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1

Melanoma Drug Trials Show Significant Promise  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Melanoma Drug Trials Show Significant Promise By targeting immune ... Monday, June 2, 2014 Related MedlinePlus Pages Medicines Melanoma MONDAY, June 2, 2014 (HealthDay News) -- A relatively ...

2

New Psoriasis Drug Shows Promise in Trials  

MedlinePLUS

... features on this page, please enable JavaScript. New Psoriasis Drug Shows Promise in Trials Secukinumab appears more ... Wednesday, July 9, 2014 Related MedlinePlus Pages Medicines Psoriasis WEDNESDAY, July 9, 2014 (HealthDay News) -- A new ...

3

New Eczema Drug Shows Promise in Early Trials  

MedlinePLUS

... sharing features on this page, please enable JavaScript. New Eczema Drug Shows Promise in Early Trials Dupilumab ... Eczema THURSDAY, July 10, 2014 (HealthDay News) -- A new drug that scientists hope will relieve the debilitating ...

4

Drug-induced liver injury following positive drug rechallenge  

Microsoft Academic Search

Drug rechallenge (or reinitiation), following an event of drug-induced liver injury, can lead to serious or fatal liver injury. A retrospective review of a large pharmaceutical safety database was conducted to assess clinical outcomes of positive drug rechallenge following possible drug-induced liver injury.Positive rechallenge with suspect drug was reported in 770 of 36,795 hepatic adverse events. A total of 88

Julie I. Papay; Dawn Clines; Rezvan Rafi; Nancy Yuen; Susan D. Britt; John S. Walsh; Christine M. Hunt

2009-01-01

5

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

6

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

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

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

7

FEATURE 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

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

10

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

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

New Drug Shows Promise for Restless Legs Syndrome  

MedlinePLUS

... sharing features on this page, please enable JavaScript. New Drug Shows Promise for Restless Legs Syndrome: Study ... medication in a head-to-head comparison, a new study found. Pramipexole (Mirapex), which is commonly used ...

13

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

PubMed

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

Gramel, Sabine

2005-01-01

14

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

15

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

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

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

16

MEK: A Single Drug Target Shows Promise in Multiple Cancers  

Cancer.gov

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

17

Targeted Drug for Melanoma Shows Promise in Early Clinical Testing  

Cancer.gov

The vast majority of patients with advanced melanoma who received an experimental targeted drug called PLX4032 responded to the treatment in a phase I clinical trial, researchers reported in the August 26, 2010, New England Journal of Medicine.

18

Multisite study shows drug offers relief for symptoms of myelofibrosis  

Cancer.gov

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

19

Stomach Cancer Drug, S-1, Shows Promise in Japanese Trial  

Cancer.gov

In this Japanese clinical trial, patients with advanced, inoperable stomach cancer who received combination therapy with cisplatin and a drug called S-1 lived about two months longer than patients treated with S-1 alone, according to the March 2008 Lancet Oncology.

20

Family Checkup: Positive Parenting Prevents Drug Abuse  

MedlinePLUS

... Treatment Locator or 1-800-662-HELP . Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ... Teen About Drug Use? Share This Badge NIDA Publications for Parents Preventing Drug Use among Children and ...

21

New cancer drug shows promise for treating advanced melanoma  

Cancer.gov

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

22

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

MedlinePLUS

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

23

First Phase 0 Oncology Trial Shows Effectiveness of New Drug on Its Target  

Cancer.gov

The first phase 0 clinical trial of a drug in cancer treatment, involving 13 patients with advanced cancers, showed that the drug, ABT-888, affected its target and was well tolerated. Most importantly, this trial showed that it is possible to enroll a small number of patients, treat them with a low dose of a new drug, identify whether the desired target of the drug was affected, and obtain all of this critical information relatively quickly.

24

Hybrid Nanogels for Sustainable Positive Thermosensitive Drug Release  

SciTech Connect

A hybrid nanogel is developed based on interpenetrating networks of thermosensitive PNIPAAm gels and tailored nanoporous silica. Sustainable positive thermo-responsive drug release profile is obtained. When the temperature rises, the polymer gel shrinks, squeezing the drug into the porous channels, and at the same time, opening the pore to the outside media. The drug slowly diffuses out of the porous channels. The overall release rate can be adjusted by changing the composition of the nanogel.

Shin, Yongsoon (BATTELLE (PACIFIC NW LAB)); Chang, Jeong H. (ASSOC WESTERN UNIVERSITY); Liu, Jun (Lucent Bell Laboratories); Williford, Rick E. (BATTELLE (PACIFIC NW LAB)); Shin, Young-Kook (Chungbuk National University); Exarhos, Gregory J. (BATTELLE (PACIFIC NW LAB))

2001-05-18

25

Hybrid nanogels for sustainable positive thermosensitive drug release  

Microsoft Academic Search

A hybrid nanogel has been developed based on interpenetrating networks of thermosensitive poly(N-isopropylacrylamide) gels and tailored nanoporous silica. A sustainable positive thermo-responsive drug release profile is obtained. When the temperature rises, the polymer gel shrinks, squeezing the drug into the porous channels, and at the same time, opening the pores to the outside media. The drug slowly diffuses out of

Yongsoon Shin; Jeong Ho Chang; Jun Liu; Rick E. Williford; Young-Kook Shin; Gregory J. Exarhos

2001-01-01

26

Report Shows Combining Drug Use with Underage Drinking Raises Health Risks  

MedlinePLUS

... shows combining drug use with underage drinking raises health risks Underage drinkers (ages 12 to 20) who were ... million underage drinkers across America are putting their health and futures at risk – even more so when they combine alcohol with ...

27

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

Cancer.gov

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

28

Dimethylamylamine: a drug causing positive immunoassay results for amphetamines.  

