk among the HIV seropositive drug users was 4.8 ± 5.7, which is within the range of results published for other HIV infected cohorts. The 10-year CHD risk was significantly higher in men (5.9±6.1, p<0.001) than in women (1.7±2.4), due to their gender and the pre-menopausal mean age of the women (39.4±7.3 years of age), despite a significantly higher rate of abdominal obesity (54.8% in women vs. 8.1% in men, p<0.001) and lower HDL (61.3% in women vs. 40% in men, p=0.042). The rate of metabolic syndrome among our female HIV seropositive drug users was significantly higher (29% vs 10.3%, p=0.013) compared to men (10.3%). Participants with metabolic syndrome had a significantly higher 10-year CHD risk (27.8% vs. 10.2%, p=0.041) and higher mean BMI (28.6 ± 4.1 vs. 24.2±4, p<0.001) than those without the syndrome. The predominant proportion of the cohort had a high viral load, suggesting that their use of illicit drugs has an influence on either adherence or effectiveness of antiretroviral medication. Increased viral load was significantly associated with metabolic syndrome (OR=2.23, 95% CI:1.12, 4.47; p=0.023), high fasting glucose (OR=1.61, 95% CI: 1.02, 2.55; p=0.042) and low HDL levels (OR=1.41, 95% CI: 1.01, 1.98; p=0.046), after controlling for age gender, smoking, PI exposure, BMI and CD4. HAART with or without PI did not significantly impact the 10-year CHD risk estimate or metabolic syndrome in this cohort. The estimated effect of PI, however, was positively and significantly related to triglyceride levels (effect estimate=95.81; 95% CI:39.40, 152.21; p<0.01) after controlling for age, gender, smoking, viral load, CD4 cell count and BMI. Heavy use of cigarettes and crack/cocaine was inversely associated with obesity (OR=0.84, 95% CI:0.67, 0.99; p=0.049; OR=0.43, 95% CI:0.19, 0.98; p=0.044, respectively), while use of marijuana tended to be associated with increased central obesity (p=0.08). Heavy cigarette smoking was significantly associated with low HDL (OR=3.06, 95% CI:1.18; 7.95, p=0.02). The significant association of higher viral load with CHD risk indicates that controlling viral load may be important in reducing CHD risk in HIV infected drug users. PMID:18568100

  5. Technology transfer through performance management: the effects of graphical feedback and positive reinforcement on drug treatment counselors' behavior.

    PubMed

    Andrzejewski, M E; Kirby, K C; Morral, A R; Iguchi, M Y

    2001-07-01

    After drug treatment counselors at a community-based methadone treatment clinic were trained in implementing a contingency management (CM) intervention, baseline measures of performance revealed that, on average, counselors were meeting the performance criteria specified by the treatment protocol about 42% of the time. Counselors were exposed to graphical feedback and a drawing for cash prizes in an additive within-subjects design to assess the effectiveness of these interventions in improving protocol adherence. Counselor performance measures increased to 71% during the graphical feedback condition, and to 81% during the drawing. Each counselor's performance improved during the intervention conditions. Additional analyses suggested that counselors did not have skill deficits that hindered implementation. Rather, protocol implementation occurred more frequently when consequences were added, thereby increasing the overall proportion of criteria met. Generalizations, however, may be limited due to a small sample size and possible confounding of time and intervention effects. Nonetheless, present results show promise that feedback and positive reinforcement could be used to improve technology transfer of behavioral interventions into community clinic settings. PMID:11376922

  6. A Longitudinal Study of Sexual Risk Behavior Among the Adolescent Children of HIV-Positive and HIV-Negative Drug-abusing Fathers

    PubMed Central

    Brook, David W.; Brook, Judith S.; Rubenstone, Elizabeth; Zhang, Chenshu; Finch, Stephen J.

    2013-01-01

    Purpose This is a longitudinal study of the precursors of sexual risk behavior among a cohort of adolescent children of HIV-positive and HIV-negative drug-abusing or drug-dependent fathers. Methods Individual structured interviews were administered to 296 drug-abusing fathers, 43% of whom were HIV-positive, and an adolescent child of each father (X̄ age=16.3 years; SD=2.8). Adolescents were re-interviewed approximately one year later, at Time 2. Results Structural equation modeling showed multiple direct and indirect pathways from psychosocial factors to adolescent sexual risk behavior (sexually active, number of sexual partners, and frequency of condom use). Greater paternal drug addiction and infection with HIV/AIDS, and the youth’s perception of environmental hostility (discrimination and victimization), were both related to increased adolescent maladjustment and substance use. Greater paternal drug addiction and infection with HIV/AIDS also were associated with a weaker father-child mutual attachment, which was linked with increased adolescent maladjustment and substance use. Greater perceived environmental hostility (discrimination and victimization), a weak father-child relationship, and greater adolescent maladjustment and substance use had direct pathways to adolescent sexual risk behavior. Conclusions Findings suggest complex interrelationships among paternal, environmental, social, personal and substance use factors as longitudinal predictors of sexual risk behavior in children whose fathers abuse or are dependent upon drugs. The importance of perceived environmental hostility, the father-child relationship, and adolescent maladjustment and substance use may have implications for public policy as well as prevention and treatment programs. PMID:20159498

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

    PubMed

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

    2014-01-01

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

  8. Using Positive Youth Development Constructs to Design a Drug Education Curriculum for Junior Secondary Students in Hong Kong

    PubMed Central

    Lam, Ching Man; Lau, Patrick S. Y.; Law, Ben M. F.; Poon, Y. H.

    2011-01-01

    This paper outlines the design of a new curriculum for positive youth development (P.A.T.H.S. II) in Hong Kong. The paper discusses the conceptual base for designing a drug-education curriculum for junior-secondary students using four positive youth development constructs—cognitive competence, emotional competence, beliefs in the future, and self-efficacy. The program design is premised on the belief that adolescents do have developmental assets; therefore, the curriculum is designed to develop their psychosocial competencies. The goal of the curriculum is to develop the selfhood of these youths and ultimately achieve the goal of successful adolescent development. PMID:22194667

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

    PubMed

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

    2015-02-01

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

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

    SciTech Connect

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

    2013-10-15

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

  11. Positively charged polymeric nanoparticle reservoirs of terbinafine hydrochloride: preclinical implications for controlled drug delivery in the aqueous humor of rabbits.

    PubMed

    Tayel, Saadia Ahmed; El-Nabarawi, Mohamed Ahmed; Tadros, Mina Ibrahim; Abd-Elsalam, Wessam Hamdy

    2013-06-01

    Frequent instillation of terbinafine hydrochloride (T HCl) eye drops (0.25%, w/v) is necessary to maintain effective aqueous humor concentrations for treatment of fungal keratitis. The current approach aimed at developing potential positively charged controlled-release polymeric nanoparticles (NPs) of T HCl. The estimation of the drug pharmacokinetics in the aqueous humor following ocular instillation of the best-achieved NPs in rabbits was another goal. Eighteen drug-loaded (0.50%, w/v) formulae were fabricated by the nanopreciptation method using Eudragit® RS100 and chitosan (0.25%, 0.5%, and 1%, w/v). Soybean lecithin (1%, w/v) and Pluronic® F68 (0.5%, 1%, and 1.5%, w/v) were incorporated in the alcoholic and aqueous phases, respectively. The NPs were evaluated for particle size, zeta potential, entrapment efficiency percentage (EE%), morphological examination, drug release in simulated tear fluid (pH 7.4), Fourier-transform IR (FT-IR), X-ray diffraction (XRD), physical stability (2 months, 4°C and 25°C), and drug pharmacokinetics in the rabbit aqueous humor relative to an oily drug solution. Spherical, discrete NPs were successfully developed with mean particle size and zeta potential ranging from 73.29 to 320.15 nm and +20.51 to +40.32 mV, respectively. Higher EE% were achieved with Eudragit® RS100-based NPs. The duration of drug release was extended to more than 8 h. FT-IR and XRD revealed compatibility between inactive formulation ingredients and T HCl and permanence of the latter's crystallinity, respectively. The NPs were physically stable, for at least 2 months, when refrigerated. F5-NP suspension significantly (P<0.05) increased drug mean residence time and improved its ocular bioavailability; 1.657-fold. PMID:23615773

  12. Towards Gram-positive antivirulence drugs: new inhibitors of Streptococcus agalactiae Stk1.

    PubMed

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

    2010-06-15

    A structure-activity relationship study from a screening hit and structure-based design strategy has led to the identification of bisarylureas as potent inhibitors of Streptococcus agalactiae Stk1. As this target has been directly linked to bacterial virulence, these inhibitors can be considered as a promising step towards antivirulence drugs. PMID:20529681

  13. Factors associated with positive HIV serostatus among women who use drugs: continued evidence for expanding factors of influence.

    PubMed Central

    Theall, Katherine P.; Sterk, Claire E.; Elifson, Kirk W.; Kidder, Daniel

    2003-01-01

    OBJECTIVE: To identify risk factors associated with positive HIV serostatus among African American women who smoke crack and/or inject drugs and who are not enrolled in drug treatment or another institutional setting. METHODS: Baseline interviews were conducted from June 1998 to June 2000 with 379 heterosexually active women (ages 18 to 59) who had been recruited for potential enrollment into an HIV intervention trial. RESULTS: Adjusted for age and drug using status, women who expressed more difficulty saying no to sex with male partners were more likely to be HIV-positive (adjusted odds ratio [aOR]=3.08, 95% confidence interval [CI] 2.02, 4.83). Similarly, those who indicated greater communication with casual sex partner(s) were less likely to test positive (aOR=0.29, 95% CI 0.10, 0.89). Lower HIV internal control and a history of cuts or burns on lips due to crack smoking were also associated with positive serostatus, and were important confounders in the final multivariate model. A higher level of internal control was associated with a decreased likelihood of positive serostatus, while a history of cuts or burns on the lips was associated with an increased likelihood of HIV antibodies, even after controlling for the amount of oral sex. CONCLUSIONS: A broad array of factors may promote or avert infection with HIV. The degree to which personal attributes and beliefs, and relationship characteristics contribute to the likelihood of infection must continue to be addressed. The importance of oral sex and presence of oral sores and their potential role in transmission was suggested. PMID:12941854

  14. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development.

    PubMed

    Singh, J C; Jhaveri, K; Esteva, F J

    2014-11-11

    Effective targeting of the human epidermal growth factor receptor 2 (HER2) has changed the natural history of HER2 overexpressing (HER2+) metastatic breast cancer. The initial success of trastuzumab improving time to progression and survival rates led to the clinical development of pertuzumab, ado-trastuzumab emtansine and lapatinib. These biologic therapies represent significant additions to the breast medical oncology armamentarium. However, drug resistance ultimately develops and most tumours progress within 1 year. Ongoing studies are evaluating novel therapeutic approaches to overcome primary and secondary drug resistance in tumours, including inhibition of PI3K/TOR, HSP90, IGF-IR and angiogenesis. Mounting experimental data support the clinical testing of immune checkpoint modulators and vaccines. The central nervous system remains a sanctuary site for HER2+ breast cancer and further studies are needed for the prevention and treatment of brain metastases in this population. Despite efforts to identify predictors of preferential benefit from HER2-targeted therapies (e.g., truncated HER2, PTEN loss and SRC activation), HER2 protein overexpression and/or gene amplification remains the most important predictive factor of response to HER2-targeted therapies. In this article, we review the optimal sequence of HER2-targeted therapies and describe ongoing efforts to improve the outcome of HER2+ advanced breast cancer through rational drug development. PMID:25025958

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Possible role of more positive social behaviour in the clinical effect of antidepressant drugs

    PubMed Central

    Young, Simon N.; Moskowitz, Debbie S.; Rot, Marije aan het

    2014-01-01

    Increasing serotonin decreases quarrelsome behaviours and enhances agreeable behaviours in humans. Antidepressants, even those whose primary action is not on serotonin, seem to increase serotonin function. We suggest that antidepressants act in part by effects on social behaviour, which leads to a gradual improvement in mood. We review the evidence supporting the idea that anti-depressants may be moving behaviour from quarrelsome to agreeable. The more positive social responses of interaction partners would initiate a cycle of more positive social behaviour, and this iterative process would result in a clinically significant improvement in mood. PMID:24280182

  2. 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)

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

    2014-05-01

    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.

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

    SciTech Connect

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

    1994-06-01

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

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

    PubMed Central

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

    2015-01-01

    Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5–25 kg/m2), underweight (anorexia nervosa, BMI < 17.5 kg/m2) and overweight (obesity with BMI 30–40, 40–50 and >50 kg/m2, n = 14–15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6 ± 0.3 kg/m2, n = 43). Lastly, in a population of obese patients (BMI 48.5 ± 0.9 kg/m2, n = 85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r = 0.26, p = 0.03) in the population of patients with broad range of BMI (9–85 kg/m2, n = 74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p > 0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r = −0.30, p = 0.008), while no associations were observed with other psychometric eating behavior-related parameters (p > 0.05) in obese patients. In conclusion, these data may point toward a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating. PMID:26089773

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

    PubMed

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

    2015-01-01

    Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5-25 kg/m(2)), underweight (anorexia nervosa, BMI < 17.5 kg/m(2)) and overweight (obesity with BMI 30-40, 40-50 and >50 kg/m(2), n = 14-15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6 ± 0.3 kg/m(2), n = 43). Lastly, in a population of obese patients (BMI 48.5 ± 0.9 kg/m(2), n = 85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r = 0.26, p = 0.03) in the population of patients with broad range of BMI (9-85 kg/m(2), n = 74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p > 0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r = -0.30, p = 0.008), while no associations were observed with other psychometric eating behavior-related parameters (p > 0.05) in obese patients. In conclusion, these data may point toward a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating. PMID:26089773

  6. Syndemic vulnerability, sexual and injection risk behaviors, and HIV continuum of care outcomes in HIV-positive injection drug users

    PubMed Central

    Mizuno, Yuko; Purcell, David W.; Knowlton, Amy R.; Wilkinson, James D.; Gourevitch, Marc N.; Knight, Kelly R.

    2015-01-01

    Limited investigations have been conducted on syndemics and HIV continuum of care outcomes. Using baseline data from a multi-site, randomized controlled study of HIV-positive injection drug users (n=1052), we examined whether psychosocial factors co-occurred, and whether these factors were additively associated with behavioral and HIV continuum of care outcomes. Experiencing one type of psychosocial problem was significantly (p<0.05) associated with an increased odds of experiencing another type of problem. Persons with 3 or more psychosocial problems were significantly more likely to report sexual and injection risk behaviors and were less likely to be adherent to HIV medications. Persons with 4 or more problems were less likely to be virally suppressed. Reporting any problems was associated with not currently taking HIV medications. Our findings highlight the association of syndemics not only with risk behaviors, but also with outcomes related to the continuum of care for HIV-positive persons. PMID:25249392

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

    PubMed

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

    2007-10-01

    The purpose of this study was twofold. First, pretreatment correlations are presented among impulsivity, intoxicant use, HIV risk behavior, spirituality, and motivation in a sample of 38 HIV-positive drug users. Second, treatment outcomes are presented from a preliminary study of spiritual self-schema (3-S(+)) therapy - a manual-guided psychotherapy integrating cognitive and Buddhist psychologies - for increasing motivation for abstinence, HIV prevention, and medication adherence. Impulsivity was negatively correlated with spiritual practices and motivation for recovery, and was positively related to intoxicant use and HIV risk behavior. Relative to a standard care comparison condition, patients completing 3-S(+) therapy reported greater decreases in impulsivity and intoxicant use, and greater increases in spiritual practices and motivation for abstinence, HIV prevention, and medication adherence. PMID:17828761

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

    PubMed

    Neale, Joanne; Stevenson, Caral

    2014-10-01

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

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

    PubMed

    Gujral, B B

    1983-01-01

    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

  10. Penetration into tissues of various drugs active against gram-positive bacteria.

    PubMed

    Kropec, A; Daschner, F D

    1991-04-01

    Gram-positive bacteria are the most important pathogens causing hospital- and community-acquired infections. We therefore reviewed the penetration of various antibiotics active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus into tissues, where staphylococcal infections are common. Rifampicin reaches heart valve concentrations of 65% of the simultaneous serum levels. At 8 h after administration blood and tissues concentrations of rifampicin exceeded the MIC90 values for S. aureus as well as for S. epidermidis. After a 2-g intravenous bolus injection of flucloxacillin heart valve concentrations exceeded MIC values for staphylococci for more than 8 h whereas subcutaneous and muscle concentrations declined within the same time to undetectable levels. The MIC90 values of vancomycin for S. epidermidis and Enterococcus faecalis are 2.0 and 4.0 mg/l respectively and for S. aureus 1.0 mg/l. This concentration is reached in subcutaneous tissue, heart valves and muscle for at least 4-6 h after administration of 15 mg/kg, however the corresponding value for Enterococcus faecalis in heart valve is maintained only for 3-4 h. After two and three dose regimens of teicoplanin serum and bone levels were significantly higher than fat levels, exceeding the MIC90 values for S. aureus, S. epidermidis and E. faecalis. The ratio of tissue concentration of teicoplanin to serum concentrations was 11% for fat and 65% for bone. PMID:2055819

  11. Emergence of cocaine and methamphetamine injection among HIV-positive injection drug users in Northern and Western India

    PubMed Central

    Mehta, Shruti H.; Srikrishnan, Aylur K; Noble, Eva; Vasudevan, Canjeevaram K; Solomon, Suniti; Kumar, M Suresh; Solomon, Sunil S

    2014-01-01

    Background Little is known regarding the epidemiology of drug injection and risk behaviors among injection drug users (IDUs) across India. In particular, there is limited data on the prevalence of stimulant injection. Methods We sampled 801 HIV positive IDUs from 14 locations throughout India to represent the geography of India as well as the diversity in IDU epidemic stage (established epidemics, emerging epidemics and large cities). All participants underwent a behavioral survey and blood draw. Given prior associations with stimulant injection and HIV risk, we compared stimulant injectors (cocaine and/or methamphetamine) to those who injected opiates and/or pharmaceuticals only. Results The median age was 33; 86% were male. The primary drugs injected were heroin, buprenorphine and other pharmaceuticals. In all but four sites, >50% of those actively injecting reported needle sharing. Stimulant injection was most common in emerging epidemics. Compared to exclusive opiate injectors, stimulant injectors were significantly younger, more likely to be educated and employed, more likely to report non-injection use of heroin, crack/cocaine and amphetamines, heavy alcohol use, recent needle sharing (71% vs. 57%), sex with a casual partner (57% vs. 31%) and men having sex with other men (33% vs. 9%; p<0.01 for all). Conclusions Emerging IDU epidemics have a drug/sexual risk profile not previously been observed in India. Given the high prevalence of stimulant injection in these populations, HIV prevention/treatment programs may need to be redesigned to maximize effectiveness. The high levels of injection sharing overall reinforce the need to ensure access to harm-reduction services for all. PMID:24382362

  12. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

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

    PubMed

    Agabio, Roberta; Colombo, Giancarlo

    2015-01-01

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

  14. The administration of nasal drops in the "Kaiteki" position allows for delivery of the drug to the olfactory cleft: a pilot study in healthy subjects.

    PubMed

    Mori, Eri; Merkonidis, Christos; Cuevas, Mandy; Gudziol, Volker; Matsuwaki, Yoshinori; Hummel, Thomas

    2016-04-01

    Systemic treatment with corticosteroids shows therapeutic effects, few patients benefit from intranasal topical drug application, probably due to limited access of the drug to the olfactory epithelium. The aim of the present study was to investigate how drops distribute within the nasal cavity when the "Kaiteki" position is performed. Thirteen healthy volunteers participated. Subjects were lying on the side with the head tilted and the chin turned upward. Blue liquid was used to visualize the intranasal distribution of the nasal drops. The investigation was carried out using photo documentation thorough nasal endoscopy; the intranasal distribution of the dye was judged by two independent observers in both a decongested state and a natural state where no decongestants had been used. With regard to the main criterion of this study, using the "Kaiteki" position, nasal drops reached the olfactory cleft in 96 % of the decongested cases and 75 % of the cases who had not been decongested. However, this difference was not statistically different. Because the "Kaiteki" maneuver is not too difficult to perform, it is more likely that topical steroids can be helpful in cases of olfactory loss. PMID:26141752

  15. [Antimicrobial activity of several drugs against extended-spectrum beta-lactamase positive Enterobacteriaceae isolates in Gifu and Aichi prefecture].

    PubMed

    Nakagawa, Satoshi; Hisada, Harumi; Nomura, Nobuhiko; Mitsuyama, Junichi; Matsubara, Shigenori; Yamaoka, Kazukiyo; Watanabe, Kunitomo; Asano, Yuko; Suematsu, Hiroyuki; Sawamura, Haruki; Hashido, Hikonori; Yamagishi, Yuka; Mikamo, Hiroshige; Matsukawa, Yoko

    2013-10-01

    We investigated the antimicrobial activity of several drugs against 131 extended-spectrum beta-lactamase (ESBL) positive clinical isolates in Gifu and Aichi prefecture from 2007 to 2011. Meropenem (MEPM) and doripenem (DRPM) gave the lowest MIC50 at 0.0313 microg/mL. MEPM gave the lowest MIC90 at 0.0625 microg/mL. According to the Clinical and Laboratory Standards Institute breakpoints, the susceptible rates of carbapenems, tazobactam/piperacillin (TAZ/PIPC) and cefmetazole (CMZ) were higher than 90%. The susceptible rates of MEPM, DRPM, imipenem (IPM), TAZ/PIPC and CMZ were 98.5%, 98.5%, 94.7%, 94.7% and 92.4%. We used the PCR method and identified the molecular types of the ESBL positive isolates. Seventy-two strains had CTX-M-9 group gene and CTX-M-9 group gene is the most frequently detected. Against the CTX-M-9 group gene harboring strains which were the most common in our investigation, the susceptible rates of TAZ/PIPC, MEPM, DRPM and IPM were 100%. It is suggested that not only carbapenems but also TAZ/PIPC and CMZ are useful against infections caused by ESBL positive isolates. PMID:24527516

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

    NASA Astrophysics Data System (ADS)

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

    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.