PubMed

The Department of Defense (DoD) operates six forensic urine drug-testing laboratories that screen close to 5 million urine samples for amphetamines yearly. Recently, the DoD laboratories have observed a significant decrease in the confirmation rates for amphetamines because of specimens screening positive by two separate immunoassays and confirming negative by gas chromatography-mass spectrometry (GC-MS). Previous studies conducted by the Division of Forensic Toxicology, Armed Force Institute of Pathology (AFIP) utilizing a GC-MS basic drug screen and a designer drug screen revealed no common compound or compound classes as to the cause of the immunoassay-positive results. Additional information obtained from an immunoassay vendor suggested the anorectic compound dimethylamylamine (DMAA) may be the cause of the false-positive screens. An additional 134 false-positive samples were received and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for DMAA. LC-MS-MS analysis revealed the presence of DMAA in 92.3% of the false-positive samples at a concentration of approximately 6.0 mg/L DMAA, causing a positive screen on both immunoassay kits. PMID:21439156

Vorce, Shawn P; Holler, Justin M; Cawrse, Brian M; Magluilo, Joseph

2011-04-01

29

International phase I clinical trial shows drug shrinks melanoma brain metastases  

Cancer.gov

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

30

The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis  

PubMed Central

Safer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50-60,000 people each year. Here we report that fexinidazole, a drug currently in phase I clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg kg?1) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC99 value for at least 24h following a single oral dose. A once daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of visceral leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat visceral leishmaniasis. In African trypanosomes, the mode of action of nitro-drugs involves reductive activation via an NADH-dependent bacterial-like nitroreductase. Overexpression of the leishmanial homologue of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating visceral leishmaniasis.

Wyllie, Susan; Patterson, Stephen; Stojanovski, Laste; Simeons, Frederick R. C.; Norval, Suzanne; Kime, Robert; Read, Kevin D.; Fairlamb, Alan H.

2012-01-01

31

Factors Associated with Serum HCV RNA Positivity in Anti-HCV Antibody Positive Intravenous Drug Users  

Microsoft Academic Search

Serum hepatitis C virus (HCV) RNA, HCV genotypes and liver function tests were evaluated in a series of 189 unselected, consecutive anti-HCV positive intravenous drug users (IVDUs). Serum HCV RNA was detected in 106\\/189 patients. Abnormal liver function tests were associated with alcohol abuse, but not with the presence of serum HCV RNA. Among 109 patients retested after a mean

Mario Pirisi; Pierluigi Toniutto; Carlo Fabris; Tiziana Lombardelli; Edmondo Falleti; Sergio G Tisminetzky; Francisco Baralle; Ettore Bartoli

1998-01-01

32

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

Cancer.gov

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

33

Influence of anatomy and head position on intranasal drug deposition.  

PubMed

The objective of this study was to determine the influence of individual anatomical differences on intranasal drug deposition. The data of a comparison of seven different administration techniques in ten healthy volunteers was used in this single-blind crossover pilot study. After intranasal administration of a dyed test formulation, endoscopic video imaging was done on seven non-sequential days. The deposition pattern per individual around the head of the middle turbinate was analyzed for each technique and correlated with the individual anatomy. Decreased deposition of dyed test formulation in the target area around the head of the middle turbinate was observed in the presence of minor septal deviations, narrow nasal valve areas, or inferior turbinate hypertrophy; a lateral head position helps to bypass a minor septal deviation. Although results are preliminary, we conclude that anatomy and head position are important factors in the deposition of topical nasal drugs and may be the key to improving individual local nasal (steroid) treatment. PMID:16807754

Merkus, Paul; Ebbens, Fenna A; Muller, Barbara; Fokkens, Wytske J

2006-09-01

34

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

PubMed

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

Moriya, Fumio

2009-04-01

35

Legal Position of School Personnel -- Drugs and Narcotics.  

ERIC Educational Resources Information Center

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

Shannon, Thomas A.

36

Aldehyde dehydrogenase 1 positive glioblastoma cells show brain tumor stem cell capacity  

PubMed Central

Glioblastoma (GBM) is the most aggressive primary brain tumor and is resistant to all therapeutic regimens. Relapse occurs regularly and might be caused by a poorly characterized tumor stem cell (TSC) subpopulation escaping therapy. We suggest aldehyde dehydrogenase 1 (ALDH1) as a novel stem cell marker in human GBM. Using the neurosphere formation assay as a functional method to identify brain TSCs, we show that high protein levels of ALDH1 facilitate neurosphere formation in established GBM cell lines. Even single ALDH1 positive cells give rise to colonies and neurospheres. Consequently, the inhibition of ALDH1 in vitro decreases both the number of neurospheres and their size. Cell lines without expression of ALDH1 do not form tumor spheroids under the same culturing conditions. High levels of ALDH1 seem to keep tumor cells in an undifferentiated, stem cell-like state indicated by the low expression of beta-III-tubulin. In contrast, ALDH1 inhibition induces premature cellular differentiation and reduces clonogenic capacity. Primary cell cultures obtained from fresh tumor samples approve the established GBM cell line results.

Rasper, Michael; Schafer, Andrea; Piontek, Guido; Teufel, Julian; Brockhoff, Gero; Ringel, Florian; Heindl, Stefan; Zimmer, Claus; Schlegel, Jurgen

2010-01-01

37

Aldehyde dehydrogenase 1 positive glioblastoma cells show brain tumor stem cell capacity.  

PubMed

Glioblastoma (GBM) is the most aggressive primary brain tumor and is resistant to all therapeutic regimens. Relapse occurs regularly and might be caused by a poorly characterized tumor stem cell (TSC) subpopulation escaping therapy. We suggest aldehyde dehydrogenase 1 (ALDH1) as a novel stem cell marker in human GBM. Using the neurosphere formation assay as a functional method to identify brain TSCs, we show that high protein levels of ALDH1 facilitate neurosphere formation in established GBM cell lines. Even single ALDH1 positive cells give rise to colonies and neurospheres. Consequently, the inhibition of ALDH1 in vitro decreases both the number of neurospheres and their size. Cell lines without expression of ALDH1 do not form tumor spheroids under the same culturing conditions. High levels of ALDH1 seem to keep tumor cells in an undifferentiated, stem cell-like state indicated by the low expression of beta-III-tubulin. In contrast, ALDH1 inhibition induces premature cellular differentiation and reduces clonogenic capacity. Primary cell cultures obtained from fresh tumor samples approve the established GBM cell line results. PMID:20627895

Rasper, Michael; Schäfer, Andrea; Piontek, Guido; Teufel, Julian; Brockhoff, Gero; Ringel, Florian; Heindl, Stefan; Zimmer, Claus; Schlegel, Jürgen

2010-10-01

38

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

PubMed

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

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

2008-01-01

39

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

PubMed Central

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

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

2008-01-01

40

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

NSDL National Science Digital Library

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

APS Communications Office (American Physiological Society Communications Office)

2006-04-17

41

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

Microsoft Academic Search

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

Steven Grant; Carlo Contoreggi; Edythe D. London

2000-01-01

42

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

ERIC Educational Resources Information Center

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)

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

1997-01-01

43

Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs  

PubMed Central

It is the mature gametocytes of Plasmodium that are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases. Gametocytes, however, are not a homogeneous cell population. They are sexually dimorphic, and both males and females are required for parasite transmission. Using two bioassays, we explored the effects of 20 antimalarials on the functional viability of both male and female mature gametocytes of Plasmodium falciparum. We show that mature male gametocytes (as reported by their ability to produce male gametes, i.e., to exflagellate) are sensitive to antifolates, some endoperoxides, methylene blue, and thiostrepton, with submicromolar 50% inhibitory concentrations (IC50s), whereas female gametocytes (as reported by their ability to activate and form gametes expressing the marker Pfs25) are much less sensitive to antimalarial intervention, with only methylene blue and thiostrepton showing any significant activity. These findings show firstly that the antimalarial responses of male and female gametocytes differ and secondly that the mature male gametocyte should be considered a more vulnerable target than the female gametocyte for transmission-blocking drugs. Given the female-biased sex ratio of Plasmodium falciparum (?3 to 5 females:1 male), current gametocyte assays without a sex-specific readout are unlikely to identify male-targeted compounds and prioritize them for further development. Both assays reported here are being scaled up to at least medium throughput and will permit identification of key transmission-blocking molecules that have been overlooked by other screening campaigns.

Ruecker, Andrea; Straschil, Ursula; Lelievre, Joel; Marques, Sara; Lopez-Barragan, Maria Jose; Herreros, Esperanza; Sinden, Robert E.

2013-01-01

44

Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs.  

PubMed

It is the mature gametocytes of Plasmodium that are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases. Gametocytes, however, are not a homogeneous cell population. They are sexually dimorphic, and both males and females are required for parasite transmission. Using two bioassays, we explored the effects of 20 antimalarials on the functional viability of both male and female mature gametocytes of Plasmodium falciparum. We show that mature male gametocytes (as reported by their ability to produce male gametes, i.e., to exflagellate) are sensitive to antifolates, some endoperoxides, methylene blue, and thiostrepton, with submicromolar 50% inhibitory concentrations (IC50s), whereas female gametocytes (as reported by their ability to activate and form gametes expressing the marker Pfs25) are much less sensitive to antimalarial intervention, with only methylene blue and thiostrepton showing any significant activity. These findings show firstly that the antimalarial responses of male and female gametocytes differ and secondly that the mature male gametocyte should be considered a more vulnerable target than the female gametocyte for transmission-blocking drugs. Given the female-biased sex ratio of Plasmodium falciparum (?3 to 5 females:1 male), current gametocyte assays without a sex-specific readout are unlikely to identify male-targeted compounds and prioritize them for further development. Both assays reported here are being scaled up to at least medium throughput and will permit identification of key transmission-blocking molecules that have been overlooked by other screening campaigns. PMID:23629698

Delves, Michael J; Ruecker, Andrea; Straschil, Ursula; Lelièvre, Jöel; Marques, Sara; López-Barragán, María José; Herreros, Esperanza; Sinden, Robert E

2013-07-01

45

DO REWARDLESS ORCHIDS SHOW A POSITIVE RELATIONSHIP BETWEEN PHENOTYPIC DIVERSITY AND REPRODUCTIVE SUCCESS?  

Microsoft Academic Search

Among rewardless orchids, pollinator sampling behavior has been suggested to drive a positive relationship between population phenotypic variability and absolute reproductive success, and hence population fitness. We tested this hypothesis by constructing experimental arrays using the rewardless orchid Dactylorhiza sambucina, which is dimorphic for corolla color. We found no evidence that polymorphic arrays had higher mean reproductive success than monomorphic

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

2007-01-01

46

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

Cancer.gov

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

47

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

Cancer.gov

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

48

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

Cancer.gov

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

49

Suture Granuloma Showing False-Positive Findings on FDG-PET.  

PubMed

We report a case of a 33-year-old male with a mixed germ-cell testicular tumor. Postoperative follow-up FDG-PET revealed concentration of FDG in the left inguinal area which is not tumor metastasis or local recurrence but suture reactivity granuloma. In this paper, we reviewed suture granulomas associated with false-positive findings on FDG-PET after surgery. If FDG-PET will be used more frequently in the future, it will be necessary to refrain from using silk thread in order to prevent any unnecessary surgery. PMID:23762743

Takahara, Kohei; Kakinoki, Hiroaki; Ikoma, Saya; Udo, Kazuma; Tobu, Shohei; Satoh, Yuji; Tokuda, Yuji; Noguchi, Mitsuru; Aoki, Shigehisa; Uozumi, Jiro

2013-01-01

50

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

PubMed

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

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

2007-02-01

51

The positive correlation between DJ-1 and ?-catenin expression shows prognostic value for patients with glioma.  