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

    PubMed

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

    2015-01-01

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

  18. Mutation at positively selected positions in the binding site for HLA-C shows that KIR2DL1 is a more refined but less adaptable NK cell receptor than KIR2DL3.

    PubMed

    Hilton, Hugo G; Vago, Luca; Older Aguilar, Anastazia M; Moesta, Achim K; Graef, Thorsten; Abi-Rached, Laurent; Norman, Paul J; Guethlein, Lisbeth A; Fleischhauer, Katharina; Parham, Peter

    2012-08-01

    Through recognition of HLA class I, killer cell Ig-like receptors (KIR) modulate NK cell functions in human immunity and reproduction. Although a minority of HLA-A and -B allotypes are KIR ligands, HLA-C allotypes dominate this regulation, because they all carry either the C1 epitope recognized by KIR2DL2/3 or the C2 epitope recognized by KIR2DL1. The C1 epitope and C1-specific KIR evolved first, followed several million years later by the C2 epitope and C2-specific KIR. Strong, varying selection pressure on NK cell functions drove the diversification and divergence of hominid KIR, with six positions in the HLA class I binding site of KIR being targets for positive diversifying selection. Introducing each naturally occurring residue at these positions into KIR2DL1 and KIR2DL3 produced 38 point mutants that were tested for binding to 95 HLA- A, -B, and -C allotypes. Modulating specificity for HLA-C is position 44, whereas positions 71 and 131 control cross-reactivity with HLA-A*11:02. Dominating avidity modulation is position 70, with lesser contributions from positions 68 and 182. KIR2DL3 has lower avidity and broader specificity than KIR2DL1. Mutation could increase the avidity and change the specificity of KIR2DL3, whereas KIR2DL1 specificity was resistant to mutation, and its avidity could only be lowered. The contrasting inflexibility of KIR2DL1 and adaptability of KIR2DL3 fit with C2-specific KIR having evolved from C1-specific KIR, and not vice versa. Substitutions restricted to activating KIR all reduced the avidity of KIR2DL1 and KIR2DL3, further evidence that activating KIR function often becomes subject to selective attenuation. PMID:22772445

  19. 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

    PubMed

    Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

    2016-03-15

    4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. PMID:26867486

  20. Analysis with Support Vector Machine Shows HIV-Positive Subjects without Infectious Retinitis Have mfERG Deficiencies Compared to Normal Eyes

    PubMed Central

    Goldbaum, Michael H.; Falkenstein, Irina; Kozak, Igor; Hao, Jiucang; Bartsch, Dirk-Uwe; Sejnowski, Terrance; Freeman, William R.

    2008-01-01

    Purpose To test the following hypotheses: (1) eyes from individuals with human immunodeficiency virus (HIV) have electrophysiologic abnormalities that manifest as multifocal electroretinogram (mfERG) abnormalities; (2) the retinal effects of HIV in immune-competent HIV individuals differ from the effects in immune-incompetent HIV individuals; (3) strong machine learning classifiers (MLCs), like support vector machine (SVM), can learn to use mfERG abnormalities in the second-order kernel (SOK) to distinguish HIV from normal eyes; and (4) the mfERG abnormalities fall into patterns that can be discerned by MLCs. We applied a supervised MLC, SVM, to determine if mfERGs in eyes from patients with HIV differ from mfERGs in HIV-negative controls. Methods Ninety-nine HIV-positive patients without visible retinopathy were divided into 2 groups: (1) 59 high-CD4 individuals (H, 104 eyes), 48.5 ± 7.7 years, whose CD4 counts were never observed below 100, and (2) 40 low-CD4 individuals (L, 61 eyes), 46.2 ± 5.6 years, whose CD4 counts were below 100 for at least 6 months. The normal group (N, 82 eyes) had 41 age-matched HIV-negative individuals, 46.8 ± 6.2 years. The amplitude and latency of the first positive curve (P1, hereafter referred to as a) and the first negative curve (N1, referred to as b) in the SOK of 103 hexagon patterns of the central 28° of the retina were recorded from the eyes in each group. SVM was trained and tested with cross-validation to distinguish H from N and L from N. SOK was chosen as a presumed detector of inner retinal abnormalities. Classifier performance was measured with the area under the receiver operating characteristic (AUROC) curve to permit comparison of MLCs. Improvement in performance and identification of subsets of the most important features were sought with feature selection by backward elimination. Results In general, the SOK b-parameters separated L from N and H from N better than a-parameters, and latency separated L from N and H from N better than amplitude. In the HIV groups, on average, amplitude was diminished and latency was extended. The parameter that most consistently separated L from N and H from N was b-latency. With b-latency, SVM learned to distinguish L from N (AUROC = 0.7.30 ± 0.044, P = .001 against chance [0.500 ± 0.051]) and H from N (0.732 ± 0.038, P = .0001 against chance) equally well. With best-performing subsets (21 out of 103 hexagons) derived by backward elimination, SVM distinguished L from N (0.869 ± 0.030, P < .00005 against chance) and H from N (0.859 ± 0.029, P <.00005 against chance) better than SVM with the full set of hexagons. Mapping the top 10 hexagon locations for L vs N and H vs N produced no apparent pattern. Conclusions This study confirms that mfERG SOK abnormalities develop in the retina of HIV-positive individuals. The new finding of equal severity of b-latency abnormalities in the low- and high-CD4 groups indicates that good immune status under highly active antiretroviral therapy may not protect against retinal damage and, by extension, damage elsewhere. SOKs are difficult for human experts to interpret. Machine learning classifiers, such as SVM, learn from the data without human intervention, reducing the need to rely on human skills to interpret this test. PMID:19277235

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

    PubMed Central

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

    2013-01-01

    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

  2. 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)

    Ikuzawa, Masayuki; Akiduki, Saori; Asashima, Makoto

    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.

  3. Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration.

    PubMed

    Yokota, Osamu; Tsuchiya, Kuniaki; Oda, Tatsurou; Ishihara, Takeshi; de Silva, Rohan; Lees, Andrew J; Arai, Tetsuaki; Uchihara, Toshiki; Ishizu, Hideki; Kuroda, Shigetoshi; Akiyama, Haruhiko

    2006-11-01

    We report the case of a 54-year-old woman with mental retardation who developed frontotemporal dementia and amyotrophic lateral sclerosis (ALS) in the presenium. She presented with dementia at age 48, and motor neuron signs developed at age 53. She had no family history of dementia or ALS. Postmortem examination disclosed histopathological features of ALS, including pyramidal tract degeneration, mild loss of motor neurons, and many Bunina bodies immunoreactive for cystatin C, but not ubiquitin-positive inclusions. Unusual features of this case included severe neuronal loss in the substantia nigra and medial globus pallidus. The subthalamic nucleus, limbic system, and cerebral cortex were well preserved. In addition, neurofibrillary tangles (NFTs) were found in the frontal, temporal, insular, and cingulate cortices, nucleus basalis of Meynert, and locus coeruleus, and to a lesser degree, in the dentate nucleus, cerebellum, hippocampus, and amygdala. No ballooned neurons, tufted astrocytes, or astrocytic plaques were found. Tau immunostaining demonstrated many pretangles rather than NFTs and glial lesions resembling astrocytic plaques in the frontal and temporal cortices. This glial tau pathology predominantly developed in the middle to deep layers in the primary motor cortex, and was frequently associated with the walls of blood vessels. NFTs were immunolabeled with 3-repeat and 4-repeat specific antibodies against tau, respectively. Although the pathophysiological relationship between tau pathology and the selective involvement of motor neurons, substantia nigra, and globus pallidus was unclear, we considered that it might be more than coincidental. PMID:17021751

  4. Computerized Definitions Showed High Positive Predictive Values for Identifying Hospitalizations for Congestive Heart Failure and Selected Infections in Medicaid Enrollees with Rheumatoid Arthritis

    PubMed Central

    Grijalva, Carlos G.; Chung, Cecilia P.; Stein, C. Michael; Gideon, Patricia S.; Dyer, Shannon M.; Mitchel, Edward F.; Griffin, Marie R.

    2016-01-01

    Purpose Computerized definitions are used to identify serious infections and congestive heart failure leading to hospitalizations in studies of medication safety. However, information on their accuracy is limited. We evaluated the ability of computerized definitions to identify these conditions as the reason for admission among patients diagnosed with rheumatoid arthritis. Methods Medical charts were randomly selected from a systematic sample of hospitalizations for selected conditions in a cohort of Medicaid patients with rheumatoid arthritis. We calculated positive predictive values (PPV) for computerized definitions for community-acquired pneumonia, invasive pneumococcal disease, sepsis, opportunistic mycoses and congestive heart failure using charts reviews as gold standard and computed inter-reviewer agreement statistics. Results From 2667 hospitalizations, 336 (13%) records were selected for review. A total of 277 charts (83%) were available. Based on any discharge diagnosis, PPVs for hospitalizations due to community-acquired pneumonia, invasive pneumococcal disease, sepsis and opportunistic mycoses were 84%, 100%, 80% and 62%, respectively. Restricting definitions to principal diagnoses yielded higher PPVs, 95% for pneumonia and 100% for other diagnoses. The PPV of a principal diagnosis for congestive heart failure was 100%. Inter-reviewer agreement was at least 77% for all outcomes. Conclusion These findings suggest that computerized definitions can identify congestive heart failure and selected infections leading to hospitalization in Medicaid patients with rheumatoid arthritis. PMID:18543352

  5. 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

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

    2014-07-01

    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

  6. The Perioperative Surgical Home (PSH): A Comprehensive Review of US and Non-US Studies Shows Predominantly Positive Quality and Cost Outcomes

    PubMed Central

    Kash, Bita A; Zhang, Yichen; Cline, Kayla M; Menser, Terri; Miller, Thomas R

    2014-01-01

    Context The evolving concept of more rigorously coordinated and integrated perioperative management, often referred to as the perioperative surgical home (PSH), parallels the well-known concept of a patient-centered medical home (PCMH), as they share a vision of improved clinical outcomes and reductions in cost of care through patient engagement and care coordination. Elements of the PSH and similar surgical care coordination models have been studied in the United States and other countries. Methods This comprehensive review of peer-reviewed literature investigates the history and evolution of PSH and PSH-like models and summarizes the results of studies of PSH elements in the United States and in other countries. We reviewed more than 250 potentially relevant studies. At the conclusion of the selection process, our search had yielded a total of 152 peer-reviewed articles published between 1980 and 2013. Findings The literature reports consistent and significant positive findings related to PSH initiatives. Both US and non-US studies stress the role of anesthesiologists in perioperative patient management. The PSH may have the greatest impact on preparing patients for surgery and ensuring their safe and effective transition to home or other postoperative rehabilitation. There appear to be some subtle differences between US and non-US research on the PSH. The literature in non-US settings seems to focus strictly on the comparison of outcomes from changing policies or practices, whereas US research seems to be more focused on the discovery of innovative practice models and other less direct changes, for example, information technology, that may be contributing to the evolution toward the PSH model. Conclusions The PSH model may have significant implications for policymakers, payers, administrators, clinicians, and patients. The potential for policy-relevant cost savings and quality improvement is apparent across the perioperative continuum of care, especially for integrated care organizations, bundled payment, and value-based purchasing. PMID:25492605

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

    PubMed Central

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

    2014-01-01

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

  8. Combination of pedCAT(®) for 3D Imaging in Standing Position With Pedography Shows No Statistical Correlation of Bone Position With Force/Pressure Distribution.

    PubMed

    Richter, Martinus; Zech, Stefan; Hahn, Sarah; Naef, Issam; Merschin, David

    2016-01-01

    pedCAT(®) (CurveBeam, Warrington, PA) is a technology for 3-dimensional (3D) imaging with full weightbearing that has been proved to exactly visualize the 3D bone position. For the present study, a customized pedography sensor (Pliance; Novel, Munich, Germany) was inserted into the pedCAT(®). The aim of our study was to analyze the correlation of the bone position and force/pressure distribution. A prospective consecutive study of 50 patients was performed, starting July 28, 2014. All patients underwent a pedCAT(®) scan and simultaneous pedography with full weightbearing in the standing position. The following parameters were measured on the pedCAT(®) image for the right foot by 3 different investigators 3 times: lateral talo-first metatarsal angle, calcaneal pitch angle, and minimum height of the fifth metatarsal base, second to fifth metatarsal heads, and medial sesamoid. From the pedography data, the following parameters were defined using the standardized software algorithm: midfoot contact area, maximum force of midfoot, maximum force of midfoot lateral, maximum force of entire foot, and maximum pressure of first to fifth metatarsal. The values of the corresponding pedCAT(®) and pedographic parameters were correlated (Pearson). The intra- and interobserver reliability of the pedCAT(®) measurements were sufficient (analysis of variance, p > .8 for each, power >0.8). No sufficient correlation was found between the pedCAT(®) and pedographic parameters (r < 0.05 or r > -0.38).3D bone position did not correlate with the force and pressure distribution under the foot sole during simultaneous pedCAT(®) scanning and pedography. Thus, the bone positions measured with pedCAT(®) do not allow conclusions about the force and pressure distribution. However, the static pedographic parameters also do not allow conclusions about the 3D bone position.one position and force/pressure distribution are important parameters for diagnostics, planning, and follow-up examinations in foot and ankle surgery. PMID:26915685

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

    PubMed Central

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

    2012-01-01

    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

  10. Surface modification with multiphilic ligands at detectable well defined active positions of nano-object of giant wheel shaped molybdenum blue showing third-order nonlinear optical properties

    NASA Astrophysics Data System (ADS)

    Zhang, Lijuan; Li, Yuhao; Zhou, Yunshan

    2010-04-01

    The reaction of an aqueous solution of sodium molybdate with L-tyrosine in the presence of reducing agent results in the formation of a new compound of the formula of Na 8Co 3[Mo VI126 Mo V28O 462H 14(H 2O) 46(HOC 6H 4CH 2CH( NH3+)COO -) 12]·ca. 200H 2O. The compound contains nanosized ring-shaped clusters with tyrosine ligands possessing different types of functional groups (one -CO 2, one -NH3+ and one -ArOH) coordinated through the carboxylate groups at the active sites of the inner cavity. Importantly, the result demonstrates that not only active sites/areas of the cluster surface under a specified condition can be directly monitored and detected but also novel type surfaces within the cavity of a nano-structured ring-shaped cluster can be generated simultaneously. The nonlinear optical properties of the new cluster are studied using the well-known Z-scan technique at a wavelength of 532 nm with laser pulse duration of 18 ps. The results show that the new cluster exhibits interesting self-focusing nonlinear optical response with the real and imaginary parts of the third-order nonlinear optical susceptibility χ(3) being 1.069 × 10 -13(esu) and 2.529 × 10 -15(esu), respectively, which may find application in material science.

  11. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

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

  12. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

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

  13. Concentrations of alprazolam in blood from impaired drivers and forensic autopsies were not much different but showed a high prevalence of co-ingested illicit drugs.

    PubMed

    Jones, Alan Wayne; Holmgren, Anita

    2013-03-01

    Alprazolam is a benzodiazepine anxiolytic widely prescribed for treatment of panic-disorder and social phobias, although this medication is also subject to abuse. In this paper, the concentrations of alprazolam in venous blood samples from impaired drivers were compared with femoral blood samples from forensic autopsies classified as intoxication or other causes of death (e.g. natural, trauma). After liquid-liquid extraction (n-butyl acetate) alprazolam was determined in blood by capillary gas chromatography with a nitrogen-phosphorous detector. The mean (median) and range of alprazolam concentrations in blood from impaired drivers (n = 773) were 0.08 mg/L (0.05 mg/L) and 0.02-3.9 mg/L, respectively. Many traffic offenders had co-ingested ethanol (13%), amphetamine (46%), cannabis (32%), or heroin (14%), as well as other drugs. In deaths attributed to drug intoxication, the mean (median) and range of alprazolam concentrations in blood (n = 438) were 0.10 mg/L (0.06 mg/L) and 0.02-1.6 mg/L, respectively, which were not much different from other causes of death (n = 278); 0.08 mg/L (0.05 mg/L) and 0.02-0.9 mg/L. Median concentrations of alprazolam in blood from living and deceased persons did not seem to depend on the number of co-ingested substances. The result of this pharmacoepidemiological study suggests that alprazolam is a fairly innocent drug when used as monotherapy, but toxicity problems arise when co-ingested with illicit drugs and/or psychoactive medication. PMID:23257168

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

    PubMed

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

    2012-10-01

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

  15. HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users

    PubMed Central

    Lai, Alessia; Bozzi, Giorgio; Franzetti, Marco; Binda, Francesca; Simonetti, Francesco R.; De Luca, Andrea; Micheli, Valeria; Meraviglia, Paola; Bagnarelli, Patrizia; Di Biagio, Antonio; Monno, Laura; Saladini, Francesco; Zazzi, Maurizio; Zehender, Gianguglielmo; Ciccozzi, Massimo; Balotta, Claudia

    2016-01-01

    Background Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype. Aim Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches. Results The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8%) clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively) compared to those from Africa (20%) (p < .001). Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056) and in women with respect to men (81.4% vs. 53.2%, p < .006). Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece. Conclusions Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of such variant, probably through sex work. PMID:26752062

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Copeland, Lorraine

    2004-01-01

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

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

    SciTech Connect

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

    2009-05-20

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

  19. Isolation and Structural Elucidation of Brevibacillin, an Antimicrobial Lipopeptide from Brevibacillus laterosporus That Combats Drug-Resistant Gram-Positive Bacteria.

    PubMed

    Yang, Xu; Huang, En; Yuan, Chunhua; Zhang, Liwen; Yousef, Ahmed E

    2016-05-01

    A new environmental bacterial strain exhibited strong antimicrobial characteristics against methicillin-resistantStaphylococcus aureus, vancomycin-resistant strains ofEnterococcus faecalisandLactobacillus plantarum, and other Gram-positive bacteria. The producer strain, designated OSY-I1, was determined to beBrevibacillus laterosporusvia morphological, biochemical, and genetic analyses. The antimicrobial agent was extracted from cells of OSY-I1with isopropanol, purified by high-performance liquid chromatography, and structurally analyzed using mass spectrometry (MS) and nuclear magnetic resonance (NMR). The MS and NMR results, taken together, uncovered a linear lipopeptide consisting of 13 amino acids and an N-terminal C6fatty acid (FA) chain, 2-hydroxy-3-methylpentanoic acid. The lipopeptide (FA-Dhb-Leu-Orn-Ile-Ile-Val-Lys-Val-Val-Lys-Tyr-Leu-valinol, where Dhb is α,β-didehydrobutyric acid and valinol is 2-amino-3-methyl-1-butanol) has a molecular mass of 1,583.0794 Da and contains three modified amino acid residues: α,β-didehydrobutyric acid, ornithine, and valinol. The compound, designated brevibacillin, was determined to be a member of a cationic lipopeptide antibiotic family. In addition to its potency against drug-resistant bacteria, brevibacillin also exhibited low MICs (1 to 8 μg/ml) against selected foodborne pathogenic and spoilage bacteria, such asListeria monocytogenes,Bacillus cereus, andAlicyclobacillus acidoterrestris Purified brevibacillin showed no sign of degradation when it was held at 80°C for 60 min, and it retained at least 50% of its antimicrobial activity when it was held for 22 h under acidic or alkaline conditions. On the basis of these findings, brevibacillin is a potent antimicrobial lipopeptide which is potentially useful to combat drug-resistant bacterial pathogens and foodborne pathogenic and spoilage bacteria. PMID:26921428

  20. The Association of Nurses in AIDS Care. Position paper on harm reduction and HIV care for drug users: integrating harm-reduction methods and HIV care.

    PubMed

    Fisk, S N

    1998-01-01

    As the epidemic of HIV disease continues to grow among drug users and their sexual partners, new ways must be adopted to do prevention work, outreach, and service delivery to this population. The Harm Reduction Model offers methods of working with drug users, which are in contrast to traditional methods based on confrontation and that require abstinence before change can occur. This position paper examines the Harm Reduction Model and outlines areas in which the Association of Nurses in AIDS Care can play a role in the expansion of harm-reduction-based intervention and policies. PMID:9589418

  1. Sexual risk behavior associated with co-administration of methamphetamine and other drugs in a sample of HIV-positive men who have sex with men.

    PubMed

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

    2009-01-01

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

  2. Differences in T cell distribution and CCR5 expression in HIV-positive and HIV-exposed seronegative persons who inject drugs.

    PubMed

    Kallas, Eveli; Huik, Kristi; Türk, Silver; Pauskar, Merit; Jõgeda, Ene-Ly; Šunina, Marina; Karki, Tõnis; Des Jarlais, Don; Uusküla, Anneli; Avi, Radko; Lutsar, Irja

    2016-06-01

    Some individuals remain uninfected despite repeated exposure to HIV. This protection against HIV has been partly associated with altered T cell subset distributions and CCR5 expression levels. However, the majority of studies have been conducted in sexually exposed subjects. We aimed to assess whether HIV infection and intravenous drug use were associated with differences in CCR5 expression, immune activation on the CD4+ and CD8+ T cells and T cell distribution among Caucasian persons who inject drugs (PWIDs). Analyses of the data from 41 HIV-positive PWIDs, 47 HIV-exposed seronegative PWIDs (ESNs) and 47 age- and gender-matched HIV-negative non-drug users are presented. Of all of the study subjects, 111 (82 %) were male, and the median age was 29 years. T cell phenotyping was performed in peripheral blood mononuclear cells with multicolour flow cytometry using anti-CD3, CD4, CD8, CD45RA, CD45RO, HLA-DR and CCR5 antibodies. The ESNs exhibited greater levels of immune activation and higher percentages of CD4+ CD45RA+RO+ and CD8+ CD45RA+RO+ cells compared to the controls but not the HIV-positive people. The CCR5 expression on the CD4+ T cell subsets in the ESNs was lower than that in the controls but similar to that the HIV positives. The percentages of CCR5+ T cells were similar in all study groups and in most of the studied cell populations. Intravenous drug use was similarly associated with differences in T cell subset distributions and CCR5 expression among both the HIV-positive and HIV-negative PWIDs compared with the controls. PMID:26696529

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. The School Team Approach: Preventing Alcohol and Drug Abuse by Creating Positive Environments for Learning and Growth.