PubMed

The relationship between DJ-1 and ?-catenin, and its impact on the prognosis for glioma patients has not been fully understood. This study determined the effect of DJ-1 on ?-catenin and the prognostic significance of this interaction in glioma patients. We collected tumor specimens from 88 glioma patients and determined the expression of DJ-1, ?-catenin and PTEN by using immunohistochemical staining. The involvement of DJ-1 and ?-catenin in glioma cell lines was evaluated by immunohistochemistry and Western blotting. High DJ-1 expression (37.5%) and high ?-catenin expression (34.1%) in glioma specimens were significantly associated with high grade and poor prognosis in glioma patients. However, only high levels of DJ-1 (P = 0.014) was a strong independent prognostic factor, correlated with a reduced overall survival time. In vitro?DJ-1 expression was positively correlated with the expression levels of ?-catenin and p-Akt, and negatively correlated with PTEN expression in U87, U251 MG, SWO-38 and SHG44 human glioma cell lines. After the knockdown of DJ-1, Akt, p-Akt or ?-catenin expression levels were not affected in the PTEN-null cell lines (U87 and U251 MG). However, in the SWO-38 cell line, which has wild-type PTEN protein, the level of PTEN increased while Akt/p-Akt and ?-catenin levels were reduced. Furthermore, ?-catenin staining weakened in SWO-38 cells after DJ-1 levels decreased according to immunocytochemical analysis. In conclusion, DJ-1 and ?-catenin may contribute to the development and recurrence of glioma and are valuable prognostic factors for glioma patients. DJ-1 may regulate ?-catenin expression via PTEN and p-Akt. PMID:23714193

Wang, Chao; Fang, Mao; Zhang, Meng; Li, Weiping; Guan, Hong; Sun, Yanhua; Xie, Siming; Zhong, Xueyun

2013-12-01

52

Sexual Risk Taking among HIV-Positive Injection Drug Users: Contexts, Characteristics, and Implications for Prevention  

ERIC Educational Resources Information Center

HIV-positive injection drug users (IDUs) (N = 161) were recruited to complete a qualitative interview and a quantitative survey about sexual behavior and transmission risk. We identified two contexts in which exposure encounters occurred most commonly for HIV-positive IDUs: in intimate serodiscordant relationships and in the drug/sex economy.…

Knight, Kelly R.; Purcell, David; Dawson-Rose, Carol; Halkitis, Perry N.; Gomez, Cynthia A.

2005-01-01

53

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

Microsoft Academic Search

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

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

2011-01-01

54

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

Microsoft Academic Search

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

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

2012-01-01

55

Studies show new drug to be effective in treating skin cancer  

Cancer.gov

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

56

HIV drug shows efficacy in treating mouse models of HER2+ breast cancer  

Cancer.gov

The HIV protease inhibitor, Nelfinavir, can be used to treat HER2-positive breast cancer in the same capacity and dosage regimen that it is used to treat HIV, according to a Johns Hopkins School of Medicine study published October 5 in the Journal of the National Cancer Institute. Johns Hopkins University is home to the Sidney Kimmel Comprehensive Cancer Center.

57

Olig2-positive cells in glioneuronal tumors show both glial and neuronal characters: the implication of a common progenitor cell?  

PubMed

Glioneuronal tumors (GNTs) are rare neoplasms consisting of both glial and neuronal components. Among the GNTs, dysembryoplastic neuroepithelial tumors (DNTs), papillary glioneuronal tumors (PGNTs), and rosette-forming glioneuronal tumors of the fourth ventricle (RGNTs) share the character of being mainly composed of small round Olig2-positive tumor cells. Using immunohistochemistry and fluorescence in situ hybridization, we examined a series of 35 GNT cases (11 DNTs, 15 PGNTs and 9 RGNTs) on the characteristics of Olig2-positive tumor cells. Histologically, Olig2-positive cells showed small round forms in most GNTs; however, there were a small number of Olig2-positive cells with neuronal morphology only in a PGNT case. These cells expressed both glial and neuronal markers by double immunostaining. With regard to labeling indices and intensity, only PGNT cells expressed neuronal markers, including ?-internexin and neurofilament. These findings also suggest that some Olig2-positive PGNT cells may show neuronal differentiation. In GNTs, a considerable number of Olig2-positive cells showed immunopositivity for cyclin D1 and/or platelet-derived growth factor receptor alpha (PDGFR?), which are markers for oligodendrocyte progenitor cells. These immunostainings were particularly strong in DNTs. In RGNTs, Olig2-positive cells formed "neurocytic rosettes". Furthermore, they were also immunopositive for glial markers, including GFAP, PDGFR? and cyclin D1. These findings indicate the heterogeneous characteristics of Olig2-positive cells in GNTs, and some of them also exhibited neuronal features. So it is possible that a part of Olig2-positive GNT cells have characteristics similar to those of progenitor cells. PMID:23025580

Matsumura, Nozomi; Yokoo, Hideaki; Mao, Ying; Yin, Wang; Nakazato, Yoichi

2013-06-01

58

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

PubMed Central

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.