    ERIC Educational Resources Information Center

    Pizza, Joan; Resnick, Henry S.

    Alcohol and drug abuse continue to have serious and negative effects on the nation's youth. One response to this problem is described in this monograph on the School Team Program, a national network of training and resource centers set up to train teams of school and community representatives in problem solving techniques that would help them…

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

    PubMed

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

    2013-12-01

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

  7. Expanding access to HIV testing and counseling and exploring vulnerabilities among spouses of HIV-positive men who inject drugs in Pakistan

    PubMed Central

    Shahid, Salman; Majeed, Mohammad Faisal; Awaan, Ahmad Bakhsh; Mirza, Humayun; Sarfraz, Nasir; Veronese, Vanessa

    2016-01-01

    Objectives To explore the utility of home and community-based HIV testing and counseling (HTC) to increase detection of undiagnosed HIV among female spouses and children of HIV-positive PWID in Punjab province, Pakistan. Design Between March 2014 and March 2015, home-based HTC was provided by a local NGO to spouses of HIV-positive PWID in Lahore, Faisalabad, and Sargodha. Convenience sampling was used to identify 2400 married, HIV-positive men who inject drugs and who were currently registered and receiving harm reduction services from the NGO ‘Roshan Rasta’ and seek consent to approach their wives. Method Trained outreach teams conducted HTC and administered a short sociodemographic and behavioral questionnaire to consenting spouses in their homes. HIV-exposed children were also tested with parental consent. Results of the 2400 married HIV positive male-injecting drug users, only 1959 spouses were approached and 1896 agreed to HTC (96.8%). HIV prevalence was 5.3% (n = 101) among spouses and they had very low level of HIV-related knowledge and protective behaviors Conclusion Home and community-based HTC was effective in identifying undiagnosed HIV among spouses of PWID, the majority of whom reported low rates of prior HIV testing and low HIV-related knowledge. Expansion of HIV prevention services and linkages to treatment and care including PMTCT are urgently needed for this group. PMID:26945140

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

    PubMed Central

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

    2015-01-01

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

  9. Diagnostic usefulness of the GenoType MTBDRplus assay for detecting drug-resistant tuberculosis using AFB smear-negative specimens with positive TB-PCR result.

    PubMed

    Lee, Young Seok; Kang, Hye-Rim; Lee, Si-Hyeong; Kim, Yunmi; Kim, Mi-Yeong; Shin, Jeong Hwan; Moon, Jae Young; Lee, Hyun-Kyung; Park, So Young; Mo, Eun-Kyung; Park, Yong Bum; Moon, Soo-Yoon; Oh, Minkyung; Ko, Yousang

    2016-05-01

    Background The aim of this study was to evaluate the diagnostic accuracy of the GenoType MTBDRplus assay in detecting drug-resistant tuberculosis (DR-TB) by using acid-fast bacilli (AFB) smear-negative specimens with positive TB-PCR results. Methods The MTBDRplus assay was performed with 2 different categories of 117 samples, including AFB smear-positive specimens (n = 53) and AFB smear-negative specimens (n = 64), which exhibited positive TB-PCR results, at a single institution. The results were retrospectively compared with the results of the phenotypic drug susceptibility test (DST), for reference. Results A total of 105 tests were finally analyzed. Of these, 54 tests were conducted using AFB smear-negative specimens with positive TB-PCR results. The MTBDRplus assay for these 54 samples demonstrated a sensitivity of 100%, specificity of 98%, positive predictive value (PPV) of 75%, and negative predictive value (NPV) of 100% in detecting rifampicin resistance. With these same species, the sensitivity, specificity, PPV, and NPV values for the MTBDRplus assay were 83.3%, 97.9%, 83.3%, and 97.9%, respectively, for the detection of isoniazid resistance. The overall correlation between the MTBDRplus assay and phenotypic DST demonstrated excellent agreement for detection of rifampicin resistance (κ = 0.847) and for detection of INH resistance (κ = 0.812), respectively. Conclusions The MTBDRplus assay can be used effectively even on AFB smear-negative specimens from TB patients, when the TB-PCR is positive. This result might help clinicians to manage patients with suspected DR-TB in difficult situations. PMID:26654187

  10. Phylogenetic and molecular characterization of a 23S rRNA gene positions the genus Campylobacter in the epsilon subdivision of the Proteobacteria and shows that the presence of transcribed spacers is common in Campylobacter spp.

    PubMed Central

    Trust, T J; Logan, S M; Gustafson, C E; Romaniuk, P J; Kim, N W; Chan, V L; Ragan, M A; Guerry, P; Gutell, R R

    1994-01-01

    The nucleotide sequence of a 23S rRNA gene of Campylobacter coli VC167 was determined. The primary sequence of the C. coli 23S rRNA was deduced, and a secondary-structure model was constructed. Comparison with Escherichia coli 23S rRNA showed a major difference in the C. coli rRNA at approximately position 1170 (E. coli numbering) in the form of an extra sequence block approximately 147 bp long. PCR analysis of 31 other strains of C. coli and C. jejuni showed that 69% carried a transcribed spacer of either ca. 147 or ca. 37 bp. Comparison of all sequenced Campylobacter transcribed spacers showed that the Campylobacter inserts were related in sequence and percent G+C content. All Campylobacter strains carrying transcribed spacers in their 23S rRNA genes produced fragmented 23S rRNAs. Other strains which produced unfragmented 23S rRNAs did not appear to carry transcribed spacers at this position in their 23S rRNA genes. At the 1850 region (E. coli numbering), Campylobacter 23S rRNA displayed a base pairing signature most like that of the beta and gamma subdivisions of the class Proteobacteria, but in the 270 region, Campylobacter 23S rRNA displayed a helix signature which distinguished it from the alpha, beta, and gamma subdivisions. Phylogenetic analysis comparing C. coli VC167 23S rRNA and a C. jejuni TGH9011 (ATCC 43431) 23S rRNA with 53 other completely sequenced (eu)bacterial 23S rRNAs showed that the two campylobacters form a sister group to the alpha, beta, and gamma proteobacterial 23S rRNAs, a positioning consistent with the idea that the genus Campylobacter belongs to the epsilon subdivision of the class Proteobacteria. Images PMID:8045890

  11. Sulfoxides, Analogues of L-Methionine and L-Cysteine As Pro-Drugs against Gram-Positive and Gram-Negative Bacteria.

    PubMed

    Anufrieva, N V; Morozova, E A; Kulikova, V V; Bazhulina, N P; Manukhov, I V; Degtev, D I; Gnuchikh, E Yu; Rodionov, A N; Zavilgelsky, G B; Demidkina, T V

    2015-01-01

    The problem of resistance to antibiotics requires the development of new classes of broad-spectrum antimicrobial drugs. The concept of pro-drugs allows researchers to look for new approaches to obtain effective drugs with improved pharmacokinetic and pharmacodynamic properties. Thiosulfinates, formed enzymatically from amino acid sulfoxides upon crushing cells of genus Allium plants, are known as antimicrobial compounds. The instability and high reactivity of thiosulfinates complicate their use as individual antimicrobial compounds. We propose a pharmacologically complementary pair: an amino acid sulfoxide pro-drug and vitamin B6 - dependent methionine γ-lyase, which metabolizes it in the patient's body. The enzyme catalyzes the γ- and β-elimination reactions of sulfoxides, analogues of L-methionine and L-cysteine, which leads to the formation of thiosulfinates. In the present work, we cloned the enzyme gene from Clostridium sporogenes. Ionic and tautomeric forms of the internal aldimine were determined by lognormal deconvolution of the holoenzyme spectrum and the catalytic parameters of the recombinant enzyme in the γ- and β-elimination reactions of amino acids, and some sulfoxides of amino acids were obtained. For the first time, the possibility of usage of the enzyme for effective conversion of sulfoxides was established and the antimicrobial activity of thiosulfinates against Gram-negative and Gram-positive bacteria in situ was shown. PMID:26798500

  12. Sulfoxides, Analogues of L-Methionine and L-Cysteine As Pro-Drugs against Gram-Positive and Gram-Negative Bacteria

    PubMed Central

    Anufrieva, N. V.; Morozova, E. A.; Kulikova, V. V.; Bazhulina, N. P.; Manukhov, I. V.; Degtev, D. I.; Gnuchikh, E. Yu.; Rodionov, A. N.; Zavilgelsky, G. B.; Demidkina, T. V.

    2015-01-01

    The problem of resistance to antibiotics requires the development of new classes of broad-spectrum antimicrobial drugs. The concept of pro-drugs allows researchers to look for new approaches to obtain effective drugs with improved pharmacokinetic and pharmacodynamic properties. Thiosulfinates, formed enzymatically from amino acid sulfoxides upon crushing cells of genus Allium plants, are known as antimicrobial compounds. The instability and high reactivity of thiosulfinates complicate their use as individual antimicrobial compounds. We propose a pharmacologically complementary pair: an amino acid sulfoxide pro-drug and vitamin B6 – dependent methionine γ-lyase, which metabolizes it in the patient’s body. The enzyme catalyzes the γ- and β-elimination reactions of sulfoxides, analogues of L-methionine and L-cysteine, which leads to the formation of thiosulfinates. In the present work, we cloned the enzyme gene from Clostridium sporogenes. Ionic and tautomeric forms of the internal aldimine were determined by lognormal deconvolution of the holoenzyme spectrum and the catalytic parameters of the recombinant enzyme in the γ- and β-elimination reactions of amino acids, and some sulfoxides of amino acids were obtained. For the first time, the possibility of usage of the enzyme for effective conversion of sulfoxides was established and the antimicrobial activity of thiosulfinates against Gram-negative and Gram-positive bacteria in situ was shown. PMID:26798500

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

    PubMed

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

    2011-09-01

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

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

    PubMed Central

    2011-01-01

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

  15. 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

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

    2014-01-01

    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

  16. 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

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

    2014-01-01

    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

  17. Packed cell volume Platelet count, PT, PTTK and Fibrinogen concentration of HIV positive patients on antiretroviral drugs

    PubMed Central

    Osime, Evarista Odaburhine; Oresanja, Omobolaji Oluwole; Okwara, Benson Uchechukwu

    2015-01-01

    Objective: This is aimed at investigating some coagulation and haematologic profile of HIV positive patients on highly active antiretroviral therapy in patients attending clinic at the University of Benin Teaching Hospital. Methods: This is a correlation study comprising fifty (50) HIV positive patients on HAART between 6 – 12 months as test subjects and fifty (50) HIV positive patients who have not began HAART as control subjects. Five millilitres of blood was withdrawn from each group by venepuncture into ethylene diaminetetracetic and sodium citrate anticoagulant containers. Platelet counts were estimated manually using ammonium oxalate solution, packed cell volume by the microhaematocrit method while Prothrombin Time (PT), Activated partial thrombroplastin time and fibrinogen concentration were done by methods described by Monica Chessbrough. Results: This is presented as mean ± standard error of mean. There were reduction in PCV and platelet count between test and control subjects although not statistically significant (P> 0.05) while there was a significant increase in PT and PTTK between test and control groups (P<0.05). No significant change was observed in fibrinogen concentration in HIV patients on HAART and those not on HAART. Conclusion: HAART increases PT and PTTK in HIV infection. PMID:26870130

  18. Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer.

    PubMed

    Kulhari, Hitesh; Pooja, Deep; Shrivastava, Shweta; Kuncha, Madhusudana; Naidu, V G M; Bansal, Vipul; Sistla, Ramakrishna; Adams, David J

    2016-01-01

    Approximately 20% of breast cancer cases are human epidermal growth factor receptor 2 (HER2)-positive. This type of breast cancer is more aggressive and tends to reoccur more often than HER2-negative breast cancer. In this study, we synthesized trastuzumab (TZ)-grafted dendrimers to improve delivery of docetaxel (DTX) to HER2-positive breast cancer cells. Bioconjugation of TZ on the surface of dendrimers was performed using a heterocrosslinker, MAL-PEG-NHS. For imaging of cancer cells, dendrimers were also conjugated to fluorescein isothiocyanate. Comparative in vitro studies revealed that these targeted dendrimers were more selective, and had higher antiproliferation activity, towards HER2-positive MDA-MB-453 human breast cancer cells than HER2-negative MDA-MB-231 human breast cancer cells. When compared with unconjugated dendrimers, TZ-conjugated dendrimers also displayed higher cellular internalization and induction of apoptosis against MDA-MB-453 cells. Binding of TZ to the dendrimer surface could help site-specific delivery of DTX and reduce systemic toxicity resulting from its lack of specificity. In addition, in vivo studies revealed that the pharmacokinetic profile of DTX was significantly improved by the conjugated nanosystem. PMID:27052896

  19. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus

    PubMed Central

    Handzlik, Jadwiga; Matys, Anna; Kieć-Kononowicz, Katarzyna

    2013-01-01

    The paper focuses on recent achievements in the search for new chemical compounds able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens. An analysis of the results of the search for new efflux pump inhibitors (EPIs) for Gram-positive bacteria, which have been performed over the last decade, indicates that almost all efforts are focused on the NorA (MFS) efflux pump in S. aureus. Considering the chemical structures of the NorA EPIs that have been identified, it can be observed that the most active agents belong to the families of compounds possessing conjugated double bonds, e.g., chalcones, piperine-like compounds, N-cinnamoylphenalkylamides or citral amide derivatives. Indole-, dihydronaphthyl-, 2-chloro-5-bromo-phenyl- or piperidine moieties seem to be profitable for the EPI properties, as well. These results, together with an increasing knowledge about a variety of efflux pumps that are involved in MDR of Gram-positive pathogens underline that further search for new EPIs should pay more attention to develop MDR efflux protein targets, including SMR, MATE, ABC or other members of the MFS family. PMID:27029290

  20. Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer

    PubMed Central

    Kulhari, Hitesh; Pooja, Deep; Shrivastava, Shweta; Kuncha, Madhusudana; Naidu, V. G. M.; Bansal, Vipul; Sistla, Ramakrishna; Adams, David J.

    2016-01-01

    Approximately 20% of breast cancer cases are human epidermal growth factor receptor 2 (HER2)-positive. This type of breast cancer is more aggressive and tends to reoccur more often than HER2-negative breast cancer. In this study, we synthesized trastuzumab (TZ)-grafted dendrimers to improve delivery of docetaxel (DTX) to HER2-positive breast cancer cells. Bioconjugation of TZ on the surface of dendrimers was performed using a heterocrosslinker, MAL-PEG-NHS. For imaging of cancer cells, dendrimers were also conjugated to fluorescein isothiocyanate. Comparative in vitro studies revealed that these targeted dendrimers were more selective, and had higher antiproliferation activity, towards HER2-positive MDA-MB-453 human breast cancer cells than HER2-negative MDA-MB-231 human breast cancer cells. When compared with unconjugated dendrimers, TZ-conjugated dendrimers also displayed higher cellular internalization and induction of apoptosis against MDA-MB-453 cells. Binding of TZ to the dendrimer surface could help site-specific delivery of DTX and reduce systemic toxicity resulting from its lack of specificity. In addition, in vivo studies revealed that the pharmacokinetic profile of DTX was significantly improved by the conjugated nanosystem. PMID:27052896

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

    PubMed Central

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

    2012-01-01

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

  2. 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

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

    2012-07-01

    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

  3. SLC6A14 (ATB0,+) protein, a highly concentrative and broad specific amino acid transporter, is a novel and effective drug target for treatment of estrogen receptor-positive breast cancer.

    PubMed

    Karunakaran, Senthil; Ramachandran, Sabarish; Coothankandaswamy, Veena; Elangovan, Selvakumar; Babu, Ellappan; Periyasamy-Thandavan, Sudharsan; Gurav, Ashish; Gnanaprakasam, Jaya P; Singh, Nagendra; Schoenlein, Patricia V; Prasad, Puttur D; Thangaraju, Muthusamy; Ganapathy, Vadivel

    2011-09-01

    SLC6A14, also known as ATB(0,+), is an amino acid transporter with unique characteristics. It transports 18 of the 20 proteinogenic amino acids. However, this transporter is expressed only at low levels in normal tissues. Here, we show that the transporter is up-regulated specifically in estrogen receptor (ER)-positive breast cancer, demonstrable with primary human breast cancer tissues and human breast cancer cell lines. SLC6A14 is an estrogen/ER target. The transport features of SLC6A14 include concentrative transport of leucine (an activator of mTOR), glutamine (an essential amino acid for nucleotide biosynthesis and substrate for glutaminolysis), and arginine (an essential amino acid for tumor cells), suggesting that ER-positive breast cancer cells up-regulate SLC6A14 to meet their increased demand for these amino acids. Consequently, treatment of ER-positive breast cancer cells in vitro with ?-methyl-DL-tryptophan (?-MT), a selective blocker of SLC6A14, induces amino acid deprivation, inhibits mTOR, and activates autophagy. Prolongation of the treatment with ?-MT causes apoptosis. Addition of an autophagy inhibitor (3-methyladenine) during ?-MT treatment also induces apoptosis. These effects of ?-MT are specific to ER-positive breast cancer cells, which express the transporter. The ability of ?-MT to cause amino acid deprivation is significantly attenuated in MCF-7 cells, an ER-positive breast cancer cell line, when SLC6A14 is silenced with shRNA. In mouse xenograft studies, ?-MT by itself is able to reduce the growth of the ER-positive ZR-75-1 breast cancer cells. These studies identify SLC6A14 as a novel and effective drug target for the treatment of ER-positive breast cancer. PMID:21771784

  4. CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12.

    PubMed

    Mulaw, M A; Krause, A; Krause, A J; Deshpande, A J; Krause, L F; Rouhi, A; La Starza, R; Borkhardt, A; Buske, C; Mecucci, C; Ludwig, W-D; Lottaz, C; Bohlander, S K

    2012-05-01

    The t(10;11)(p12;q14) is a recurring chromosomal translocation that gives rise to the CALM/AF10 fusion gene, which is found in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma. We analyzed the fusion transcripts in 20 new cases of CALM/AF10-positive leukemias, and compared the gene expression profile of 10 of these to 125 patients with other types of leukemia and 10 normal bone marrow samples. Based on gene set enrichment analyses, the CALM/AF10-positive samples showed significant upregulation of genes involved in chromatin assembly and maintenance and DNA repair process, and downregulation of angiogenesis and cell communication genes. Interestingly, we observed a striking upregulation of four genes located immediately centromeric to the break point of the t(10;11)(p12;q14) on 10p12 (COMMD3 (COMM domain containing 3), BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), DNAJC1 (DnaJ (Hsp40) homolog subfamily C member 1) and SPAG6 (sperm associated antigen 6)). We also conducted semiquantitative reverse transcriptase-PCR analysis on leukemic blasts from a murine CALM/AF10 transplantation model that does not have the translocation. Commd3, Bmi1 and Dnajc1, but not Spag6 were upregulated in these samples. These results strongly indicate that the differential regulation of these three genes is not due to the break point effect but as a consequence of the CALM/AF10 fusion gene expression, though the mechanism of regulation is not well understood. PMID:22064352

  5. Improving Monitoring and Reporting of Adverse Drug Reactions (ADRs) in HIV positive patients on Antiretroviral Therapy (ART) in Nigeria

    PubMed Central

    Agu, Kenneth Anene; Oparah, Azuka Cyriacus; Ochei, Uche M.

    2012-01-01

    Under-reporting of ADR may be associated with poor knowledge, attitudes and practices to pharmacovigilance. This study evaluated knowledge, attitudes and practices of healthcare professionals about ADR monitoring and reporting following interventions. This longitudinal study included 36 healthcare professionals participating in ART program in a tertiary hospital. Interventions included group training on pharmacovigilance (PV) and provision of ADR reporting forms amongst others. Assessments were conducted at months 0 and 6 post-interventions using study-specific Likert-type instruments. Mean attitude scores above midpoint of 3.6 on 5-point scale were regarded as positive and below as negative. P<0.05 used to determine statistical significance. Mean age of participants was 36.6 (95%CI, 34.5–38.7) years; 61.1% males; 44.4% doctors, 13.9% pharmacists, 19.4% nurses, 8.3% laboratory scientists, 8.3% record officers and 5.6% welfare officers. None had received training on PV previously. Mean knowledge test score increased from 53.6% (95%CI, 44.6–63.6) at pre-intervention to 77.1% (95%CI, 72.8–81.4) at post-intervention with a mean change of 146.9% (95%CI, 60.5–233.3; p=0.000). Mean rated attitude scores increased from 3.6 (95%CI, 3.4–3.8) at pre-intervention to 4.2 (95%CI, 4.0–4.4) at post-intervention; the difference was statistically significant (p=0.000). 75.8% reported that ADR reporting forms were not readily available at pre-intervention compared to 18.2% at postintervention; 15.2% had reported ADR previously at pre-intervention compared to 69.7% at post-intervention; 12.1% reported providing information regarding ADRs and its management always at pre-intervention compared to 45.5% at post-intervention; these differences were statistically significant (p<0.05). Lack/inadequate knowledge, unavailability of reporting forms and negative attitudes were barriers identified; and addressing them resulted in significant improvement in this setting. Scaling up these interventions to other hospitals can better the situation of under-reporting of ADRs in Nigeria. PMID:24826040

  6. The paradigm of universal access to HIV-treatment and human rights violation: how do we treat HIV-positive people who use drugs?

    PubMed

    Malta, Monica; Ralil da Costa, Michelle; Bastos, Francisco Inácio

    2014-03-01

    HIV-positive people who use drugs (PWUDs) are particularly vulnerable for suboptimal access to highly active antiretroviral therapy (HAART). We conducted a systematic review to identify factors associated with suboptimal HAART access among this population. Studies evaluating HAART access among active PWUDs as a primary outcome, presenting multivariate analysis and conducted after January 1997 were included. Of 122 studies matching the search criteria, only 14 (11.4 %) met the inclusion criteria. All selected studies were prospective cohorts and included young adults, 13 were conducted in North America or western Europe and one in Ukraine. Selected studies measured HAART access using different strategies, however, all identified PWUDs as less likely to receive HAART, when compared to those who never used drugs or former PWUDs. Additional factors associated with suboptimal HAART access include: recent incarceration, lack of health insurance, unstable housing, depression, non-white ethnicity, female PWUDs, and health professionals stigma/prejudice. Factors associated with higher rates of HIV-treatment access included: alcohol and/or drug addiction treatment (especially methadone maintenance therapy), regular source of primary care, treatment and care from the same provider (most of the time) and larger physician experience in HIV-management. PWUDs face a synergy of social and structural factors that influence their suboptimal access to HAART, struggling with poor living conditions, inadequate access to specialized care and stigma/discrimination from health professionals. Renewed strategies and effective interventions should be developed and scaled-up, in order to assure equitable HAART access, decrease morbidity and mortality among PWUDs. PMID:24369409

  7. Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance.