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

1995-01-01

59

Caught between freedom and control: ‘ordinary’ people’s discursive positioning on an Israeli prime-time talk show  

Microsoft Academic Search

The article discusses the democratizing potential of the talk show genre by exploring the discursive positioning of anonymous lay participants in the Israeli prime-time talk show Live. Quantitative analyses of three measures of participation reveal that anonymous guests take fewer turns, intervene less and self-select less than famous and semi-famous guests on the show. Qualitative analyses reveal a dialectical response

Michal Hamo

2006-01-01

60

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

PubMed Central

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

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

2004-01-01

61

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

PubMed

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

Mishra, Jyotsna; Madhubala, Rentala; Singh, Sarman

2013-03-01

62

Finding meaning: African American injection drug users’ interpretations of testing HIV-positive  

Microsoft Academic Search

In the US, African American injection drug users have increased risk for acquiring HIV and for not having long-term survival post AIDS diagnosis. This study examines the cognitive interpretations African American injection drug users make of an HIV-positive test result and the attitudinal and behavioural patterns that accompany those interpretations. Using snowball sampling techniques, street outreach was used to recruit

M. Valle; J. Levy

2008-01-01

63

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

Cancer.gov

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

64

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

PubMed

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

De Leon, G

1994-01-01

65

Sensitization to petrolatum: an unusual cause of false-positive drug patch-tests.  

PubMed

We report on an unexpected sensitization to petrolatum diagnosed with the occurrence of multiple nonrelevant and false-positive drug patch-tests performed while investigating a patient suffering from many cutaneous adverse drug reactions. All the positive drug patch-tests were prepared with GILBERT vaseline. This petrolatum reaction is positive as it was tested with five other brands of petrolatums a few months later. As the same petrolatums, but from different batches were tested, patch-tests with GILBERT petrolatum were doubtful, while other petrolatums were positive. White petrolatum is a mixture of semisolid hydrocarbons of the methane series. The sensitizing impurities of petrolatum are polycyclic aromatic hydrocarbons, e.g. phenanthrene derivatives. The purity of petrolatum depends on both the petroleum stock and on the production and packaging methods. Even if rare, contact sensitization to petrolatum can disturb the interpretation of drug patch-tests. It is necessary in the interpretation of drug patch-tests to test both in petrolatum and other vehicles and with all the different petrolatums used in preparing the material for drug patch-tests. So, it is essential to advise the patients sensitized to petrolatum to remove all the topical drugs, such as all the cosmetics, which contain petrolatum in their formulation. PMID:15291911

Ulrich, G; Schmutz, J L; Trechot, Ph; Commun, N; Barbaud, A

2004-09-01

66

[Lidamycin inhibits the proliferation of HERG K+ channel highly expressing cancer cells and shows synergy with anticancer drugs].  

PubMed

This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs. PMID:22260022

Shang, Bo-yang; Shang, Yue; Zhen, Yong-su; Chen, Shu-zhen

2011-11-01

67

Drug testing in the workplace: could a positive test for one of the mandated drugs be for reasons other than illicit use of the drug?  

PubMed

This manuscript reviews data available in the scientific literature relative to drug testing for the five mandated drug classes and circumstances other than abuse of the drug itself that could result in a positive test. For marijuana, passive inhalation, unknowing oral ingestion, and the use of Marinol are discussed. Data are presented on the concentration of delta9-tetrahydrocannabinol (THC) and its precursors, acid-A and acid-B, in illicit marijuana and the extent of extraction of THC in boiled (tea) or cooked products. For cocaine, passive inhalation and passive exposure issues are reviewed. For opiates, poppy seed ingestion and guidelines for exclusion of poppy seeds as a cause for a positive test are discussed. For amphetamines, issues such as the presence of other phenethylamines, l-methamphetamine (Vicks' inhalers), and other prescription drugs are discussed. Although passive inhalation of methamphetamine and phencyclidine is theoretically possible, no data were available on these issues. PMID:8926740

elSohly, M A; Jones, A B

1995-10-01

68

Adult Drug Courts: Studies Show Courts Reduce Recidivism, but DOJ Could Enhance Future Performance Measure Revision Efforts.  

National Technical Information Service (NTIS)

A drug court is a specialized court that targets criminal offenders who have drug addiction and dependency problems. These programs provide offenders with intensive court supervision, mandatory drug testing, substance-abuse treatment, and other social ser...

2011-01-01

69

Protamine 3 shows evidence of weak, positive selection in mouse species (genus Mus)--but it is not a protamine.  

PubMed

Protamines are short and highly basic sperm-specific nuclear proteins that replace somatic histones during spermiogenesis in a process that is crucial for sperm formation and function. Many mammals have two protamine genes (PRM1 and PRM2) located in a gene cluster, which appears to evolve fast. Another gene in this cluster (designated protamine 3 [PRM3]) encodes a protein that is conserved among mammals but that does not seem to be involved in chromatin condensation. We have compared protein sequences and amino acid compositions of protamines in this gene cluster, searched for evidence of positive selection of PRM3, and examined whether sexual selection (sperm competition) may drive the evolution of the PRM3 gene. Nucleotide and amino acid analyses of mouse sequences revealed that PRM3 was very different from PRM1 and from both the precursor and the mature sequences of PRM2. Among 10 mouse species, PRM3 showed weak evidence of positive selection in two species, but there was no clear association with levels of sperm competition. In analyses from among mammalian species, no evidence of positive selection was found in PRM3. We conclude that PRM3 exhibits several clear differences from other protamines and, furthermore, that it cannot be regarded as a true protamine. PMID:20944085

Martin-Coello, Juan; Gomendio, Montserrat; Roldan, Eduardo R S

2011-02-01

70

Neurocognitive Aspects of Medication Adherence in HIV-Positive Injecting Drug Users  

Microsoft Academic Search

Cognitive deficits are associated with nonadherence to HIV medications. HIV-positive injecting drug users (IDUs) are at particular risk for nonadherence and cognitive barriers to adherence specific to this population should therefore be identified. The present study assessed the relation of three domains of cognitive functioning, executive functions, memory, and psychomotor speed, to self-reported antiretroviral adherence in a sample of HIV-positive

Drenna Waldrop-Valverde; Raymond L. Ownby; Frances L. Wilkie; Alison Mack; Mahendra Kumar; Lisa Metsch

2006-01-01

71

Finding meaning: African American injection drug users' interpretations of testing HIV-positive.  