    PubMed

    Valle, Demetrio L; Cabrera, Esperanza C; Puzon, Juliana Janet M; Rivera, Windell L

    2016-01-01

    Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria. PMID:26741962

  8. Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance

    PubMed Central

    Valle, Demetrio L.; Cabrera, Esperanza C.; Puzon, Juliana Janet M.; Rivera, Windell L.

    2016-01-01

    Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria. PMID:26741962

  9. TIRF high-content assay development for the evaluation of drug efficacy of chemotherapeutic agents against EGFR-/HER2-positive breast cancer cell lines.

    PubMed

    Ki, Jieun; Arumugam, Parthasarathy; Song, Joon Myong

    2016-05-01

    Elevated expression of epidermal growth factor receptor (EGFR) is reported to be associated with poor prognosis in breast cancer. EGFR subtype identification plays a crucial role in deciding the drug combination to treat the cancer patients. Conventional application of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) produces more discordance results in EGFR subtype identification of cancer specimens. The present study is designed to develop an analytical method for simultaneous identification of cell surface biomarkers and quantitative estimation of drug efficacy in cancer specimens. For this study, we have utilized a total internal reflection fluorescence microscope (TIRFM), Qdot molecular probes and chemotherapeutic agent camptothecin (CPT)-treated breast cancer cell lines namely MCF-7, SK-BR-3 and JIMT-1. Highly sensitive detection signals with low background noise generated from the evanescent field excitation of TIRFM make it a highly suitable tool to detect the cell surface biomarkers in living cells. Moreover, single wavelength excitation of Qdot probes offers multicolour imaging with strong emission brightness. In the present study, TIRF high-content imaging system simultaneously showed the expression pattern of EGFRs and EC50 value for CPT-induced apoptosis and necrosis in MCF-7, SK-BR-3 and JIMT-1 cancer cell lines. Graphical abstract Schematic illustration of TIRFM high-content assay development for simultaneous identification of EGFR markers and quantitative analysis of drug-induced apoptosis and necrosis in cancer cells. PMID:26886741

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

    PubMed Central

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

    2013-01-01

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

  11. Ado-trastuzumab emtansine (T-DM1): a novel antibody-drug conjugate for the treatment of HER2-positive metastatic breast cancer.

    PubMed

    Baron, Jessica M; Boster, Bonnie L; Barnett, Chad M

    2015-04-01

    Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is an aggressive form of breast cancer associated with poorer prognosis and shortened survival. Primary and acquired resistance to existing HER2-targeted therapies presents a challenge for the management of patients with HER2-positive metastatic breast cancer. Ado-trastuzumab emtansine, a drug-antibody conjugate, has shown promising results for patients failing prior treatment with trastuzumab. Ado-trastuzumab emtansine consists of the monoclonal antibody trastuzumab linked to a potent microtubule inhibitor (emtansine), allowing a targeted delivery of chemotherapy to cells that overexpress HER2. Ado-trastuzumab emtansine has been approved for use in patients with metastatic breast cancer who have failed prior therapy with trastuzumab and a taxane. Although well-tolerated in clinical trials, thrombocytopenia has been reported and platelet values should be monitored closely. Increased liver enzymes and bilirubin, as well as cardiotoxicity, have also been documented, and recommendations for dose reduction or discontinuation due to these toxicities are available. Clinical trials are currently ongoing to further define the role of ado-trastuzumab emtansine in both the metastatic and early breast cancer settings. PMID:24682654

  12. Deep Sequencing of HIV-1 RNA and DNA in Newly Diagnosed Patients with Baseline Drug Resistance Showed No Indications for Hidden Resistance and Is Biased by Strong Interference of Hypermutation.

    PubMed

    Dauwe, Kenny; Staelens, Delfien; Vancoillie, Leen; Mortier, Virginie; Verhofstede, Chris

    2016-06-01

    Deep sequencing of plasma RNA or proviral DNA may be an interesting alternative to population sequencing for the detection of baseline transmitted HIV-1 drug resistance. Using a Roche 454 GS Junior HIV-1 prototype kit, we performed deep sequencing of the HIV-1 protease and reverse transcriptase genes on paired plasma and buffy coat samples from newly diagnosed HIV-1-positive individuals. Selection was based on the outcome of population sequencing and included 12 patients with either a revertant amino acid at codon 215 of the reverse transcriptase or a singleton resistance mutation, 4 patients with multiple resistance mutations, and 4 patients with wild-type virus. Deep sequencing of RNA and DNA detected 6 and 43 mutations, respectively, that were not identified by population sequencing. A subsequently performed hypermutation analysis, however, revealed hypermutation in 61.19% of 3,188 DNA reads with a resistance mutation. The removal of hypermutated reads dropped the number of additional mutations in DNA from 43 to 17. No hypermutation evidence was found in the RNA reads. Five of the 6 additional RNA mutations and all additional DNA mutations, after full exclusion of hypermutation bias, were observed in the 3 individuals with multiple resistance mutations detected by population sequencing. Despite focused selection of patients with T215 revertants or singleton mutations, deep sequencing failed to identify the resistant T215Y/F or M184V or any other resistance mutation, indicating that in most of these cases there is no hidden resistance and that the virus detected at diagnosis by population sequencing is the original infecting variant. PMID:27076656

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

    PubMed Central

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

    2011-01-01

    Pharmacological manipulation of the type 5 metabotropic glutamate (mGlu5) receptor alters various addiction related behaviors such as drug self-administration and the extinction and reinstatement of drug-seeking behavior. However, the effects of pharmacological modulation of mGlu5 receptors on brain reward function have not been widely investigated. We examined the effects of acute administration of positive and negative allosteric modulators (PAMs and NAMs, respectively) on brain reward function by assessing thresholds for intracranial self-stimulation (ICSS). In addition, when acute effects were observed, we examined changes in ICSS thresholds following repeated administration. Male Sprague-Dawley rats were implanted with bipolar electrodes into the medial forebrain bundle and trained to respond for ICSS, followed by assessment of effects of mGlu5 ligands on ICSS thresholds using a discrete trials currentintensity 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

  14. Prevalence of HIV-1 Subtypes and Drug Resistance-Associated Mutations in HIV-1-Positive Treatment-Naive Pregnant Women in Pointe Noire, Republic of the Congo (Kento-Mwana Project).

    PubMed

    Bruzzone, Bianca; Saladini, Francesco; Sticchi, Laura; Mayinda Mboungou, Franc A; Barresi, Renata; Caligiuri, Patrizia; Calzi, Anna; Zazzi, Maurizio; Icardi, Giancarlo; Viscoli, Claudio; Bisio, Francesca

    2015-08-01

    The Kento-Mwana project was carried out in Pointe Noire, Republic of the Congo, to prevent mother-to-child HIV-1 transmission. To determine the prevalence of different subtypes and transmitted drug resistance-associated mutations, 95 plasma samples were collected at baseline from HIV-1-positive naive pregnant women enrolled in the project during the years 2005-2008. Full protease and partial reverse transcriptase sequencing was performed and 68/95 (71.6%) samples were successfully sequenced. Major mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors were detected in 4/68 (5.9%), 3/68 (4.4%), and 2/68 (2.9%) samples, respectively. Phylogenetic analysis of HIV-1 isolates showed a high prevalence of unique recombinant forms (24/68, 35%), followed by CRF45_cpx (7/68, 10.3%) and subsubtype A3 and subtype G (6/68 each, 8.8%). Although the prevalence of transmitted drug resistance mutations appears to be currently limited, baseline HIV-1 genotyping is highly advisable in conjunction with antiretroviral therapy scale-up in resource-limited settings to optimize treatment and prevent perinatal transmission. PMID:25970260

  15. [The characteristics of Gram-positive bacteria isolated from skin lesions observed in ambulatory patients and the assessment of their susceptibility to antimicrobial drugs].

    PubMed

    Sikora, Agnieszka; Kozioł-Montewka, Maria; Bogut, Agnieszka

    2011-01-01

    The bacterial skin and soft-tissue infections occur commonly and are characterized by more or less intensified changes within skin and subcutaneous tissue. The bacterial skin infections give rise to significant therapeutic problems associated with increasing resistance etiological agents of these infections to antibiotics and chemotherapeutics. The aim of this study was to assess the distribution of various Gram-positive microorganisms in skin lesion observed in ambulatory patients in a period from June 2005 to December 2006. There were 116 bacterial strains isolated and identified from clinical samples: Staphylococcus aureus, coagulase - negative staphylococi (S.epidermidis, S. xylosus, S.capitis, S.saccharolyticus), Propionobacterium acnes, Streptococcus spp. (S.agalactiae, S.pyogenes) i Corynebacterium spp. (C. striatum, C. amycolatum, C. aquaticum). In the further part of this study we analyzed a profile of their susceptibility to antibiotics and chemotherapeutics in relation to drugs recommended for the empirical therapy. The resultant resistance patterns among the examined bacterial isolates are indicative of certain divergence between recommended empirical antibiotic therapy and actual antimicrobial susceptibility of many etiologic factors of skin and soft-tissue infections. PMID:21853673

  16. Anti-bacterial performance of azithromycin nanoparticles as colloidal drug delivery system against different gram-negative and gram-positive bacteria

    PubMed Central

    Azhdarzadeh, Morteza; Lotfipour, Farzaneh; Zakeri-Milani, Parvin; Mohammadi, Ghobad; Valizadeh, Hadi

    2012-01-01

    Purpose: Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gram negative bacteria in comparison with Erythromycin. The purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA polymer and to compare the effectiveness of prepared nanoparticles with untreated AZI solution. Methods: AZI NPs were prepared by Modified Quasi-Emulsion Solvent Diffusion method. The antibacterial activities of prepared NPs in comparison with AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC 1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano-formulation were compared to the corresponding untreated AZI. Mean Inhibitory Concentration (MIC) values of AZI were also determined using serial dilution method in nutrient broth medium. Results: Mean IZD of nano-formulations for all indicator bacteria were significantly higher than that of untreated AZI (P<0.01). The enhanced antibacterial efficacy was more dominant in the gram positive species. The MIC values of NPs against the tested bacteria were reduced 8 times in comparison to those of untreated AZI. Conclusion: These results indicated an improved potency of AZI NPs which could be attributed to the modified surface characteristics as well as increased drug adsorption and uptake. PMID:24312766

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

    PubMed Central

    2013-01-01

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

  18. 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

    Durden, David A

    2007-05-01

    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

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

    PubMed Central

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

    2014-01-01

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

  20. Improved sensitivity by use of gas chromatography-positive chemical ionization triple quadrupole mass spectrometry for the analysis of drug related substances.

    PubMed

    Van Gansbeke, Wim; Polet, Michael; Hooghe, Fiona; Devos, Christophe; Van Eenoo, Peter

    2015-09-15

    In 2013, the World Anti-Doping Agency (WADA) drastically lowered the minimum required performance levels (MRPLs) of most doping substances, demanding a substantial increase in sensitivity of the existing methods. For a number of compounds, conventional electron impact ionization gas chromatography tandem mass spectrometry (GC-EI-MS/MS) is often no longer sufficient to reach these MRPLs and new strategies are required. In this study, the capabilities of positive ion chemical ionization (PICI) GC-MS/MS are investigated for a wide range of drug related compounds of various classes by injection of silylated reference standards. Ammonia as PICI reagent gas had superior characteristics for GC-MS/MS purposes than methane. Compared to GC-EI-MS/MS, PICI (with ammonia as reagent gas) provided more selective ion transitions and consequently, increased sensitivity by an average factor of 50. The maximum increase (by factor of 500-1000) was observed in the analysis of stimulants, namely chlorprenaline, furfenorex and phentermine. In total, improved sensitivity was obtained for 113 out of 120 compounds. A new GC-PICI-MS/MS method has been developed and evaluated for the detection of a wide variety of exogenous doping substances and the quantification of endogenous steroids in urine in compliance with the required MRPLs established by WADA in 2013. The method consists of a hydrolysis and extraction step, followed by derivatization and subsequent 1μL pulsed splitless injection on GC-PICI-MS/MS (16min run). The increased sensitivity allows the set up of a balanced screening method that meets the requirements for both quantitative and qualitative compounds: sufficient capacity and resolution in combination with high sensitivity and short analysis time. This resulted in calibration curves with a wide linear range (e.g., 48-9600ng/mL for androsterone and etiochanolone; all r(2)>0.99) without compromising the requirements for the qualitative compounds. PMID:26296082

  1. Hepatitis B Virus Sub-genotype A1 Infection Is Characterized by High Replication Levels and Rapid Emergence of Drug Resistance in HIV-Positive Adults Receiving First-line Antiretroviral Therapy in Malawi

    PubMed Central

    Aoudjane, Samir; Chaponda, Mas; González del Castillo, Antonio Adrián; O'Connor, Jemma; Noguera, Marc; Beloukas, Apostolos; Hopkins, Mark; Khoo, Saye; van Oosterhout, Joep J.; Geretti, Anna Maria

    2014-01-01

    Background. It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing antiretroviral therapy (ART) without tenofovir in Africa. Methods. The virologic expression of HBV sub-genotype A1 coinfection was studied over 12 months in HIV-positive adults starting stavudine/lamivudine/nevirapine in Malawi, using Sanger, deep, clonal, and single full-genome sequencing for the sensitive characterization of HBV resistance-associated mutations (RAMs). Results. Among 1117 subjects, 133 (12%) tested HBsAg-positive. After starting ART, retention rates were 96/133 (72%) at 6 months and 54/133 (41%) at 12 months. Based upon the last available follow-up, 92/96 (96%) subjects achieved HIV-1 RNA <40 copies/mL, 48/96 (50%) showed HBV DNA <14 IU/mL, and 24/96 (25%) acquired HBV RAMs. At 6 months, M204I was detected in 8/46 (17%) and 16/17 (94%) subjects using Sanger and deep sequencing, respectively. At 12 months, all viremic patients had multiple resistance and compensatory mutations coexisting on the same HBV genomes. Comparing HBeA-positive (67/133, 50%) with HBeAg-negative subjects, 64/67 (96%) vs 35/66 (55%) showed baseline HBV DNA >2000 IU/mL (P = .0006), 39/47 (17%) vs 9/49 (82%) had persistent HBV DNA detection during follow-up (P < .0001), and 23/47 (49%) vs 2/49 (4%) acquired HBV RAMs (P < .0001). Baseline HBV DNA levels were median 8.1 vs 5.3 log10 IU/mL in subjects with vs those without treatment-emergent RAMs (P < .0001). Conclusions. HBV sub-genotype A1 infections showed a severe virologic expression in HIV-positive Malawians. The findings strengthen the urgency of interventions to improve ascertainment and management of chronic hepatitis B in the region. PMID:25100867

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

    PubMed Central

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

    2013-01-01

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

  3. Towards Estimation of HIV-1 Date of Infection: A Time-Continuous IgG-Model Shows That Seroconversion Does Not Occur at the Midpoint between Negative and Positive Tests

    PubMed Central

    Skar, Helena; Albert, Jan; Leitner, Thomas

    2013-01-01

    Estimating date of infection for HIV-1-infected patients is vital for disease tracking and informed public health decisions, but is difficult to obtain because most patients have an established infection of unknown duration at diagnosis. Previous studies have used HIV-1-specific immunoglobulin G (IgG) levels as measured by the IgG capture BED enzyme immunoassay (BED assay) to indicate if a patient was infected recently, but a time-continuous model has not been available. Therefore, we developed a logistic model of IgG production over time. We used previously published metadata from 792 patients for whom the HIV-1-specific IgG levels had been longitudinally measured using the BED assay. To account for patient variability, we used mixed effects modeling to estimate general population parameters. The typical patient IgG production rate was estimated at r = 6.72[approximate 95% CI 6.17,7.33]×10−3 OD-n units day−1, and the carrying capacity at K = 1.84[1.75,1.95] OD-n units, predicting how recently patients seroconverted in the interval ∧t = (31,711) days. Final model selection and validation was performed on new BED data from a population of 819 Swedish HIV-1 patients diagnosed in 2002–2010. On an appropriate subset of 350 patients, the best model parameterization had an accuracy of 94% finding a realistic seroconversion date. We found that seroconversion on average is at the midpoint between last negative and first positive HIV-1 test for patients diagnosed in prospective/cohort studies such as those included in the training dataset. In contrast, seroconversion is strongly skewed towards the first positive sample for patients identified by regular public health diagnostic testing as illustrated in the validation dataset. Our model opens the door to more accurate estimates of date of infection for HIV-1 patients, which may facilitate a better understanding of HIV-1 epidemiology on a population level and individualized prevention, such as guidance during contact tracing. PMID:23613753

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

    PubMed Central

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Silva, Roberta K.

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

  6. Use of Compassionate Supply of Antiretroviral Drugs to Avoid Treatment Interruptions or Delayed Treatment Initiation among HIV-Positive Patients Living in Ontario: A Retrospective Review

    PubMed Central

    Naccarato, Mark; Gough, Kevin; Lewis, Jordan; Bayoumi, Ahmed M.

    2015-01-01

    Background: Without a national pharmacare plan in Canada, HIV-infected patients across the nation differ in their ability to obtain essential HIV therapy. Despite the fact there are public insurance programs in Ontario, patients are unable to access medication. The authors described how frequently patients in their urban clinic could not access medications and why they required a compassionate supply of HIV drugs, with the goals of minimizing treatment delays and avoiding interruptions. Methods: The authors conducted a retrospective review and collected information about demographic characteristics, current drug insurance and the challenges encountered. Results: Over one year, the authors provided 2,886 days of free HIV drugs to 42 patients who were predominantly citizens or permanent residents of Canada (88%). The most common obstacles were associated with the Trillium Drug Program and the total value of all drugs supplied was $134,860. Interpretation: This study suggests that Ontario's catastrophic drug insurance plan leaves some patients with significant gaps in drug coverage. PMID:25947034

  7. Drug Addiction

    PubMed Central

    Justinova, Zuzana; Panlilio, Leigh V.; Goldberg, Steven R.

    2011-01-01

    Many drugs of abuse, including cannabinoids, opioids, alcohol and nicotine, can alter the levels of endocannabinoids in the brain. Recent studies show that release of endocannabinoids in the ventral tegmental area can modulate the reward-related effects of dopamine and might therefore be an important neurobiological mechanism underlying drug addiction. There is strong evidence that the endocannabinoid system is involved in drug-seeking behavior (especially behavior that is reinforced by drug-related cues), as well as in the mechanisms that underlie relapse to drug use. The cannabinoid CB1 antagonist/inverse agonist rimonabant has been shown to reduce the behavioral effects of stimuli associated with drugs of abuse, including nicotine, alcohol, cocaine, and marijuana. Thus, the endocannabinoid system represents a promising target for development of new treatments for drug addiction. PMID:21104390

  8. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  9. [THE EFFECTIVENESS OF A 10-DAY DRUG THERAPY IN CHILDREN WITH CHRONIC GASTRODUODENAL PATHOLOGY ASSOCIATED WITH CAGA-POSITIVE STRAINS OF HELICOBACTER PYLORI].

    PubMed

    Dudnyk, V M; Rudenko, G M

    2015-01-01

    The results of triple Helicobacter-therapy (omeprazole, amoxicillin, nifuratel) in the treatment of chronic gastroduodenal pathology in children depending on the duration of it's use. The effectiveness of drug therapy was evaluated in terms of eradication of Helicobacter pylori and dynamics of pain, dyspeptic syndrome and astenovegetative syndrome. PMID:26118054

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

    PubMed

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

    2014-11-01

    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

  11. Drugged Driving

    MedlinePlus

    ... Data from a 2011 survey of middle and high school students showed that in the 2 weeks before ... Driving after drug or alcohol use by US high school seniors, 2001-2011. Am J Public Health . 2013; ...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

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

  15. Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.

    PubMed

    Yin, Lei; Wang, Tingting; Shi, Meiyun; Zhang, Ying; Zhao, Xiaojun; Yang, Yan; Gu, Jingkai

    2016-03-01

    A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. PMID:26711223

  16. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

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

  17. Obesity in show cats.

    PubMed

    Corbee, R J

    2014-12-01

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

  18. Show What You Know

    ERIC Educational Resources Information Center

    Eccleston, Jeff

    2007-01-01

    Big things come in small packages. This saying came to the mind of the author after he created a simple math review activity for his fourth grade students. Though simple, it has proven to be extremely advantageous in reinforcing math concepts. He uses this activity, which he calls "Show What You Know," often. This activity provides the perfect…

  19. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

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

  20. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

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

  1. Assemblage of drug release modules: effect of module shape and position in the assembled systems on floating behavior and release rate.

    PubMed

    Hascicek, C; Rossi, A; Colombo, P; Massimo, G; Strusi, O L; Colombo, G

    2011-01-01

    The aim of this work was to study the clindamycin release kinetics from floating delivery systems consisting of two modules assembled in void configuration, according to the modified release technology platform known as Dome Matrix. Two modules differently shaped, i.e., female and male, formulated as swellable matrices and containing clindamycin, were assembled by friction interlocking. Then, by stacking additional female modules without drug on the assembled two-module floating system, modulation of clindamycin release rate and kinetics was attained. The additional modules stacked on the assembled system acted as a transient barrier to clindamycin release from the void configuration. Inertness, dissolution/erosion or swelling behavior characterized their performance as matrices in simulated gastric fluid. In particular, we found that stacking additional barrier modules on the bases of void configuration, the drug release rate and kinetics of the assembled system were modified in dependence on the composition of module added. In particular, the quickly soluble module exerted an influence on the release rate in the late time of delivery. The swellable module produced a significant reduction in release rate of void assembly, but the release mechanism remained the same. Finally, the inert module led to a substantial linearization of the release profile with a minimal reduction in release rate. PMID:21087663

  2. 21 CFR 1314.150 - Order To show cause.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Order To show cause. 1314.150 Section 1314.150 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RETAIL SALE OF SCHEDULED LISTED CHEMICAL PRODUCTS Order to Show Cause § 1314.150 Order To show cause. (a) If, upon information gathered...