PubMed

In the US, African American injection drug users have increased risk for acquiring HIV and for not having long-term survival post AIDS diagnosis. This study examines the cognitive interpretations African American injection drug users make of an HIV-positive test result and the attitudinal and behavioural patterns that accompany those interpretations. Using snowball sampling techniques, street outreach was used to recruit 839 African American injection drug users and their partners for HIV testing and counselling. Subsequently, data were collected for 80 individuals who tested HIV-positive. Individuals who interpreted testing HIV-positive as a 'wake up call' displayed the attitudinal and behavioural patterns of 'being blessed', 'living clean' and 'advocacy'. Those that interpreted the test result as a 'death knell' displayed 'self-destructive', 'pleasure-seeking' and 'vengeance'. Those that interpreted the positive test result as 'just one more problem' displayed 'resignation' and 'minimization'. The period following the diagnosis of HIV provides an opportunity for intervention. A positive HIV status can produce lifestyle changes that either facilitate or militate against a person's health and quality of life. HIV-prevention efforts can be improved by helping individuals living with the virus to interpret and act on their diagnosis in positive ways. PMID:18278624

Valle, M; Levy, J

2008-01-01

72

Positively charged polyethylenimines enhance nasal absorption of the negatively charged drug, low molecular weight heparin  

Microsoft Academic Search

This study tests the hypothesis that positively charged polyethylenimines (PEIs) enhance nasal absorption of low molecular weight heparin (LMWH) by reducing the negative surface charge of the drug molecule. Physical interactions between PEIs and LMWH were studied by Fourier transform infrared (FTIR) spectroscopy, particle size analysis, conductivity measurements, zeta potential analysis, and azure A assay. The efficacy of PEIs in

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

2006-01-01

73

Sexual Transmission Risk Behavior Reported Among Behaviorally Bisexual HIV-Positive Injection Drug-Using Men  

Microsoft Academic Search

Background: Few research studies have examined the HIV trans- mission risk behaviors of HIV-positive injection drug users (IDUs) who are men who have sex with men and women (MSMW). Methods: We compared unprotected vaginal or anal sex with an HIV-negative or unknown (UNK) status sexual partner of MSMW (n = 118) with men who have sex exclusively with women (MSW;

Kelly R. Knight; Starley B. Shade; David W. Purcell; Carol Dawson Rose; Lisa R. Metsch; Mary H. Latka; Carl A. Latkin; Cynthia A. Gomez

2007-01-01

74

A novel excipient, 1-perfluorohexyloctane shows limited utility for the oral delivery of poorly water-soluble drugs.  

PubMed

The applicability of the semi-fluorinated alkane 1-perfluorohexyloctane (F6H8) as a novel excipient in lipid based drug delivery systems was studied. Solubility studies of 11 poorly water soluble drugs (cinnarizine, danazol, estradiol, fenofibrate, griseofulvin, halofantrine, lidocaine, prednisolone, probucol, rolipram and siramesine) showed significantly lower equilibrium solubility in F6H8 compared to soy bean oil (long chain triglyceride). F6H8 was miscible with medium chain triglycerides (MCT) but not miscible with long chain triglycerides, neither was pure F6H8 nor the mixture F6H8:MCT (1:1) miscible with 7 commonly used surfactants (Cremophor EL, Span 20, Span 80, Labrasol, Softigen 767 and Gelucire 44/14, polysorbate 80). In vitro lipolysis studies confirmed that F6H8 was non-digestible. F6H8:MCT (1:1) showed initially faster lipolysis compared to pure MCT. Thus, final phase lipolysis was lower indicating that F6H8 may affect the lipolysis of MCT. However, in vivo bioavailability studies in rats showed the same plasma concentration-time profiles when dosing 10mg/kg halofantrine at two dose levels of F6H8, MCT or F6H8:MCT (1:1) (AUC ranged from 3058 to 3447hng/ml, T(max)?6.0h, C(max) ranged from 168 to 265mg/ml). Generally, the addition of polysorbate 80 shortened the time to reach C(max) (T(max) ranged 1.3-4.5h), but had limited effect on the bioavailability from F6H8 or MCT in combination with polysorbate 80 (4:1) (AUC ranged from 3807 to 4403 (hng/ml)). Although a synergistic effect was obtained with halofantrine in F6H8:MCT:polysorbate 80 (2:2:1) (AUC 5574±675hng/ml; mean±SEM), it was not superior to dosing halofantrine in pure polysorbarte 80 (AUC 7370±579hng/ml; mean±SEM). The applicability of F6H8 as an excipient for future use in lipid based formulations for poorly water soluble drugs is therefore considered to be very limited. PMID:21256961

Holm, René; Jørgensen, Erling Bonne; Harborg, Michael; Larsen, Rune; Holm, Per; Müllertz, Anette; Jacobsen, Jette

2011-03-18

75

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

PubMed Central

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.

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

2012-01-01

76

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

PubMed Central

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

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

2012-01-01

77

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

Code of Federal Regulations, 2013 CFR

...verified positive drug test result and/or breath alcohol test result of 0...TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS...verified positive drug test result and/or breath alcohol test result of...

2013-10-01

78

Yersinia enterocolitica serotype O:9 cultured from Swedish sheep showing serologically false-positive reactions for Brucella melitensis  

PubMed Central

In a herd of 20 sheep in Sweden, a country where brucellosis has never been diagnosed in sheep or goats, a total of six sheep were found serologically positive to Brucella melitensis in two different rounds of sampling. Yersinia enterocolitica serotype O:9 could at the time of the second sampling be isolated from four sheep, one of them at the same time serologically positive for B. melitensis. The article describes the case and gives some background information on brucellosis and Y. enterocolitica in general as well as a more specific description of the Swedish surveillance program for B. melitensis and the test procedures used. The problem with false-positive reactions, in particular its implications for surveillance programs in low prevalence or officially brucellosis-free countries, is discussed.