  3. P1 and P1' para-fluoro phenyl groups show enhanced binding and favorable predicted pharmacological properties: structure-based virtual screening of extended lopinavir analogs against multi-drug resistant HIV-1 protease

    PubMed Central

    Yedidi, Ravikiran S.; Liu, Zhigang; Kovari, Iulia A.; Woster, Patrick M.; Kovari, Ladislau C.

    2013-01-01

    Crystal structure of multidrug-resistant (MDR) clinical isolate 769, human immunodeficiency virus type-1 (HIV-1) protease in complex with lopinavir (LPV) (PDB ID: 1RV7) showed altered binding orientation of LPV in the expanded active site cavity, causing loss of contacts and decrease in potency. In the current study, with a goal to restore the lost contacts, three libraries of LPV analogs containing extended P1 and/or P1' phenyl groups were designed and docked into the expanded active site cavity of the MDR769 HIV-1 protease. The compounds were then ranked based on three criteria: binding affinity, overall binding profile and predicted pharmacological properties. Among the twelve proposed extensions in different combinations, compound 14 (consists of para-fluoro phenyl group as both P1 and P1' moieties) was identified as a lead with improved binding profile, binding affinity against the MDR protease and favorable predicted pharmacological properties comparable to those of LPV. The binding affinity of 14 against wild type (NL4-3) HIV-1 protease was comparable to that of LPV and was better than LPV against an ensemble of MDR HIV-1 protease variants. Thus, 14 shows enhanced binding affinity by restoring lost contacts in the expanded active site cavity of MDR769 HIV-1 protease variants suggesting that it may have higher potency compared to that of LPV and hence should be further synthesized and evaluated against NL4-3 as well as MDR variants of HIV-1. PMID:24291501

  4. Obesity in show dogs.

    PubMed

    Corbee, R J

    2012-08-11

    Obesity is an important disease with a growing incidence. Because obesity is related to several other diseases, and decreases life span, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain breeds is often suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, we investigated 1379 dogs of 128 different breeds by determining their body condition score (BCS). Overall, 18.6% of the show dogs had a BCS >5, and 1.1% of the show dogs had a BCS>7. There were significant differences between breeds, which could be correlated to the breed standards. It warrants firm discussions with breeders and judges in order to come to different interpretations of the standards to prevent overweight conditions from being the standard of beauty. PMID:22882163

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

    PubMed

    Dohle, Simone; Siegrist, Michael

    2014-10-01

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

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

    PubMed

    Davis, Gregory G

    2014-03-01

    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

  7. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show. PMID:23631336

  8. [Identification, during development, of a methodology targeted at determining the positioning of new drugs for therapeutic strategies: examples of rheumatoid arthritis and cardiac insufficiency].

    PubMed

    Le Jeunne, C; Plétan, Y; Boissel, J P

    2002-01-01

    The Marketing Authorization (MA) granted to a new molecular entity does not allow for proper anticipation of its future positioning within the therapeutic strategy. A specific methodology should be devised as early as during the pre-MA development phase that could result in an initial positioning that should be subjected to further reappraisal with regard to scientific advances, the arrival of new treatments and further developments with this molecule. A methodology is thus proposed, based on early optimisation of the development plan, the granting of subsequent MAs, and reappraisal of the positioning within the strategy, based on analysis of all available data. It should be possible to take into account the economic context, within an agreed system with pre-defined medico-economic criteria. This may in turn raise the issue of the role of the various parties involved in this assessment, as well as how to understand the respective opinions of stakeholders: authorities, sponsors, prescribers and patients, each of whom has a specific view of the definition of the strategic objective that should apply to the disease concerned. PMID:12422553

  9. 5-(Bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA): showing a strategy of designing drug to block lung metastasis of tumors

    PubMed Central

    Gan, Taiping; Wang, Yuji; Zhao, Ming; Wu, Jianhui; Yang, Jian; Peng, Shiqi

    2016-01-01

    Early metastasis is still the most recalcitrant factor in the treatment of lung cancer patients. By analyzing the structures and comparing the docking scores of the known pharmacophores, the authors of this paper designed 5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA) as a promising lead compound to develop metastasis inhibitors. In vitro 5, 10, and 20 µM of BHIMHA concentration dependently inhibited the migration and invasion of A549 cells. In vivo 0.4, 2.0, and 8.9 µmol/kg of BHIMHA dose dependently inhibited the metastasis of LLC (Lewis Lung Carcinoma) toward lung. In vivo, 2 µmol/kg of BHIMHA showed additional actions of slowing the growth of the primary tumor of C57BL/6 mice and S180 mice as well as inhibiting xylene-induced ear edema of the mice. Therefore, BHIMHA simultaneously blocked tumor metastasis toward lung, slowed the primary tumor growth, and limited the inflammation. These pharmacological actions were correlated with the inhibition of PKCα and NF-κB expression. PMID:26937173

  10. 5-(Bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA): showing a strategy of designing drug to block lung metastasis of tumors.

    PubMed

    Gan, Taiping; Wang, Yuji; Zhao, Ming; Wu, Jianhui; Yang, Jian; Peng, Shiqi

    2016-01-01

    Early metastasis is still the most recalcitrant factor in the treatment of lung cancer patients. By analyzing the structures and comparing the docking scores of the known pharmacophores, the authors of this paper designed 5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA) as a promising lead compound to develop metastasis inhibitors. In vitro 5, 10, and 20 µM of BHIMHA concentration dependently inhibited the migration and invasion of A549 cells. In vivo 0.4, 2.0, and 8.9 µmol/kg of BHIMHA dose dependently inhibited the metastasis of LLC (Lewis Lung Carcinoma) toward lung. In vivo, 2 µmol/kg of BHIMHA showed additional actions of slowing the growth of the primary tumor of C57BL/6 mice and S180 mice as well as inhibiting xylene-induced ear edema of the mice. Therefore, BHIMHA simultaneously blocked tumor metastasis toward lung, slowed the primary tumor growth, and limited the inflammation. These pharmacological actions were correlated with the inhibition of PKCα and NF-κB expression. PMID:26937173

  11. The Power of Positive Emotions

    MedlinePlus

    ... Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I Help a Friend Who Cuts? The Power of Positive Emotions KidsHealth > For Teens > The Power of Positive Emotions ...

  12. [Comparison of four drug interaction screening programs].

    PubMed

    Ing Lorenzini, K; Reutemann, B; Samer, C F; Guignard, B; Bonnabry, P; Dayer, P; Perrier, A; Desmeules, J

    2012-10-17

    Adverse drug events (ADE) are a major public health issue, with drug-drug interactions (DDI) being one of well-recognized causes of ADE that could be preventable by the use of DDI screening software. We compared the ability of four programs to detect clinically important DDI. We tested 62 drug pairs with and 12 drug pairs without clinically important DDI. Lexi-Interact and Epocrates were the most sensitive (95%) compared to the Compendium and Theriaque (80 and 73%, respectively). The Compendium and Theriaque also showed the lowest negative predictive value. All programs showed high specificity and positive predictive value. The qualitative assessment showed the best performances for Compendium and Lexi-Interact. The last one seems to be the best screening program, but the Compendium is in French and is freely available. PMID:23198652

  13. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

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

  14. "Show me" bioethics and politics.

    PubMed

    Christopher, Myra J

    2007-10-01

    Missouri, the "Show Me State," has become the epicenter of several important national public policy debates, including abortion rights, the right to choose and refuse medical treatment, and, most recently, early stem cell research. In this environment, the Center for Practical Bioethics (formerly, Midwest Bioethics Center) emerged and grew. The Center's role in these "cultural wars" is not to advocate for a particular position but to provide well researched and objective information, perspective, and advocacy for the ethical justification of policy positions; and to serve as a neutral convener and provider of a public forum for discussion. In this article, the Center's work on early stem cell research is a case study through which to argue that not only the Center, but also the field of bioethics has a critical role in the politics of public health policy. PMID:17926217

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

    PubMed Central

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

    2015-01-01

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

  16. Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya

    PubMed Central

    Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

    2016-01-01

    Introduction Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. Methods We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients’ characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Results Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. Conclusions In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized resistance testing to design effective subsequent regimens. PMID:27231099

  17. How We Can Make a Difference: About Drug Abuse and Young People.

    ERIC Educational Resources Information Center

    Reagan, Nancy

    1986-01-01

    Nancy Reagan discusses the problems of drug abuse by youth. The 1985 findings of the National Institute on Drug Abuse show a decline in marijuana and alcohol use by high school seniors. Mrs. Reagan emphasizes the importance of family support and the parent group movement as well as positive peer group support in the fight against youth drug abuse.…

  18. Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.

    PubMed

    Shah, Manisha H; Lorigan, Paul; O'Brien, Mary E R; Fossella, Frank V; Moore, Kathleen N; Bhatia, Shailender; Kirby, Maurice; Woll, Penella J

    2016-06-01

    Background IMGN901 is a CD56-targeting antibody-drug conjugate designed for tumor-selective delivery of the cytotoxic maytansinoid DM1. This phase 1 study investigated the safety, tolerability, pharmacokinetics, and preliminary activity of IMGN901 in patients with CD56-expressing solid tumors. Methods Patients were enrolled in cohorts of escalating IMGN901 doses, administered intravenously, on 3 consecutive days every 21 days. A dose-expansion phase accrued patients with small cell lung cancer (SCLC), Merkel cell carcinoma (MCC), or ovarian cancer. Results Fifty-two patients were treated at doses escalating from 4 to 94 mg/m(2)/day. The maximum tolerated dose (MTD) was determined to be 75 mg/m(2). Dose-limiting toxicities included fatigue, neuropathy, headache or meningitis-like symptoms, chest pain, dyspnea, and myalgias. In the dose-expansion phase (n = 45), seven patients received 75 mg/m(2) and 38 received 60 mg/m(2) for up to 21 cycles. The recommended phase 2 dose (RP2D) was established at 60 mg/m(2) during dose expansion. Overall, treatment-emergent adverse events (TEAEs) were experienced by 96.9 % of all patients, the majority of which were Grade 1 or 2. The most commonly reported Grade 3 or 4 TEAEs were hyponatremia and dyspnea (each 8.2 %). Responses included 1 complete response (CR), 1 clinical CR, and 1 unconfirmed partial response (PR) in MCC; and 1 unconfirmed PR in SCLC. Stable disease was seen for 25 % of all evaluable patients who received doses ≥60 mg/m(2). Conclusions The RP2D for IMGN901 of 60 mg/m(2) administered for 3 consecutive days every 3 weeks was associated with an acceptable tolerability profile. Objective responses were observed in patients with advanced CD56+ cancers. PMID:26961907

  19. Drug-induced reduction in estimated glomerular filtration rate in patients with ALK-positive non-small cell lung cancer treated with the ALK-inhibitor crizotinib

    PubMed Central

    Brosnan, Evelyn M.; Weickhardt, Andrew J.; Lu, Xian; Maxon, Delee A; Barón, Anna E.; Chonchol, Michel; Camidge, D. Ross

    2014-01-01

    Background Renal side effects of crizotinib have not been investigated previously. Methods Estimated Glomerular Filtration Rate (eGFR) was calculated using the CKD-EPI creatinine-based prediction equation during the first 12 weeks of crizotinib and post-crizotinib prior to the introduction of any further systemic therapy. Results 38 stage IV ALK+ NSCLC patients treated with crizotinib were identified. Mean eGFR fell 23.9% compared to baseline (p<0.0001, 95%CI: 21.3% - 26.6%), with most of the fall occurring within the first 2 weeks of therapy. Clinical history and BUN/creatinine ratios did not suggest prerenal causes. The objective response rate among evaluable patients (n=27) was 41%. Tumor shrinkage was not correlated with changes in eGFR (r = -0.052 (p=0.798)). Among 16 patients with post-crizotinib data, recovery to within 84% of baseline eGFR occurred in all patients. After adjusting for the number of scans with IV contrast and use of known nephrotoxic drugs, whether a patient was on or off crizotinib was significantly associated with changes in eGFR (p<0.0001). Conclusions Assessed by the CKI-EPI prediction equation, eGFR is reduced by crizotinib but most patients will recover their eGFR after cessation of therapy. The early onset, size of change, minimal cumulative effect and rapid reversibility raise the possibility that this may be a pharmacological and/or tubular creatinine secretion effect rather than a direct nephrotoxic effect. Increased vigilance with regard to the concomitant use of renally cleared medications or nephrotoxic agents should be considered for patients receiving crizotinib and, when eGFR is reduced, additional renal investigations undertaken. PMID:24258622

  20. Melanoma Drug Boosting Survival for Many, Study Shows

    MedlinePlus

    ... how to fight and control melanoma," said Dr. Michael Postow, an oncologist specializing in immunotherapy with Memorial ... co-director, gynecologic oncology, Massachusetts General Hospital, Boston; Michael Postow, M.D., oncologist, Memorial Sloan Kettering Cancer ...

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

    MedlinePlus

    ... Care Obesity at Midlife May Speed Alzheimer’s Onset Hello from my mom Easing the Behavior Problems of ... Managers Continuing Care FOR MORE ARTICLES CLICK HERE Hello from my mom Common Estate Planning Errors Alzheimer’s ...

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Effects of PEMF on a murine osteosarcoma cell line: drug-resistant (P-glycoprotein-positive) and non-resistant cells.

    PubMed

    Miyagi, N; Sato, K; Rong, Y; Yamamura, S; Katagiri, H; Kobayashi, K; Iwata, H

    2000-02-01

    After pulsed exposure of Dunn osteosarcoma cells (nonresistant cells) to Adriamycin (ADR) at increasing concentrations and single-cell cloning of surviving cells, ADR-resistant cells were obtained. These resistant cells expressed P-glycoprotein and had resistance more than 10 times that of their nonresistant parent cells. Compared to the nonresistant cells not exposed to pulsing electromagnetic fields (PEMF) in ADR-free medium, their growth rates at ADR concentrations of 0.01 and 0.02 micrograms/ml, which were below IC50, were 83.0% and 61.8%, respectively. On the other hand, in the nonresistant cells exposed to PEMF (repetition frequency, 10 Hz; rise time, 25 microsec, peak magnetic field intensity, 0.4-0.8 mT), the growth rate was 111.9% in ADR-free medium, 95.5% at an ADR concentration of 0.01 micrograms/ml, and 92.2% at an ADR concentration of 0.02 micrograms/ml. This promotion of growth by PEMF is considered to be a result of mobilization of cells in the non-proliferative period of the cell cycle due to exposure to PEMF. However, at ADR concentrations above the IC50, the growth rate tended to decrease in the cells not exposed to PEMF. This may be caused by an increase in cells sensitive to ADR resulting from mobilization of cells in the non-proliferative period to the cell cycle. The growth rate in the resistant cells exposed to PEMF was significantly lower than that in the non-exposed resistant cells at all ADR concentrations, including ADR-free culture (Pshows the potentiality of PEMF as an adjunctive treatment method for malignant tumors. PMID:10653622

  5. Drug Usage and Attitude Toward Drugs Among College Students

    ERIC Educational Resources Information Center

    Cross, Herbert J.; Keir, Richard G.

    1971-01-01

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

  6. Evaluation of the NexScreen and DrugCheck Waive RT urine drug detection cups.

    PubMed

    Lin, Chia-Ni; Nelson, Gordon J; McMillin, Gwendolyn A

    2013-01-01

    Urine drug testing is an important tool that is commonly used to assess patient compliance with prescription regimens. Point-of-collection immunoassay devices allow for timely availability of laboratory test results to guide therapy during the same office visit. Two waived immunoassay-based urine drug screen cups were evaluated in this study. The NexScreen cup and the DrugCheck Waive RT cup claim to detect 10-12 drug classes of commonly used and/or abused drugs. This study included a sensitivity and precision challenge with 4-6 replicates at concentrations 0-150% of the manufacture's claimed cutoff, using drug-free urine spiked with purified reference standards. The stability of test results was evaluated by reading the results at intervals between five and 1,440 min. Specificity was evaluated by parallel comparison of pooled patients' specimens, representing 56 patients and 41 known drug compounds. When comparing results to validated liquid chromatography-mass spectrometry results, false positives were observed in the NexScreen cups for benzodiazepine, methamphetamine, methadone, opiates and tricyclic antidepressant tests, but there were no false negatives. The DrugCheck Waive RT cups showed false negative results for barbiturates and opiates, but no false positives. Overall, the NexScreen cup demonstrated better sensitivity than claimed, whereas the sensitivity of the DrugCheck Waive RT cup did not meet claims. PMID:23144203

  7. Positive Psychology

    ERIC Educational Resources Information Center

    Peterson, Christopher

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  9. Club Drugs

    MedlinePlus

    ... and basic facts about different drugs within this classification of drugs. En Español Methamphetamine (Research Reports) Published ... and basic facts about different drugs within this classification of drugs. Read more NIDA's Publication Series Brain ...

  10. Drug allergies

    MedlinePlus

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

  11. Drug Safety

    MedlinePlus

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

  12. Nursing Positions

    MedlinePlus

    ... breast with your other hand. The Clutch or Football Hold This is also a good position for ... same time may also choose this position. The football hold allows babies to take milk more easily — ...

  13. Primary drug resistance to anti-tuberculosis drugs in major towns of Amhara region, Ethiopia.

    PubMed

    Yimer, Solomon Abebe; Agonafir, Mulualem; Derese, Yohannes; Sani, Yusuf; Bjune, Gunnar A; Holm-Hansen, Carol

    2012-06-01

    Drug resistance is a major obstacle to effective TB control program performance. In this study, we assessed the prevalence of primary drug resistance in Mycobacterium tuberculosis (Mtb) isolates in Amhara Region, Ethiopia. A total of 112 Mtb isolates from cases with newly diagnosed pulmonary TB were subjected to drug susceptibility testing (DST) in a cross-sectional study. Isolates were tested for sensitivity to isoniazid, rifampicin, ethambutol, and streptomycin using the MGIT 960 protocol. A total of 93 Mtb isolates yielded valid DST results and 28 (30.1%) were resistant to one or more of first line anti-TB drugs. One isolate (1.0%) was multi-drug resistant (MDR), five (5.4%) were classified as poly-resistant and 22 showed single drug resistance to either streptomycin (n = 19) or isoniazid (n = 3). Isolates from HIV-positive patients were more likely to be resistant to at least one of the four anti-TB drugs compared with HIV-negative individuals (odds ratio 2.76, 95% confidence interval 1.06-7.22; p = 0.03). The study showed a high prevalence of primary drug resistance. Even though the prevalence of MDR was low, conditions that can contribute to the development of MDR are increasing. Therefore, regular monitoring of drug resistance and enhanced implementation of TB/HIV collaborative activities in the study region are imperative. PMID:22583363

  14. Positive Psychology

    ERIC Educational Resources Information Center

    Peterson, Christopher

    2009-01-01

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

  15. Drug therapy smartens up

    NASA Astrophysics Data System (ADS)

    Martin, Christian

    2015-11-01

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

  16. The Drug War.

    ERIC Educational Resources Information Center

    DeCrosta, Anthony

    1989-01-01

    The role of teachers in helping fight against drug abuse is discussed stressing the teacher's ability to see changes in the students and the potential for positive influence. A vital school role involves teaching life skills and wellness principles. Information on commonly abused drugs and their effects is presented. (SM)

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

    PubMed Central

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

    2012-01-01

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

  18. Thermotropic liquid crystalline drugs.

    PubMed

    Bunjes, Heike; Rades, Thomas

    2005-07-01

    Crystalline solids are characterized by long-range positional and orientational order in three dimensions, whereas amorphous liquids lack long-range order in any dimension. Liquid crystals (mesophases) show structural, mechanical and optical properties intermediate to those of crystalline solids and the amorphous, liquid state of matter. There are two principle types of liquid crystals: thermotropic liquid crystals (TLCs) and lyotropic liquid crystals (LLCs). TLCs can be formed by heating a crystalline solid or by cooling an isotropic melt of a TLC-forming molecule (mesogen). In the first part of this review the types of liquid crystals are defined and classified and the structural properties of mesogens are explained. In the second part, ten case studies of thermotropic mesomorphous drugs and pharmaceutically relevant molecules (arsphenamine, nafoxidine hydrochloride, L-660711, palmitoyl propranolol hydrochloride, penbutolol sulfate, itraconazole hydrochloride, fenoprofen sodium, fenoprofen calcium, ciclosporin and cholesteryl esters) are presented and their thermotropic mesomorphism is described. The review closes with a brief discussion of the unusual properties of drug mesophases and a potential use of drugs and excipients in this fourth state of matter. PMID:15969938

  19. Scaring Kids' Shows Off TV.

    ERIC Educational Resources Information Center

    Raspberry, William

    1980-01-01

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

  20. Gender differences in psychopathy links to drug use.

    PubMed

    Schulz, Nicole; Murphy, Brett; Verona, Edelyn

    2016-04-01

    Although the relationship between psychopathic personality traits and substance use has received some attention (Hart & Hare, 1989; Smith & Newman, 1990), gender differences have not been thoroughly assessed. The current study examined whether gender modified the relationship between 2 criminally relevant constructs, (a) psychopathy and its factors and (b) drug use. A sample of 318 participants with criminal histories and recent substance use was assessed for psychopathy using the Psychopathy Checklist: Screening Version and for illicit drug use using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. As expected, the impulsive-antisocial traits (Factor 2) of psychopathy were positively related to a number of drug use characteristics (symptoms, age of drug initiation, extent of drug experimentation), whereas the interpersonal-affective traits (Factor 1) showed a negative relationship with drug abuse symptoms and a positive relationship with age of first use. In terms of gender differences, analyses revealed that women showed a stronger association between Factor 1 traits and later age of initiation compared to men, and that Factor 2, and the antisocial facet in particular, were more strongly related to drug abuse in women than men. These findings suggest that psychopathic traits serve as both protective (Factor 1) and risk (Factor 2) correlates of illicit drug use, and Factor 1 may be especially protective in terms of initiation of drug use among women. These conclusions add to the growing literature on potential routes to substance use and incarceration in women. (PsycINFO Database Record PMID:26571339

  1. Photon beam position monitor

    SciTech Connect

    Izumi, T.; Nakajima, T.; Kurihama, T.

    1989-07-01

    A highly sensitive beam position monitor has been designed for use with synchrotron radiation sources. This beam position monitor consists of two gas-flow ionization chambers having three parallel plate conductors. The incident beam is divided by a central plate. Therefore, a displacement of the beam position is detected with the two outside ionization chambers. The position monitor was tested at the BL6Cl beamline of the Photon Factory (PF). The results show a good performance.

  2. Positive Psychotherapy

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  3. Positive Psychotherapy

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  4. Positioning Agility

    NASA Astrophysics Data System (ADS)

    Oza, Nilay; Abrahamsson, Pekka; Conboy, Kieran

    Agile methods are increasingly adopted by European companies. Academics too are conducting numerous studies on different tenets of agile methods. Companies often feel proud in marketing themselves as ‘agile’. However, the true notion of ‘being agile’ seems to have been overlooked due to lack of positioning of oneself for agility. This raises a call for more research and interactions between academia and the industry. The proposed workshop refers to this call. It will be highly relevant to participants, interested in positioning their company’s agility from organizational, group or project perspectives. The positioning of agility will help companies to better align their agile practices with stakeholder values. Results of the workshop will be shared across participants and they will also have opportunity to continue their work on agile positioning in their companies. At broader level, the work done in this workshop will contribute towards developing Agile Positioning System.

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

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

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

  6. 1. Contextual view of cottage, showing front east elevation, showing ...

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

    1. Contextual view of cottage, showing front east elevation, showing in distance blacksmith shop (left) and summer kitchen (right); camera facing southwest. - Lemmon-Anderson-Hixson Ranch, Cottage, 11220 North Virginia Street, Reno, Washoe County, NV

  7. 4. View of west elevation, showing stone structure, showing a ...

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

    4. View of west elevation, showing stone structure, showing a portion of north elevation; camera facing southeast. - Lemmon-Anderson-Hixson Ranch, Cottage, 11220 North Virginia Street, Reno, Washoe County, NV

  8. Drugs in oral fluid in randomly selected drivers.

    PubMed

    Drummer, Olaf H; Gerostamoulos, Dimitri; Chu, Mark; Swann, Philip; Boorman, Martin; Cairns, Ian

    2007-08-01

    There were 13,176 roadside drug tests performed in the first year of the random drug-testing program conducted in the state of Victoria. Drugs targeted in the testing were methamphetamines and Delta(9)-tetrahydrocannabinol (THC). On-site screening was conducted by the police using DrugWipe, while the driver was still in the vehicle and if positive, a second test on collected oral fluid, using the Rapiscan, was performed in a specially outfitted "drug bus" located adjacent to the testing area. Oral fluid on presumptive positive cases was sent to the laboratory for confirmation with limits of quantification of 5, 5, and 2 ng/mL for methamphetamine (MA), methylenedioxy-methamphetamine (MDMA), and THC, respectively. Recovery experiments conducted in the laboratory showed quantitative recovery of analytes from the collector. When oral fluid could not be collected, blood was taken from the driver and sent to the laboratory for confirmation. These roadside tests gave 313 positive cases following GC-MS confirmation. These comprised 269, 118, and 87 cases positive to MA, MDMA, and THC, respectively. The median oral concentrations (undiluted) of MA, MDMA, and THC was 1136, 2724, and 81 ng/mL. The overall drug positive rate was 2.4% of the screened population. This rate was highest in drivers of cars (2.8%). The average age of drivers detected with a positive drug reading was 28 years. Large vehicle (trucks over 4.5 t) drivers were older; on average at 38 years. Females accounted for 19% of all positives, although none of the positive truck drivers were female. There was one false positive to cannabis when the results of both on-site devices were considered and four to methamphetamines. PMID:17658711

  9. Antitumor drugs as photochemotherapeutic agents

    NASA Astrophysics Data System (ADS)

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

    1991-11-01

    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.

  10. 15. Detail showing lower chord pinconnected to vertical member, showing ...

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

    15. Detail showing lower chord pin-connected to vertical member, showing floor beam riveted to extension of vertical member below pin-connection, and showing brackets supporting cantilevered sidewalk. View to southwest. - Selby Avenue Bridge, Spanning Short Line Railways track at Selby Avenue between Hamline & Snelling Avenues, Saint Paul, Ramsey County, MN

  11. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  12. Drug Abuse

    MedlinePlus

    ... a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug abuse in the first place. NIH: National Institute on Drug Abuse

  13. Microfluidic device for drug delivery

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  14. Relationships Between Illicit Drug Use and Body Mass Index Among Adolescents.

    PubMed

    Blackstone, Sarah R; Herrmann, Lynn K

    2016-02-01

    Prior research has established associations between body mass index (BMI) and use of alcohol, tobacco, and marijuana. However, little research has been done investigating the relationship between other common illicit drugs and BMI trends. The present study investigated whether adolescents who reported using illicit drugs showed differences in BMI compared to peers who reported no drug use. There was a positive relationship between drug use and BMI as well as the number of drugs used and BMI. The results suggested that the positive relationship between the use of illicit drugs and BMI is largely due to smoking. Further research needs to ascertain whether smoking, illicit drug use, or both are among the first of many unhealthy behaviors that can subsequently lead to greater gains in BMI. Implications for health educators are discussed. PMID:25842387

  15. 3 Ways to Increase Positive Emotions

    MedlinePlus

    ... Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I Help a Friend Who Cuts? 3 Ways to Increase Positive Emotions KidsHealth > For Teens > 3 Ways to Increase Positive ...

  16. Evaluation of a lymph node proliferation assay for its ability to detect pharmaceuticals with potential to cause immune-mediated drug reactions.

    PubMed

    Weaver, James L; Chapdelaine, Joan M; Descotes, Jacques; Germolec, Dori; Holsapple, Mike; House, Robert; Lebrec, Herve; Meade, Jean; Pieters, Raymond; Hastings, Kenneth L; Dean, Jack H

    2005-01-01

    Hypersensitivity reactions to systemically administered drugs cannot be predicted using available preclinical models. This research is a collaborative project to evaluate the ability of the Lymph Node Proliferation Assay (LNPA) to predict systemic hypersensitivity caused by pharmaceuticals. The assay design is a modification of the Local Lymph Node Assay with the major modification being injection of the test substance subcutaneously to achieve a known systemic exposure to the drug. Fourteen compounds were evaluated in the LNPA. These were two clinically negative drugs (Metformin, phenobarbital), an assay positive control (streptozotocin), eight human hypersensitivity positive drugs (sulfamethoxazole, procainamide, clonidine, ofloxacin, nevirapine, abacavir, lamotrigine, zomepirac), and 3 investigational drugs (CM40874, CM40954 and CM40420), one of which caused hypersensitivity in primates. Hypersensitivity-positive drugs were classified as such based on at least two of three independent data sources: U.S. FDA postmarketing database, drug labeling information, and clinical trial data. All drugs were tested in multiple laboratories for a total of 2-12 evaluations per compound. The pure drug substance was used for testing if it could be obtained commercially, otherwise the marketed drug formulation was used. Neither of the negative control drugs showed a positive reaction in the test system. Four of the eight hypersensitivity positive drugs showed a mixed or positive reaction. Two of the three investigational compounds gave a positive response. A smaller number of LNPAs were run concurrently using footpad injection and evaluation of the popliteal lymph node and gave generally comparable results. Additional development may increase the reproducibility of the assay and facilitate detection of drugs that require metabolic activation to become allergenic, or drugs for which there is dose-limiting toxicity. The data suggest that this method might be useful as a first-line screen to identify candidate drugs that are more likely to cause a high prevalence of human drug hypersensitivity. PMID:18958655

  17. Overview of Selected Drug Trends.

    ERIC Educational Resources Information Center

    Adams, Edgar H.; And Others

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

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

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

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

  19. Show Them You Really Want the Job

    ERIC Educational Resources Information Center

    Perlmutter, David D.

    2012-01-01

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

  20. Show Them You Really Want the Job

    ERIC Educational Resources Information Center

    Perlmutter, David D.

    2012-01-01

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

  1. Entry time effects and follow-on drug competition.

    PubMed

    Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain

    2016-01-01

    Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one. PMID:25501258

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

    ERIC Educational Resources Information Center

    Elliott, Karen; Shelley, Kyna

    2006-01-01

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

  3. Positive Prevention: Successful Approaches To Preventing Youthful Drug and Alcohol Use [and] La Prevencion Positiva: Metodos que han tenido exito en la prevencion del uso de drogas y alcohol entre la juventud.

    ERIC Educational Resources Information Center

    American Association of School Administrators, Arlington, VA.

    The United States has the highest rate of youthful drug abuse of any industrialized country in the world. There is a growing awareness that drug and alcohol use are closely connected to other problems such as teenage suicide, adolescent pregnancy, traffic fatalities, juvenile delinquency, poor school performance, runaways, and dropouts. Youthful…

  4. Legalization of drugs of abuse and the pediatrician.

    TOXLINE Toxicology Bibliographic Information

    Schwartz RH

    1991-10-01

    Growing numbers of individuals are proposing that drugs be legalized in the United States, with claims that federal, state, and local efforts to prohibit the use of illicit drugs are irrational and unenforceable. "Drug reform" advocates include persons of all political persuasions. Ironically, the call for drug reform comes at a time when trends in drug abuse, as reflected in national and state surveys, show a promising decline. It also is contradictory to at least one recent public opinion poll, in which respondents opposed the legalization of marijuana by a five-to-one margin. While their position is by no means unanimous, proponents of drug reform generally base their arguments on several key premises, such as elimination of or reductions in drug trafficking, enforcement, and interdiction expenditures; increased tax revenues from the legal sale of drugs; and reductions in health-care expenses associated with drug treatment. Reform advocates further claim that legalization would not be followed by an increase in drug use. The validity of each of these arguments is highly questionable. Legalization is a simplistic, short-sighted solution to a complex issue with public health, economic, criminal justice, and societal ramifications. Legalization would, moreover, abrogate the position taken in 1961 by the United States and 114 other nations in ratifying the United Nations Single Convention on Narcotic Drugs. The impact of drug reform merits an unbiased study by an independent agency. Until that time, pediatricians should inform themselves of the arguments for and against drug reform and be prepared to educate patients and their families about the issue.

  5. Gender Differences in Psychopathy Links to Drug Use

    PubMed Central

    Schulz, Nicole; Murphy, Brett; Verona, Edelyn

    2015-01-01

    While the relationship between psychopathic personality traits and substance use has received some attention (Hart & Hare, 1989; Smith & Newman, 1990), gender differences have not been thoroughly assessed. The current study examined whether gender modified the relationship between two criminally-relevant constructs, a) psychopathy and its factors and b) drug use. A sample of 318 participants with criminal histories and recent substance use was assessed for psychopathy using the Psychopathy Checklist: Screening Version and for illicit drug use using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. As expected, the impulsive-antisocial traits (Factor 2) of psychopathy were positively related to a number of drug use characteristics (symptoms, age of drug initiation, extent of drug experimentation), whereas the interpersonal-affective traits (Factor 1) showed a negative relationship with drug abuse symptoms and a positive relationship with age of first use. In terms of gender differences, analyses revealed that women showed a stronger association between Factor 1 traits and later age of initiation compared to men, and that Factor 2, and antisocial facet in particular, were more strongly related to drug abuse in women than men. These findings suggest that psychopathic traits serve as both protective (Factor 1) and risk (Factor 2) correlates of illicit drug use, and in women, Factor 1 may be especially protective in terms of initiation. These conclusions add to the growing literature on potential routes to substance use and incarceration in women. PMID:26571339

  6. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  9. Drug diversion

    PubMed Central

    Wood, Danielle

    2015-01-01

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

  10. Rings in drugs.

    PubMed

    Taylor, Richard D; MacCoss, Malcolm; Lawson, Alastair D G

    2014-07-24

    We have analyzed the rings, ring systems, and frameworks in drugs listed in the FDA Orange Book to understand the frequency, timelines, molecular property space, and the application of these rings in different therapeutic areas and target classes. This analysis shows that there are only 351 ring systems and 1197 frameworks in drugs that came onto the market before 2013. Furthermore, on average six new ring systems enter drug space each year and approximately 28% of new drugs contain a new ring system. Moreover, it is very unusual for a drug to contain more than one new ring system and the majority of the most frequently used ring systems (83%) were first used in drugs developed prior to 1983. These observations give insight into the chemical novelty of drugs and potentially efficient ways to assess compound libraries and develop compounds from hit identification to lead optimization and beyond. PMID:24471928

  11. Position indicator

    DOEpatents

    Tanner, David E.

    1981-01-01

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

  12. The designer drug situation in Ibiza.

    PubMed

    Lora-Tamayo, C; Tena, T; Rodríguez, A; Moreno, D; Sancho, J R; Enseñat, P; Muela, F

    2004-03-10

    A total of 137 urine samples and 46 serum samples, corresponding to 154 self-confessed designer drugs consumers in Ibiza island, were analyzed for the presence of designer drugs: amphetamine and amphetamine derivatives (methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA), p-methoxymethylamphetamine (PMMA), p-methoxyamphetamine (PMA), etc.), ketamine and gamma-hydroxybutyric acid. Among this population, coming both from the forensic clinic and from the emergency room of a hospital, a total of 99 cases were found positive for some designer drug. This study shows the prevalence of methylenedioxymethamphetamine (MDMA) among designer drug users, sole or in association with other drugs. Also, the mixture of MDMA with other designer drugs, ethanol and/or cocaine is shown to be more likely to produce toxic symptoms requiring clinical attendance in a hospital emergency room. These findings along with the consumption history, the concentrations of drugs and metabolites in urine and serum and the toxicological significance for the interpretation of some MDMA metabolites such as 4-hydroxy-3-methoxymethamphetamine (HMMA) are discussed in this study. PMID:15036441

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

    PubMed

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

    2003-04-01

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

  14. Planning a Successful Tech Show

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2011-01-01

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

  15. Hey Teacher, Your Personality's Showing!

    ERIC Educational Resources Information Center

    Paulsen, James R.

    1977-01-01

    A study of 30 fourth, fifth, and sixth grade teachers and 300 of their students showed that a teacher's age, sex, and years of experience did not relate to students' mathematics achievement, but that more effective teachers showed greater "freedom from defensive behavior" than did less effective teachers. (DT)

  16. Planning a Successful Tech Show

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2011-01-01

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

  17. 21 CFR 1314.150 - Order To show cause.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Order To show cause. 1314.150 Section 1314.150... CHEMICAL PRODUCTS Order to Show Cause § 1314.150 Order To show cause. (a) If, upon information gathered by... upon the regulated seller or distributor an order to show cause why the regulated seller or...

  18. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

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

    PubMed Central

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

    2013-01-01

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

  20. Position sensor

    NASA Technical Reports Server (NTRS)

    Auer, Siegfried (Inventor)

    1988-01-01

    A radiant energy angle sensor is provided wherein the sensitive portion thereof comprises a pair of linear array detectors with each detector mounted normal to the other to provide X and Y channels and a pair of slits spaced from the pair of linear arrays with each of the slits positioned normal to its associated linear array. There is also provided electrical circuit means connected to the pair of linear array detectors and to separate X and Y axes outputs.

  1. Drug and Alcohol Involvement in Four Types of Fatal Crashes*

    PubMed Central

    Romano, Eduardo; Voas, Robert B.

    2011-01-01

    Objective: The aim of this study was to explore the relationship of drunk and drugged driving to the occurrence of fatal crashes associated with speeding, failure to obey/yield, inattention, and seat belt nonuse. Method: We examined data for fatally injured drivers involved in single-vehicle crashes killed in states in which more than 79% of the drivers were tested for drugs other than alcohol and had a known result. Results: About 25% of the drivers tested positive for drugs, a figure almost double that estimated by the 2007 National Roadside Survey. Cannabinoids and stimulants each contributed to about 23% of the drug-positive results (6% among all fatally injured single-vehicle drivers). Stimulants more than cannabinoids were found to be associated with the four types of crashes under study. Some drugs showed a protective effect over the four crash types under study. Significant interactions between drugs and alcohol were observed. Stimulants contributed to the different types of fatal crashes irrespective of the levels of alcohol consumed by the drivers. Conclusions: This study provides further evidence of a link between drug consumption and fatal crashes. It also opens the door to some interesting and sometimes unexpected questions regarding the way drugs contribute to crashes, which we found varies depending on the type of crash considered, the class of drug, and the presence of alcohol. Research is also needed on drugs that could have a protective effect on the occurrence of fatal crashes. These findings could be highly relevant to the design of drug-related traffic laws and programs targeted at curbing drugged driving. PMID:21683038

  2. Deuterated Drugs.

    PubMed

    Howland, Robert H

    2015-09-01

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

  3. National Orange Show Photovoltaic Demonstration

    SciTech Connect

    Dan Jimenez Sheri Raborn, CPA; Tom Baker

    2008-03-31

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

  4. Positive Psychologists on Positive Constructs

    ERIC Educational Resources Information Center

    Lyubomirsky, Sonja

    2012-01-01

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

  5. Comparison of Attitudes, Knowledge and Drug Abuse Among Military Offenders

    ERIC Educational Resources Information Center

    Ratliff, Bascom W.

    1977-01-01

    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.…

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  8. Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells

    PubMed Central

    Pu, Yingying; Zhao, Zhilun; Li, Yingxing; Zou, Jin; Ma, Qi; Zhao, Yanna; Ke, Yuehua; Zhu, Yun; Chen, Huiyi; Baker, Matthew A.B.; Ge, Hao; Sun, Yujie; Xie, Xiaoliang Sunney; Bai, Fan

    2016-01-01

    Summary Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under β-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance. PMID:27105118

  9. Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells.

    PubMed

    Pu, Yingying; Zhao, Zhilun; Li, Yingxing; Zou, Jin; Ma, Qi; Zhao, Yanna; Ke, Yuehua; Zhu, Yun; Chen, Huiyi; Baker, Matthew A B; Ge, Hao; Sun, Yujie; Xie, Xiaoliang Sunney; Bai, Fan

    2016-04-21

    Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under β-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance. PMID:27105118

  10. Drug Impact Index.

    ERIC Educational Resources Information Center

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  11. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    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)

  12. Drug Facts

    MedlinePlus Videos and Cool Tools

    ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine ( ... Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can ...

  13. Prescription Drugs

    MedlinePlus

    ... Heads Up: Real News About Drugs and Your Body Mind Over Matter Series Explorando la Mente Serie Blog ... Heads Up: Real News About Drugs and Your Body Mind Over Matter Series Explorando la Mente Serie Blog ...

  14. Drugged Driving

    MedlinePlus

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

  15. Drugged Driving

    MedlinePlus

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

  16. Positioning apparatus

    DOEpatents

    Vogel, Max A.; Alter, Paul

    1986-01-01

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

  17. POSITIONING DEVICE

    DOEpatents

    Wall, R.R.; Peterson, D.L.

    1959-09-15

    A positioner is described for a vertical reactor-control rod. The positioner comprises four grooved friction rotatable members that engage the control rod on all sides and shift it longitudinally. The four friction members are drivingly interconnected for conjoint rotation and comprise two pairs of coaxial members. The members of each pair are urged toward one another by hydraulic or pneumatic pressure and thus grip the control rod so as to hold it in any position or adjust it. Release of the by-draulic or pneumatic pressure permits springs between the friction members of each pair to force them apart, whereby the control rod moves quickly by gravity into the reactor.

  18. Positioning apparatus

    DOEpatents

    Vogel, M.A.; Alter, P.

    1983-07-07

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

  19. Magic Carpet Shows Its Colors

    NASA Technical Reports Server (NTRS)

    2004-01-01

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

  20. 21 CFR 1301.37 - Order to show cause.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Order to show cause. 1301.37 Section 1301.37 Food... Suspension of Registration § 1301.37 Order to show cause. (a) If, upon examination of the application for... Administrator shall serve upon the applicant an order to show cause why the registration should not be...

  1. 21 CFR 1309.46 - Order to show cause.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Order to show cause. 1309.46 Section 1309.46 Food... Or Suspension of Registration § 1309.46 Order to show cause. (a) If, upon examination of the... upon the applicant an order to show cause why the application for registration should not be denied....

  2. 21 CFR 1309.46 - Order to show cause.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Order to show cause. 1309.46 Section 1309.46 Food... Or Suspension of Registration § 1309.46 Order to show cause. (a) If, upon examination of the... upon the applicant an order to show cause why the application for registration should not be denied....

  3. 21 CFR 1301.37 - Order to show cause.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Order to show cause. 1301.37 Section 1301.37 Food... Suspension of Registration § 1301.37 Order to show cause. (a) If, upon examination of the application for... Administrator shall serve upon the applicant an order to show cause why the registration should not be...

  4. ENVITEC shows off air technologies

    SciTech Connect

    McIlvaine, R.W.

    1995-08-01

    The ENVITEC International Trade Fair for Environmental Protection and Waste Management Technologies, held in June in Duesseldorf, Germany, is the largest air pollution exhibition in the world and may be the largest environmental technology show overall. Visitors saw thousands of environmental solutions from 1,318 companies representing 29 countries and occupying roughly 43,000 square meters of exhibit space. Many innovations were displayed under the category, ``thermal treatment of air pollutants.`` New technologies include the following: regenerative thermal oxidizers; wet systems for removing pollutants; biological scrubbers;electrostatic precipitators; selective adsorption systems; activated-coke adsorbers; optimization of scrubber systems; and air pollution monitors.

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

    NASA Astrophysics Data System (ADS)

    Bhunu, C. P.

    2014-06-01

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

  6. Who Tests which Athletes for What Drugs?

    ERIC Educational Resources Information Center

    Gall, Sarah L.; And Others

    1988-01-01

    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)

  7. [Newer antiepileptic drugs].