Chenais, Erika; Bagge, Elisabeth; Lambertz, Susanne Thisted; Artursson, Karin

2012-01-01

79

Effect of positively and negatively charged liposomes on skin permeation of drugs.  

PubMed

To clarify the effect of the surface charge of liposomes on percutaneous absorption, the permeation of liposomal drugs through rat skin was investigated in vitro and in vivo. Liposomes were prepared using egg yolk lecithin (EPC, phase transition temperature, -15 to -17 degrees C), cholesterol and dicetylphosphate (DP) or stearylamine (SA) (10:1:1, mol/mol). Also examined was the penetration behavior of positively and negatively charged liposomes, using a fluorescent probe (Nile Red). The in vitro penetration rate of melatonin (MT) entrapped in negatively charged liposomes was higher than that of positively charged ones (p<0.05). When the percutaneous absorption of ethosuximide (ES) encapsulated was estimated in vivo, the absorption of ES from negatively charged liposomes was slightly higher than that from positively charged liposomes. Additionally, the absorption of ES from both types of liposomes was superior to that from the lipid mixtures consisting of the same composition as the vesicles. The percutaneous absorption of betahistine (BH) from a gel formulation containing negatively charged liposomes of BH was much more than that from the formulation with positively charged ones, with 2-fold higher AUC (p<0.05). Histological studies revealed that the negatively charged liposomes diffused to the dermis and the lower portion of hair follicles through the stratum corneum and the follicles much faster than the positive vesicles at the initial time stage after application. Thus, the rapid penetration of negatively charged liposomes would contribute to the increased permeation of drugs through the skin. PMID:11378523

Ogiso, T; Yamaguchi, T; Iwaki, M; Tanino, T; Miyake, Y

2001-01-01

80

Nitric oxide (NO)-releasing statin derivatives, a class of drugs showing enhanced antiproliferative and antiinflammatory properties.  

PubMed

Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. Their pharmacological activity on atherosclerotic plaque stability and vascular inflammation appears to be mediated, at least in part, by nitric oxide (NO). With the aim of enhancing the nonlipid-lowering properties of selected statins, we introduced a NO-releasing moiety into the structure of pravastatin (NCX 6550) and fluvastatin (NCX 6553). NO release was evaluated as nitrosylhemoglobin adduct formation by using EPR spectroscopy in rat blood. Both compounds produced a linear time-dependent increase in nitrosylhemoglobin formation, which is consistent with slow NO release kinetics. In PC12 cells, unlike their native statins, both compounds stimulated cGMP formation (NCX 6550, EC(50) = 2.3 +/- 0.2 microM; NCX 6553, EC(50) = 2.7 +/- 0.2 microM). Moreover, NCX 6550 potently inhibited cell proliferation in rat aortic smooth muscle cells (IC(50) = 2.2 +/- 0.3 microM) with a mechanism that involved both the polyamine and HMG-CoA reductase signaling pathways. Hence, mevalonate or putrescine partially reverted the effects of NCX 6550 and their combination was fully effective. In RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide (1 microg/ml), NCX 6550, but not pravastatin, significantly decreased inducible NO synthase and cyclooxygenase-2 protein expression as well as nitrite accumulation. All together, the data show that the previously undescribed NO-releasing statins retain HMG-CoA reductase inhibitory activity and release bioactive NO slowly. Among the additional properties, compared with native statins, the NO-releasing statins show enhanced antiinflammatory effects. Thus, NO-releasing statins represent an interesting class of drugs having potential in the therapy of disorders associated with endothelial dysfunction and vascular inflammation. PMID:15173604

Ongini, Ennio; Impagnatiello, Francesco; Bonazzi, Albino; Guzzetta, Massimiliano; Govoni, Mirco; Monopoli, Angela; Del Soldato, Piero; Ignarro, Louis J

2004-06-01

81

Nitric oxide (NO)-releasing statin derivatives, a class of drugs showing enhanced antiproliferative and antiinflammatory properties  

PubMed Central

Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. Their pharmacological activity on atherosclerotic plaque stability and vascular inflammation appears to be mediated, at least in part, by nitric oxide (NO). With the aim of enhancing the nonlipid-lowering properties of selected statins, we introduced a NO-releasing moiety into the structure of pravastatin (NCX 6550) and fluvastatin (NCX 6553). NO release was evaluated as nitrosylhemoglobin adduct formation by using EPR spectroscopy in rat blood. Both compounds produced a linear time-dependent increase in nitrosylhemoglobin formation, which is consistent with slow NO release kinetics. In PC12 cells, unlike their native statins, both compounds stimulated cGMP formation (NCX 6550, EC50 = 2.3 ± 0.2 ?M; NCX 6553, EC50 = 2.7 ± 0.2 ?M). Moreover, NCX 6550 potently inhibited cell proliferation in rat aortic smooth muscle cells (IC50 = 2.2 ± 0.3 ?M) with a mechanism that involved both the polyamine and HMG-CoA reductase signaling pathways. Hence, mevalonate or putrescine partially reverted the effects of NCX 6550 and their combination was fully effective. In RAW 264.7 murine macrophage cells stimulated with lipopolysaccharide (1 ?g/ml), NCX 6550, but not pravastatin, significantly decreased inducible NO synthase and cyclooxygenase-2 protein expression as well as nitrite accumulation. All together, the data show that the previously undescribed NO-releasing statins retain HMG-CoA reductase inhibitory activity and release bioactive NO slowly. Among the additional properties, compared with native statins, the NO-releasing statins show enhanced antiinflammatory effects. Thus, NO-releasing statins represent an interesting class of drugs having potential in the therapy of disorders associated with endothelial dysfunction and vascular inflammation.