    PubMed

    Matsuura, Masato

    2007-02-01

    Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and dropout rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine, oxycarbazepine, etc.), or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection. PMID:17380779

  8. [Newer antiepileptic drugs].

    PubMed

    Matsuura, Masato

    2007-02-01

    Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and drop-out rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine, oxycarbazepine, etc.), or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection. PMID:17315756

  9. ShowMe3D

    Energy Science and Technology Software Center (ESTSC)

    2012-01-05

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

  10. Phoenix Scoop Inverted Showing Rasp

    NASA Technical Reports Server (NTRS)

    2008-01-01

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

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

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

  11. ShowMe3D

    SciTech Connect

    Sinclair, Michael B

    2012-01-05

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

  12. [Drug deaths].

    PubMed

    Gerber, A

    1976-01-01

    In the Federal Republic of Germany there exist no statistical datas concerning death related to drug dependence until now. We propose to define death in connexion with drug dependence as the death of a drug dependent person caused by direct or indirect effect of the drug used. We first report on several international investigations; then the results of our own investigation in 40 cases of death in connexion with drug dependence in the district of Nordbaden are presented in detail. As a result it seems necessary to register drug dependent persons and to isolate those who are resistent to any therapy and thus represent a focus for further expansion of drug consuming. PMID:962461

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

    PubMed Central

    Zeng, Hui; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. Database URL: http://www.cuilab.cn/drugpath PMID:26130661

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

    PubMed

    Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. PMID:26130661

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  16. Patents Associated with High-Cost Drugs in Australia

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

    2013-01-01

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

  18. Casimir experiments showing saturation effects

    SciTech Connect

    Sernelius, Bo E.

    2009-10-15

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

  19. Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures

    PubMed Central

    Lee, Haeseung; Kang, Seungmin; Kim, Wankyu

    2016-01-01

    An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug’s mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity. PMID:26954019

  20. GWAS and drug targets

    PubMed Central

    2014-01-01

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

  1. [Value of positive auto controls in the gel centrifugation method].

    PubMed

    Eichler, H; Kretschmer, V

    1994-01-01

    We studied 97 samples of patients being positive in the autocontrol of the indirect antiglobulin test (IAT) in the gel system (DiaMed). In 83.2%, retesting with monospecific anti-IgG serum gave also positive results, due to a specific phenomenon caused, for example, by drug-specific antibodies (AB), warm auto-AB or allo-AB. In contrast, only 52.9% of the samples retested by the standard tube technique with polyspecific antiglobulin serum reacted positive. Only in 6 patients slightly increased cold agglutinins could be detected. None of the investigated patients showed any clinical or laboratory signs of hemolysis except one with pernicious anemia. We conclude that positive results of the autocontrol in the gel IAT should be confirmed by an additional DAT in the tube technique. If this second test shows a negative result, transfusions can take place without any restrictions. PMID:9480074

  2. Marijuana and Children. Position Statement

    ERIC Educational Resources Information Center

    Endsley, Patricia; Embrey, Mary Louise

    2014-01-01

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

  3. 21 CFR 880.5680 - Pediatric position holder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pediatric position holder. 880.5680 Section 880.5680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5680 Pediatric position...

  4. Characteristics of injection drug users who participate in drug dealing: implications for drug policy.

    PubMed

    Kerr, Thomas; Small, William; Johnston, Caitlin; Li, Kathy; Montaner, Julio S G; Wood, Evan

    2008-06-01

    So-called "balanced" drug policy couples enforcement initiatives targeting drug dealers with health-focused interventions serving addicted individuals. There are few evaluations of this approach, and little is known about how these two populations may overlap. We evaluated factors associated with drug dealing among injection drug users (IDUs) in Vancouver, Canada, and examined self-reported drug-dealing roles and reasons for dealing. Among 412 IDUs seen from March through December 2005, 68 (17%) had dealt drugs during the previous six months. Variables independently associated with drug dealing included: recent incarceration (adjusted odds ratio [AOR] = 2.9; 95%CI: 1.4-6.0); frequent heroin injection (AOR = 2.5; 95%CI: 1.4-4.6); frequent cocaine injection (AOR = 2.0; 95%CI: 1.1-3.8); and recent overdose (AOR = 2.7; 95%CI: 1.0-7.3). The most common drug-dealing roles were direct selling (82%), middling (35%), and steering (19%), while the most common reasons for dealing included obtaining drugs (49%) and money (36%). Drug dealing among IDUs was predicted by several markers of higher intensity addiction, and drug-dealing IDUs tended to occupy the most dangerous positions in the drug-dealing hierarchy. These findings suggest that elements of "balanced" drug policies may undermine each other and indicate the need for alternative interventions. PMID:18720663

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

    SciTech Connect

    Charalambous, Christiana; Virrey, Jenilyn; Kardosh, Adel; Jabbour, Mark N.; Qazi-Abdullah, Lubna; Pen, Ligaya; Zidovetzki, Raphael; Schoenthal, Axel H.; Chen, Thomas C.; Hofman, Florence M. . E-mail: hofman@usc.edu

    2007-04-01

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

  6. Qualitative measurement of drugs.

    PubMed

    Westerman, S T; Golz, A; Komorowski, F S; Gilbert, L M

    1984-02-01

    It has been noted for several years that certain drugs produce abnormal test results in patients who are administered the electronystagmograph (ENG) test. Drug specific waveforms, termed drug evoked potentials (DEP), have been identified by using the ENG for alcohol, marijuana, cocaine, tranquilizers, amphetamines, barbiturates, opiates, hallucinogens, caffeine, aminophylline, dopamine, several gases and approximately 75 combinations of drugs (N = 821). Tests for double blind diagnosis of drug intake as well as tests for repeatability within the same subject were conducted. Subjects included surgical candidates, healthy volunteers, and neonates (N = 248). Drugs tested were ketamine hydrochloride, fentanyl, sodium pentothal, cocaine, dextroamphetamine, sodium seconal, morphine sulfate, phenobarbital, and meperidine. Placebos of dextrose in water and sucrose tablets were also used (N = 25). Analysis of the waveforms produced by surgical candidates and healthy volunteers revealed no false negatives or false positives. Analysis of waveforms produced by neonates whose mothers had been administered meperidine demonstrated a diminishing effect over the course of a 3 day period. Results of repeated studies revealed reliability within subject. One subject who was administered dextroamphetamine did not produce a wave consistent with amphetamine with a dosage of 5 mg. He did, however, produce an amphetamine wave when administered 10 mg of dextroamphetamine. These findings suggest a dose related effect, indicating the need for establishment of minimal levels of detection. Results indicate that with refinement and further research, this method could be used for identification of drugs diagnostically. PMID:6694484

  7. Positivity of Quasilocal Mass

    NASA Astrophysics Data System (ADS)

    Liu, Chiu-Chu Melissa; Yau, Shing-Tung

    2003-06-01

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

  8. Alcohol, Drugs and Young Drivers.

    ERIC Educational Resources Information Center

    Voas, Robert B.

    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…

  9. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

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

  10. Drug shortage.

    PubMed

    Conde, Crystal

    2011-10-01

    Calcium gluconate, neostigmine, propofol, epinephrine, furosemide, and a host of sterile injectables, as well as antibiotics and other medications, are among the drugs on an expansive list of shortages tracked by the U.S. Food and Drug Administration (FDA). A record 246 drugs were in short supply as of June, according to FDA. That figure has many Texas physicians worried about potential risks to patient safety and quality of care. PMID:21971836

  11. [Drugs cardiotoxicity].

    PubMed

    Capilla, Eléonore; Poyet, Raphael; Brocq, Francois-Xavier; Pons, Frédéric; Kerebel, Sébastien; Jego, Christophe; Laurent, Pierre; Cellarier, Gilles Rolland

    2015-10-01

    Thanks to science advances, cancer is no longer synonymous with death. Life expectancy improvement reveals a new problem: cancer treatment toxicity, including cardiovascular complications, responsible for significant morbidity and mortality. Media scandal of drug-induced valvular heart disease did revise the risk-benefit balance of drugs used (often off-label) as anorectics. Today's society uses drugs heavily but does not accept their side effects. Knowledge and information of these complications is essential. Coronary toxicity of some treatments or drugs commonly used must be known. PMID:26153088

  12. Influences of Motivational Contexts on Prescription Drug Misuse and Related Drug Problems

    PubMed Central

    Kelly, Brian C.; Rendina, H. Jonathon; Vuolo, Mike; Wells, Brooke E.; Parsons, Jeffrey T.

    2014-01-01

    Prescription drug misuse has emerged as a significant problem among young adults. While the effects of motivational contexts have been demonstrated for illicit drugs, the role of motivational contexts in prescription drug misuse remains understudied. Using data from 400 young adults recruited via time-space sampling, we examined the role of motivational contexts in the frequency of misuse of three prescription drug types as well as drug-related problems and symptoms of dependency. Both negative and positive motivations to use drugs are associated with increases in prescription drug misuse frequency. Only negative motivations are associated directly with drug problems and drug dependence, as well as indirectly via prescription pain killer misuse. Addressing positive and negative motivational contexts of prescription drug misuse may not only provide a means to reduce misuse and implement harm reduction measures, but may also inform the content of treatment plans for young adults with prescription drug misuse problems. PMID:25115134

  13. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics. PMID:22805763

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

    PubMed Central

    Kurzban, Robert; Dukes, Amber; Weeden, Jason

    2010-01-01

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

  15. [Drug dependence and psychotropic drugs].

    PubMed

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

    1994-11-01

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

  16. Voice of the psychonauts: coping, life purpose, and spirituality in psychedelic drug users.

    PubMed

    Móró, Levente; Simon, Katalin; Bárd, Imre; Rácz, József

    2011-01-01

    Psychoactive drug use shows great diversity, but due to a disproportionate focus on problematic drug use, predominant nonproblematic drug use remains an understudied phenomenon. Historic and anecdotal evidence shows that natural sources of "psychedelic" drugs (e.g., mescaline and psilocybin) have been used in religious and spiritual settings for centuries, as well as for psychological self-enhancement purposes. Our study assessed a total of 667 psychedelic drug users, other drug users, and drug nonusers by online questionnaires. Coping, life purpose, and spirituality were measured with the Psychological Immune Competence Inventory, the Purpose in Life test, and the Intrinsic Spirituality Scale, respectively. Results indicate that the use of psychedelic drugs with a purpose to enhance self-knowledge is less associated with problems, and correlates positively with coping and spirituality. Albeit the meaning of "spirituality" may be ambiguous, it seems that a spiritually-inclined attitude in drug use may act as a protective factor against drug-related problems. The autognostic use of psychedelic drugs may be thus hypothesized as a "training situation" that promotes self-enhancement by rehearsing personal coping strategies and by gaining self-knowledge. However, to assess the actual efficiency and the speculated long-term benefits of these deliberately provoked exceptional experiences, further qualitative investigations are needed. PMID:22111402

  17. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

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

  18. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

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

  19. Interoception and Drug Addiction

    PubMed Central

    Paulus, Martin P.; Stewart, Jennifer L.

    2013-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an “embodied” experience of drug uses together with the individual’s predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. PMID:23855999

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

    PubMed Central

    D'Souza, Manoranjan S.

    2015-01-01

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

  1. Evaluation of drug interactions with nanofibrillar cellulose.

    PubMed

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

    2013-11-01

    Nanofibrillar cellulose (NFC) (also referred to as cellulose nanofibers, nanocellulose, microfibrillated, or nanofibrillated cellulose) has recently gotten wide attention in various research areas and it has also been studied as excipient in formulation of the pharmaceutical dosage forms. Here, we have evaluated the interactions between NFC and the model drugs of different structural characteristics (size, charge, etc.). The series of permeation studies were utilized to evaluate the ability of the drugs in solution to diffuse through the thin, porous, dry NFC films. An incubation method was used to determine capacity of binding of chosen model drugs to NFC as well as isothermal titration calorimetry (ITC) to study thermodynamics of the binding process. A genetically engineered fusion protein carrying double cellulose binding domain was used as a positive control since its affinity and capacity of binding for NFC have already been reported. The permeation studies revealed the size dependent diffusion rate of the model drugs through the NFC films. The results of both binding and ITC studies showed that the studied drugs bind to the NFC material and indicated the pH dependence of the binding and electrostatic forces as the main mechanism. PMID:23774185

  2. Nanotopography applications in drug delivery

    PubMed Central

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

    2016-01-01

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

  3. Neural Effects of Positive and Negative Incentives during Marijuana Withdrawal

    PubMed Central

    Filbey, Francesca M.; Dunlop, Joseph; Myers, Ursula S.

    2013-01-01

    In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms. PMID:23690923

  4. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug release property to achieve increased therapeutic efficacy and reduced side effects. Nanoparticles and nanoliposomes are emerging areas of nanotechnologies that have already begun to make an impact over new modalities for cancer chemotherapy, diagnosis as well as gene delivery. Presently it is possible to reduce the particle size in such a way that the particles can be easily injected or inhaled and many types of human cells are capable to internalize them. A number of fabrications such as PEGylation, specific antibody conjugation, aptamer ligation, specific ligand binding etc. on the nanosize delivery devices makes them in the streamline of research to particularly target the diseased cells thus avoiding the healthy one. Potential of nanosize carriers to cross the blood brain barrier encourages us to build up a new strategy for delivery of therapeutically active agents to the brain. Nanotechnology is showing an emerging effect in chronic diseases such as diabetes, cancer, neurodegenerative diseases etc. Nanosize vaccines are having greater effect in production of better immunity against pathogens through direct administration of medication to the specialized dendritic cells in the immune systems. Lots of hopes and speculations are reigning around the scientists with nanosize drug delivery systems that may revolutionize the drug delivery with the better understanding of drug action mechanism and identification of biomarker associated with specific diseases. Nanosize drug delivery systems are emerging with the promising strategies for efficient targeted drug delivery. The proper designing of these systems can make them capable for being independent in the normal tissue environments and selective at the diseased pharmacological site. Nanomaterials as formulations are already in the market or in clinical trials. Investigation on nanostructural drug delivery is a highly growing field today as an extensive amount of research is on with an expectation to open up new avenues to drug delivery. No doubt the next era of drug therapy will be greater influenced by nanoscale drug delivery systems. However these newer systems for delivery of bioactive molecules must be reliable, efficient and safe. PMID:25106648

  5. Educational Outreach: The Space Science Road Show

    NASA Astrophysics Data System (ADS)

    Cox, N. L. J.

    2002-01-01

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

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

    PubMed Central

    Peetla, Chiranjeevi; Vijayaraghavalu, Sivakumar; Labhasetwar, Vinod

    2013-01-01

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

  7. Discontinued drugs in 2012: cardiovascular drugs.

    PubMed

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

    2013-11-01

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

  8. [Alexithymia, depression and drug addiction].

    PubMed

    F farges; Corcos, M; Speranza, M; Loas, G; Perez-Diaz, F; Venisse, J-L; Lang, F; Bizouard, P; Halfon, O; Flament, M; Jeammet, Ph

    2004-01-01

    Alexithymia is a multidimensional concept associating an emotional component focused on the difficulty in identifying and describing feelings and a cognitive one centred on the use of a concrete and poorly introspective way of thinking. Alexithymia can be assessed by self-assessment instruments and in particular by the 20 items version of the Toronto Alexithymia Scale (TAS-20). Depressive disorders have complex relationships with the construct of alexithymia and there exist few experimental works on the subject. Epidemiological studies frequently raise an overlap between alexithymia and depression, in particular in the context of addiction. The main aim of this study was to confirm the high prevalence of alexithymia among drug addicted patients taking into account socio-demographic variables (sex, age, social and economic categories). The second aim of the study was to investigate the relationships between alexithymia and depression among drug addicted patients. A sample of 128 drug addicted patients answering DSM IV criteria of dependence to a psycho-active substance (alcohol excluded) was paired according to socio-demographic variables to a control sample of 128 normal subjects. Diagnostic assessment was made using the Mini International Neuropsychiatric Interview (MINI). Alexithymia and depression were assessed with the TAS-20 and with the short version of the Beck Depression Inventory (BDI-13). The results confirm the high prevalence of alexithymia among drug addicted patients (43.5%) compared to controls (24.6%). This difference is based namely on the emotional component of alexithymia, the cognitive component failing to show any difference between the two samples. Moreover, alexithymia appears to be independent from socio-demographic variables in our sample of drug addicted patients; 66.4% of drug addicted patients presents a depressive symptomatology (which is significantly more important in female patients), compared to 26% of the controls. Studies using the TAS and the BDI with 21 items have shown that from 10 to 20% of the variance of alexithymia is explained by depression. Our own results show a shared variance of 20% between the TAS-20 and the BDI, going in the direction of a moderated correlation between alexithymia and depressive symptomatology. Moreover, when we retain only subjects without depressive symptomatology at BDI, drug addicted (n=42) are not any more alexithymic than controls (n=114). Our results plead for a positive association between depression and alexithymia in drug addicted, depressed or healthy subjects. Alexithymia and depression would be two associated dimensions, the emotional component explaining alone this association. The emotional component of the alexithymia would be thymo-dependent, whereas the cognitive component (externally oriented thought) would be independent and constitute a stable clinical feature. These results are concordant with other studies in the literature suggesting that alexithymia in its emotional component is supported by depression. Alexithymia thus did not appear as an autonomous dimension which would discriminate between drug addicted and controls, independently of the absence of a depressive state. The Authors discuss the complexity of the relationships between alexithymia and depression and the correlations between TAS and BDI scales especially for the factor Difficulty Identifying Feelings. These results deserve further studies. The cross-sectional nature of this study do not allow to establish if alexithymia is a subjacent and preexistent in the form of a psychopathological dimension in addictive behaviours, so supporting its emergence, and/or if it develops once the dependence is installed and chronicized. Longitudinal studies remain to be realised. PMID:15235517

  9. Tunable drug loading and release from polypeptide multilayer nanofilms

    PubMed Central

    Jiang, Bingbing; Li, Bingyun

    2009-01-01

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

  10. Drug Reactions

    MedlinePlus

    ... and grapefruit juice, as well as alcohol and caffeine, may affect how drugs work. Every time your ... notice during a check-up: Changes in lab test results Abnormal heartbeat What will my doctor do if ...

  11. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  12. Micro-Fluidic Device for Drug Delivery

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  13. [Is drug advertising reliable?].

    PubMed

    Spigset, O

    1998-12-10

    In order to assess the quality of pharmaceutical advertising in Norway, we conducted a review of advertisements for selective serotonin re-uptake inhibitors published in the Journal of the Norwegian Medical Association and the journal Legemidler og samfunn during the period 1995-97. 18 advertisements with 38 reference citations were identified. In six citations (16%), errors made it impossible to identify the source with certainty solely on the basis of the advertisement. Under Norwegian drug advertisement regulations, a total of 56 statements should have been followed by a reference citation. In 18 of these (33%), it was debatable whether the statements were in accordance with the regulations. This review indicates that a significant proportion of the statements in drug advertisements is inaccurate and gives a too positive picture of the properties of the drug. PMID:9914744

  14. Bioequivalence of generic drugs.

    PubMed

    Andrade, Chittaranjan

    2015-09-01

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

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

    PubMed Central

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

    2010-01-01

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

  16. A randomized pilot study of the Engaging Moms Program for family drug court.

    PubMed

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

    2010-04-01

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

  17. 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

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

    PubMed Central

    Lee, Kye Hwa; Kim, Grace Juyun

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2014-01-01

    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

  1. Studies Of Positive-Position-Feedback Control

    NASA Technical Reports Server (NTRS)

    Fanson, James L.; Caughey, Thomas K.

    1992-01-01

    Report discusses theoretical and experimental studies of positive-position-feedback control for suppressing vibrations in large flexible structures. Positive-position-feedback control involves placement of actuators and sensors on structure; control voltages applied to actuators in response to outputs of sensors processed via compensator algorithm. Experiments demonstrate feasibility of suppressing vibrations by positive position feedback, and spillover of vibrational energy into uncontrolled modes has stabilizing effect if control gain sufficiently small.

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

    ERIC Educational Resources Information Center

    Office of National Drug Control Policy, 2007

    2007-01-01

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

  3. Bacteriophages show promise as antimicrobial agents.

    PubMed

    Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N

    1998-01-01

    The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed papers is provided. PMID:9515662

  4. Spirit Wiggles into Position

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Spirit completed a difficult, rocky ascent en route to reaching a captivating rock outcrop nicknamed 'Hillary' at the summit of 'Husband Hill.' At the end of the climb the robotic geologist was tilted almost 30 degrees. To get the rover on more solid footing for deploying the instrument arm, rover drivers told Spirit to wiggle its wheels one at a time. This animation shows Spirit's position before and after completing the wheel wiggle, during which the rover slid approximately 1 centimeter (0.4 inch) downhill. Rover drivers decided this position was too hazardous for deploying the instrument arm and subsequently directed Spirit to a more stable position before conducting analyses with instruments on the rover's arm.

    Spirit took these images with its front hazard-avoidance camera on martian day, or sol, 625 (Oct. 6, 2005).

  5. Show Horse Welfare: The Viewpoints of Judges, Stewards, and Show Managers.

    PubMed

    Voigt, Melissa; Hiney, Kristina; Croney, Candace; Waite, Karen; Borron, Abigail; Brady, Colleen

    2016-01-01

    The purpose of this study was to gain a better understanding of the current state of stock-type show horse welfare based on the perceptions of show officials and to identify potential means of preventing and intervening in compromises to show horse welfare. Thirteen horse show officials, including judges, stewards, and show managers, were interviewed. Findings revealed the officials had an incomplete understanding of nonhuman animal welfare and a high level of concern regarding the public's perception of show horse welfare. The officials attributed most of the frequently observed compromises to show horse welfare to (a) novices', amateurs', and young trainers' lack of experience or expertise, and (b) trainers' and owners' unrealistic expectations and prioritization of winning over horse welfare. The officials emphasized a need for distribution of responsibility among associations, officials, and individuals within the industry. Although the officials noted recent observable positive changes in the industry, they emphasized the need for continued improvements in equine welfare and greater educational opportunities for stakeholders. PMID:26742585

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

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

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

  7. RIVER AND ROAD VIEW SHOWING METAL CRIB RETAINING WALLS AT ...

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

    RIVER AND ROAD VIEW SHOWING METAL CRIB RETAINING WALLS AT RIGHT, FACING SOUTHWEST. PHOTO IS TAKEN FROM SAME POSITION AS PHOTO NO. 84, BUT WITH LONG LENS - Generals Highway, Three Rivers, Tulare County, CA

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

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

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

  9. 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

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2014-09-01

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

  12. Anthelmintic drugs.

    PubMed Central

    Holden-Dye, Lindy; Walker, Robert J

    2007-01-01

    C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity to use molecular genetic techniques in the worm for mode of action studies. These approaches continue to be of considerable value to the field of parasitology. In addition, there are numerous examples of anthelmintic drugs providing exceptionally useful pharmacological tools to delineate fundamental aspects of cell signalling in C. elegans. This has primarily been achieved through the use of anthelmintics in forward genetic screens followed by the mapping and characterization of genes that confer altered susceptibility to the drug. Less fruitful so far, but nonetheless useful, has been the direct use of C. elegans for anthelmintic discovery programmes. In this brief review we provide an introduction to the use of C. elegans as a 'model parasite', outline the actions of the main classes of anthelmintics, and highlight approaches that have been of particular value. PMID:17988075

  13. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

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

  14. AIDSinfo Drug Database

    MedlinePlus

    ... related drugs for health care providers and patients. Search the Drug Database Help × Search by drug name Performs a search by drug ... common names of the drug. Drug Class: Help × Search by drug class Select a specific drug class ...

  15. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    PubMed Central

    Lee, Jinsoo; Son, Kwanghyun; Hwang, Gwiseo

    2016-01-01

    Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT) has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p = 0.0284, Fisher's exact test). Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children. PMID:27047568

  16. Teenagers and drugs

    MedlinePlus

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

  17. Temperature Data Shows Warming in 2001

    NASA Technical Reports Server (NTRS)

    2002-01-01

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

  18. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  19. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  20. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  1. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  2. 21 CFR 890.3110 - Electric positioning chair.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. Prescription Drugs

    MedlinePlus

    ... factors interact and put them at risk. Personal information. Doctors take into account a person's weight, how long they've been prescribed the medication, and what other medications they are taking. Someone abusing prescription drugs may overload their system or put themselves at risk for ...

  4. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

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

  5. Drug Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Drug resistance refers to both intrinsic and acquired abilities of cells or organisms to become insensitive or refractory to chemotherapeutic intervention. The advent of antibiotics is considered one of the most important medicinal developments in human history, which has led to significantly reduce...

  6. Club Drugs

    MedlinePlus

    ... include Methylenedioxymethamphetamine (MDMA), also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known as Roofies ...

  7. Generic Drugs

    MedlinePlus

    ... drug Cost per month Generic substitute Glucotrol 10mg tablet $42– $84 Glipizide 10mg tablet Coreg 12.5mg $166 Carvedilol 12.5mg Zocor 20mg $175 Simvastatin 20mg Imitrex 25mg tablet $78 Sumatriptan 25mg tablet Cost per month $4–$ ...

  8. Identifying drug-abusing criminals.

    PubMed

    Wish, E D

    1988-01-01

    In a criminal justice setting, urine testing is the most feasible and accurate method now available for screening large numbers of drug-using offenders. Self-report and record information can be effectively used to verify and extend information about the seriousness of use for those who test positive. The newer RIAH methods offer promise for delineating patterns of drug use over time if the method is valid, can be standardized, and gains acceptance from the scientific and judicial communities. PMID:3140028

  9. Benign positional vertigo - aftercare

    MedlinePlus

    Vertigo - positional - aftercare; Benign paroxysmal positional vertigo - aftercare; BPPV - aftercare ... Bronston LJ, Cass S, et al. Clinical practice guideline: Benign paroxysmal positional vertigo. Otolaryngology - Head and Neck Surgery . ...

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

    PubMed

    Couto, Mariana; Silva, Diana; Ferreira, Ana; Cernadas, Josefina R

    2014-09-01

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

  11. Positive position control of robotic manipulators

    NASA Technical Reports Server (NTRS)

    Baz, A.; Gumusel, L.

    1989-01-01

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

  12. Significant drug-nutrient interactions.

    PubMed

    Kirk, J K

    1995-04-01

    Many nutrients substantially interfere with pharmacotherapeutic goals. The presence of certain nutrients in the gastrointestinal tract affects the bioavailability and disposition of many oral medications. Drug-nutrient interactions can also have positive effects that result in increased drug absorption or reduced gastrointestinal irritation. Knowing the significant drug-nutrient interactions can help the clinician identify the nutrients to avoid with certain medications, as well as the therapeutic agents that should be administered with food. This information can be used to educate patients and optimize pharmacotherapy. PMID:7709893

  13. Survey Shows Brighter Outlook for Older Executives.

    ERIC Educational Resources Information Center

    Cronin, Carol A.

    1982-01-01

    A survey of the leading executive search firms indicates an increased willingness to consider older personnel for top positions--particularly at the executive level. Factors affecting this more positive outlook include changed attitudes toward older people in general and the importance of experience as an issue in selection. (Author/SK)

  14. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    2001-01-01

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

  15. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    1998-10-01

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

  16. Prevalence of psychotropic drug use in military police units.

    PubMed

    Costa, Srgio Henrique Nascente; Yonamine, Maurcio; Ramos, Andrea Luciana Martins; Oliveira, Fernando Gomes Ferreira; Rodrigues, Caroline Rego; da Cunha, Luiz Carlos

    2015-06-01

    The present study aimed to verify the prevalence of psychoactive drug use (amphetamines, methamphetamines, cannabinoids, cocaine, opioids and benzodiazepines) among military police officers in the state of Gois. Data were obtained from urine samples voluntarily provided by the officers participating in the study, who were informed of the study methods and signed a free and informed consent form. The samples were subject to screening analysis by immunochromatography (Multi-DrugOneStep Test), with positive tests confirmed by gas chromatography- mass spectrometry (GC-MS) and data analyzed by descriptive statistics. The results indicated the presence of the following drugs: amphetamines (0.33%), cannabinoids (0.67%) and benzodiazepines (1.34%); 97.66% showed negative results. The positive cases were distributed as follows: benzodiazepines (57.1%); cannabinoids (28.6%) and amphetamines (14.3%). In conclusion, the detection of psychoactive substances in voluntary sampling of military police officers indicates the need to implement drug testing among active military officers and preventive public policies aimed at eliminating the abusive consumption of psychotropic drugs. PMID:26060962

  17. Can aging be 'drugged'?

    PubMed

    Riera, Celine E; Dillin, Andrew

    2015-12-01

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

  18. Environmental Effects on Drug Use

    ERIC Educational Resources Information Center

    Russell, James A.; Mehrabian, Albert

    1977-01-01

    Emotional impact of various stimulant and depressant drugs is reviewed and emotional impact of various types of environments is described. Emotional predispositions associated with personality are noted. Specific hypotheses are derived to show which drugs are most likely to be used in different, environmentally induced or temperament-associated,…

  19. In silico modeling to predict drug-induced phospholipidosis

    SciTech Connect

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

    2013-06-01

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

  20. Multiple prescriptions and drug appropriateness.

    PubMed Central

    Miles, D L

    1977-01-01

    The relationship between number of prescriptions per office visit and the appropriateness of the prescribed drugs is examined, using data on more than 20,000 prescriptions purchased for a low-income rural population during 1973 and 1974. Criteria for drug appropriateness are based on an AMA evaluation of drugs. The results show that greater numbers of prescriptions per visit are associated with lower percentages of appropriate drugs prescribed and that patients whose prescriptions were written by specialists received a higher percentage of appropriate drugs than did those whose prescriptions were written by general practitioners. It is concluded, in support of other researchers, that a better knowledge of drugs leads to more conservative use of them. PMID:873813

  1. Drug-induced peripheral neuropathies.

    PubMed Central

    Argov, Z; Mastaglia, F L

    1979-01-01

    Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely. PMID:219931

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

    PubMed Central

    2010-01-01

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

  3. Drug models of schizophrenia.

    PubMed

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

    2015-02-01

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

  4. Drug models of schizophrenia

    PubMed Central

    Steeds, Hannah; Carhart-Harris, Robin L.

    2015-01-01

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

  5. Compulsory licensing and access to drugs.

    PubMed

    Stavropoulou, Charitini; Valletti, Tommaso

    2015-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

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

    PubMed

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

    2014-07-11

    In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4'-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes' stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats' retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes. PMID:24960297

  8. Photomechanical drug delivery

    NASA Astrophysics Data System (ADS)

    Doukas, Apostolos G.; Lee, Shun

    2000-05-01

    Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

  9. Drug addiction in pregnancy.

    PubMed

    Fraser, A C

    1976-10-23

    32 pregnancies in 29 drug-addicted women were studied ouver eight years in one obstetric department working in close liaison with a drug dependency centre. Of the 24 pregnancies which came to term, only 10 were seen at the antenatal clinic before 22 weeks' gestation. 19 of the women were addicted to heroin or methadone or a mixture of both, 4 were taking soft drugs, and 1 was taking pethidine only. Labour commenced spontaneously in 17 pregnancies and was induced in 7. All labours lasted less than twenty hours. 23 infants survived. Those born to the mother taking pethidine and to 4 mothers who withdrew their drug of dependence four weeks before delivery showed no signs of narcotic withdrawal, but 13 out of 14 infants born to mothers taking heroin or methadone developed narcotic withdrawal syndrome. It is recommended that drug therapy during pregnancy in addicts should be supervised by a psychiatrist known to the patient and that oral methadone be substituted for heroin. Planned induction will ensure delivery in hospital, at the hospital which has supervised the pregnancy. Babies in danger of developing narcotic withdrawal syndrome should be observed in the special care baby unit for the first week of life. PMID:62125

  10. Diagnosing Dementia—Positive Signs

    MedlinePlus

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

  11. Projecting future drug expenditures--1997.

    PubMed

    Mehl, B; Santell, J P

    1997-01-15

    Use of the producer price index; data from independent sources, drug industry analyst, group purchasing organizations (GPOs), and health maintenance organizations (HMOs); pharmacoeconomics; and legal developments to project drug expenditures and prepare pharmacy budgets for 1997 is discussed. The producer price index indicates that prices for drugs and pharmaceuticals increased 2.2% during January to May 1996; the increase for prescription preparations was 3.4%. Medi-Span reports an average increase for all drug products of 1.2% for the first six months of 1996. IMS America data show the price of all drugs increasing 1.8% between the second quarters of 1995 and 1996. Drug industry analysts project the overall price increase in the next 12 months at 2.5-5.0%. GPOs predict an average increase over the next 12 months of 2.2% for contracted drugs and 4.3% for non-contracted drugs. HMO pharmacy directors predict pharmacy expenditures will increase by 4.5% per member in 1997. Caution must be applied in using pharmacoeconomics to project drug costs and their impact on health care expenditures. Today's budget must account for the greater integration of drug expenditures into the institution's objectives, possible reductions in other service costs, capitation, competition, shifting of control of the drug budget to specific patient care centers, relocation of services to the ambulatory care setting, and outsourcing. Legal actions in 1996 that may affect price increases and drug budgets included a class-action lawsuit by community and chain pharmacies alleging price discrimination by manufactures and wholesalers. Prices of pharmaceutical products are fairly stable and may remain so in 1997, but projections of future drug expenditures must account for the continuing reshaping of the health care landscape. PMID:9117803

  12. Drug delivery and nanoparticles: Applications and hazards

    PubMed Central

    De Jong, Wim H; Borm, Paul JA

    2008-01-01

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

  13. Religiosity and Drug Use among Inmates in Boot Camp: Testing a Theoretical Model with Reciprocal Relationships.

    ERIC Educational Resources Information Center

    Benda, Brent B.; Toombs, Nancy J.

    2002-01-01

    Examines the effects of religiosity within a theoretical model with reciprocal relationships of drug use among boot camp inmates. Findings show that attachment to caregivers is inversely related to associations with peers who engage in illicit behavior, whereas being abused by an adult is positively related to these associations. These…

  14. Sustained Drug Release on Temperature-Responsive Poly(N-isopropylacrylamide)-Integrated Hydroxyapatite

    SciTech Connect

    Shin, Yongsoon ); Liu, Jun; Chang, Jeong H.; Exarhos, Gregory J.)

    2002-01-01

    A hybrid temperature-responsive hydroxyapatite-poly(N-isopropylacrylamide) (HAP-PNIPAAm) gel has been synthesized by the interpenetration of PNIPAAm into a sintered HAP disk through a radical-initiated polymerization of NIPAAm monomers under N2 atmosphere, and shows sustained positive thermo-responsive drug release profile over a month at PBS buffer.

  15. A Drug-Centric View of Drug Development: How Drugs Spread from Disease to Disease

    PubMed Central

    Rodriguez-Esteban, Raul

    2016-01-01

    Drugs are often seen as ancillary to the purpose of fighting diseases. Here an alternative view is proposed in which they occupy a spearheading role. In this view, drugs are technologies with an inherent therapeutic potential. Once created, they can spread from disease to disease independently of the drug creator’s original intentions. Through the analysis of extensive literature and clinical trial records, it can be observed that successful drugs follow a life cycle in which they are studied at an increasing rate, and for the treatment of an increasing number of diseases, leading to clinical advancement. Such initial growth, following a power law on average, has a degree of momentum, but eventually decelerates, leading to stagnation and decay. A network model can describe the propagation of drugs from disease to disease in which diseases communicate with each other by receiving and sending drugs. Within this model, some diseases appear more prone to influence other diseases than be influenced, and vice versa. Diseases can also be organized into a drug-centric disease taxonomy based on the drugs that each adopts. This taxonomy reflects not only biological similarities across diseases, but also the level of differentiation of existing therapies. In sum, this study shows that drugs can become contagious technologies playing a driving role in the fight against disease. By better understanding such dynamics, pharmaceutical developers may be able to manage drug projects more effectively. PMID:27124390

  16. A Drug-Centric View of Drug Development: How Drugs Spread from Disease to Disease.

    PubMed

    Rodriguez-Esteban, Raul

    2016-04-01

    Drugs are often seen as ancillary to the purpose of fighting diseases. Here an alternative view is proposed in which they occupy a spearheading role. In this view, drugs are technologies with an inherent therapeutic potential. Once created, they can spread from disease to disease independently of the drug creator's original intentions. Through the analysis of extensive literature and clinical trial records, it can be observed that successful drugs follow a life cycle in which they are studied at an increasing rate, and for the treatment of an increasing number of diseases, leading to clinical advancement. Such initial growth, following a power law on average, has a degree of momentum, but eventually decelerates, leading to stagnation and decay. A network model can describe the propagation of drugs from disease to disease in which diseases communicate with each other by receiving and sending drugs. Within this model, some diseases appear more prone to influence other diseases than be influenced, and vice versa. Diseases can also be organized into a drug-centric disease taxonomy based on the drugs that each adopts. This taxonomy reflects not only biological similarities across diseases, but also the level of differentiation of existing therapies. In sum, this study shows that drugs can become contagious technologies playing a driving role in the fight against disease. By better understanding such dynamics, pharmaceutical developers may be able to manage drug projects more effectively. PMID:27124390

  17. Ultrasonic drug delivery in Oncology.

    PubMed

    Udroiu, Ion

    2015-01-01

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

  18. [The use of drugs to improve athletic performance].

    PubMed

    Kuipers, H; Hartgens, F

    1997-10-11

    In sports, medical drugs are applied for supposedly ergogenic effects. Forbidden drug use (doping) implies that the drug enhances performance, which is not always the case. Amphetamines are ergogenic particularly during short-term, explosive exercise. Amphetamines exert an ergolytic effect on high-intensity endurance exercise. Caffeine has an ergogenic effect on endurance performance in dosages of 3 to 6 mg/kg. Doping regulations allow a small amount of caffeine intake. Androgenic and anabolic steroids elicit an increase in muscle growth and strength. In females low doses appear to be ergogenic in all sport types. beta 2-adrenergic agonists appear to have a positive effect on strength and muscle growth. The effects on endurance performance are still unknown. Although growth hormone is used in sports, scientific studies show that compared with placebo no difference in strength and muscle volume is observed. Blood doping and administration of erythropoietin are effective in enhancing endurance performance. PMID:9550746

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

    ERIC Educational Resources Information Center

    James, William H.; Moore, David D.

    1997-01-01

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

  20. On a national drug policy for Bangladesh.

    PubMed

    Islam, N

    1984-01-01

    On April 27, 1982 the Ministry of Health of the government of Bangladesh, set up an 8-man expert committee to evaluate all the registered pharmaceutical products presently available, and to formulate a draft National Drug Policy. Objectives are: 1) to provide support for ensuring quality and availability of drugs; 2) to reduce drug prices; 3) to eliminate useless, nonessential, and harmful drugs from the market; 4) to promote local production of finished drugs; 5) to ensure coordination among government branches; 6) to develop a drug monitoring and information system; 7) to promote the scientific development and application of unani, ayurvedic, and homeopathic medicines; 8) to improve the standard of hospital and retail pharmacies; and 9) to insure good manufacturing practices. 16 criteria were agreed on as guidelines for evaluating the drugs on the country's market. Drugs in Bangladesh have been classified into 3 categories. The 1st is drugs that are positively harmful. They should be banned immediately and withdrawn from the market. There are 265 locally manufactured drugs and 40 imported drugs in this category. The 2nd, drugs to be slightly reformulated by eliminating some of their requirements. There are 134 drugs in this category. The 3rd is drugs that do not conform to 1 or more of the 16 criteria/guidelines. There are over 500 drugs in this category. The new drug policy will produce a saving of 800 million taka (US $32.4 million). Drug supply in Bangladesh is a problem. The public sector distributes 20% of the total. In the private sector, drugs are supplied through import and local production. Investment for research by the pharmaceutical companies is essential. The principles laid down by the International Federation of Pharmaceutical Manufacturers Associations for the supply of good medicine needs to be put into practice. PMID:6729960

  1. Antiplatelet Drugs

    PubMed Central

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

    2012-01-01

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

  2. Pattern of Drug Resistance and Risk Factors Associated with Development of Drug Resistant Mycobacterium tuberculosis in Pakistan

    PubMed Central

    Ullah, Irfan; Javaid, Arshad; Tahir, Zarfishan; Ullah, Obaid; Shah, Aamer Ali; Hasan, Fariha; Ayub, Najma

    2016-01-01

    Background Drug resistant tuberculosis (DR-TB) is a major public health problem in developing countries such as Pakistan. Objective The current study was conducted to assess the frequency of drug resistant tuberculosis including multi drug resistance (MDR- TB) as well as risk factors for development of DR-TB, in Punjab, Pakistan. Methodology Drug susceptibility testing (DST) was performed, using proportion method, for 2367 culture positive Mycobacterium tuberculosis (MTB) cases that were enrolled from January 2012 to December 2013 in the province of Punjab, Pakistan, against first-line anti-tuberculosis drugs. The data was analyzed using statistical software; SPSS version 18. Results Out of 2367 isolates, 273 (11.5%) were resistant to at least one anti-TB drug, while 221 (9.3%) showed MDR- TB. Risk factors for development of MDR-TB were early age (ranges between 10–25 years) and previously treated TB patients. Conclusion DR-TB is a considerable problem in Pakistan. Major risk factors are previous history of TB treatment and younger age group. It emphasizes the need for effective TB control Program in the country. PMID:26809127

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    PubMed

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

    2003-10-01

    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

  5. Human egocentric position estimation.

    PubMed

    Yazdanbakhsh, Arash; Gagliardi, Celia

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPP improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.

  7. 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.

  8. 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.

  9. 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.

  10. Urine drug screen

    MedlinePlus

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

  11. Medication/Drug Allergy

    MedlinePlus

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

  12. Drug Plan Coverage Rules

    MedlinePlus

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

  13. Recovery position - series (image)

    MedlinePlus

    ... CPR, the victim should be placed in the recovery position. The recovery position helps keep the victim's airway open. To put the victim in the recovery position grab the victim's leg and shoulder and ...

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

    PubMed

    Davey, J; Leal, N; Freeman, J

    2007-05-01

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

  15. Positive Classroom Environments = Positive Academic Results

    ERIC Educational Resources Information Center

    Wilson-Fleming, LaTerra; Wilson-Younger, Dylinda

    2012-01-01

    This article discusses the effects of a positive classroom environment and its impact on student behavior and achievement. It also provides strategies for developing expectations for student achievement and the importance of parental involvement. A positive classroom environment is essential in keeping behavior problems to a minimum. There are a…

  16. Positive Education: Positive Psychology and Classroom Interventions

    ERIC Educational Resources Information Center

    Seligman, Martin E. P.; Ernst, Randal M.; Gillham, Jane; Reivich, Karen; Linkins, Mark

    2009-01-01

    Positive education is defined as education for both traditional skills and for happiness. The high prevalence worldwide of depression among young people, the small rise in life satisfaction, and the synergy between learning and positive emotion all argue that the skills for happiness should be taught in school. There is substantial evidence from…

  17. Want Positive Behavior? Use Positive Language

    ERIC Educational Resources Information Center

    Wood, Chip; Freeman-Loftis, Babs

    2012-01-01

    Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

  18. Drugs and the Brain.

    ERIC Educational Resources Information Center

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

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

  19. Drugs and Alcohol: Their Relative Crash Risk

    PubMed Central

    Romano, Eduardo; Torres-Saavedra, Pedro; Voas, Robert B.; Lacey, John H.

    2014-01-01

    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

  20. In vitro drug release mechanism and drug loading studies of cubic phase gels.

    PubMed

    Lara, Marilisa G; Bentley, M Vitória L B; Collett, John H

    2005-04-11

    Glyceryl monooleate/water cubic phase systems were investigated as drug delivery systems, using salicylic acid as a model drug. The liquid crystalline phases formed by the glyceryl monooleate (GMO)/water systems were characterized by polarizing microscopy. In vitro drug release studies were performed and the influences of initial water content, swelling and drug loading on the drug release properties were evaluated. Water uptake followed second-order swelling kinetics. In vitro release profiles showed Fickian diffusion control and were independent on the initial water content and drug loading, suggesting GMO cubic phase gels suitability for use as drug delivery system. PMID:15778062