Ongini, Ennio; Impagnatiello, Francesco; Bonazzi, Albino; Guzzetta, Massimiliano; Govoni, Mirco; Monopoli, Angela; Del Soldato, Piero; Ignarro, Louis J.

2004-01-01

82

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm.  

PubMed

This study aimed to assess the antitumour effects, molecular mechanisms of action, and potential synergy of ruxolitinib with sorafenib, KNK437, dasatinib, and perifosine, in Philadelphia-negative chronic myeloproliferative neoplasms (MPN). Cytotoxic and cytostatic effects of the different compounds were determined in the JAK2 V617F-positive cell lines, HEL and Ba/F3 (JAK2V617F EPOR) , and in primary mononuclear and bone marrow CD34-positive cells from 19 MPN patients. Ruxolitinib [50% inhibitory concentration (IC50 )(PV)  = 15 nmol/l], as well as sorafenib (IC50 PV=8?mol/l), KNK437 (IC50 PV=100?mol/l ), and perifosine (IC50 PV=15?mol/l ), were able to inhibit proliferation in cell line models and in primary cells from MPN patients. Dasatinib, KNK437, and sorafenib showed a strong synergistic effect in combination with ruxolitinib [combination index (CI)(PV)  < 0·3]. Western blot confirmed that ruxolitinib blocked ERK, and consequently STAT5 activation, sorafenib inhibited ERK, P38 and STAT5, dasatinib blocked SRC and STAT5, and KNK437 decreased the stability of the JAK2 protein, reducing its expression. Inhibiting JAK2-related proliferative pathways has the potential to inhibit cell proliferation in MPNs. Furthermore, the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. PMID:23560534

Barrio, Santiago; Gallardo, Miguel; Arenas, Alicia; Ayala, Rosa; Rapado, Inmaculada; Rueda, Daniel; Jimenez, Ana; Albizua, Enriqueta; Burgaleta, Carmen; Gilsanz, Florinda; Martinez-Lopez, Joaquin

2013-06-01

83

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

Cancer.gov

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

84

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

PubMed Central

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

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

2014-01-01

85

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

Cancer.gov

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

86

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

PubMed

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

Niessen, W M A

2011-01-01

87

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

PubMed Central

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

Thomsen, Morgane; Caine, S. Barak

2011-01-01

88

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

PubMed Central

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

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

2012-01-01

89

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

PubMed

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

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

2013-01-01

90

Drug-tolerant cancer cells show reduced tumor-initiating capacity: depletion of CD44 cells and evidence for epigenetic mechanisms.  

PubMed

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

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

2011-01-01

91

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

Cancer.gov

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

92

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

PubMed Central

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.

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

93

Methadone use among HIV-positive injection drug users in a Canadian setting  

PubMed Central

We examined methadone maintenance therapy (MMT) use among HIV-positive injection drug users (IDU) in Vancouver. Among 353 participants, 199 (56.3%) were on MMT at baseline, and 48 initiated MMT during follow-up. Female gender (adjusted odds ratio [AOR] = 1.73, 95% CI: 1.14 – 2.62) and antiretroviral therapy use (AOR = 2.04, 95% CI: 1.46 – 2.86) were positively associated with MMT use, while frequent heroin injection (AOR = 0.34, 95% CI: 0.23–0.50), public injection (AOR = 0.76, 95% CI: 0.59 – 0.97), syringe borrowing (AOR = 0.54, 95% CI: 0.32 – 0.90), and non-fatal overdose (AOR = 0.58, 95% CI: 0.36 – 0.92) were negatively associated with MMT use. The rate of discontinuation of MMT was 12.46 (95% CI: 8.28 – 18.00) per 100 person years. Frequent heroin use (adjusted hazards ratio = 4.49, 95%CI: 1.81 – 11.13) was positively associated with subsequent discontinuation of MMT. These findings demonstrate the benefits of MMT among HIV-positive IDU and the need to improve access to and retention in MMT.

Pettes, Tyler; Wood, Evan; Guillemi, Silvia; Lai, Calvin; Montaner, Julio; Kerr, Thomas

2010-01-01

94

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

Microsoft Academic Search

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

Paolo Colombo; Ruggero Bettini; Nikolaos A. Peppas

1999-01-01

95

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

PubMed Central

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

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

2014-01-01

96

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

ERIC Educational Resources Information Center

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…

Valle, Maribel; Levy, Judith

2009-01-01

97

Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens.  

PubMed

The screening of new antibiotics against several bacterial strains often reveals unexpected occurrences of natural drug resistance. Two examples of this involve specific inhibitors of Staphylococcus aureus isoleucyl-transfer-RNA synthetase 1 (IleRS1) and, more recently, Streptococcus pneumoniae methionyl-tRNA synthetase 1 (MetRS1). In both cases, resistance is due to the presence of a second gene that encodes another synthetase (IleRS2 or MetRS2). Here, we show that both S. pneumoniae MetRS2 and S. aureus IleRS2 have closely related homologues in the Gram-positive bacterium Bacillus anthracis, the causative agent of anthrax. Furthermore, similar to drug-resistant pathogens, strains of B. anthracis and its closest relative, B. cereus, also have wild-type ileS1 and metS1 genes. Clostridium perfringens, the causative agent of gangrene, also has two metS genes, whereas Oceanobacillus iheyensis isolated from deep-sea sediments has a single ileS2-type gene. This study shows the importance of understanding complex evolutionary networks of ancient horizontal gene transfer for the development of novel antibiotics. PMID:12792655

Brown, James R; Gentry, Daniel; Becker, Julie A; Ingraham, Karen; Holmes, David J; Stanhope, Michael J

2003-07-01

98

Anti-retrovirals and immunosuppressive drug interactions in a HIV-positive patient after liver transplantation.  

PubMed

We report a case of drug-related toxicity after liver transplantation for hepatocellular carcinoma in a HIV-HCV co-infected patient. Before transplant the patient was on a triple antiretroviral therapy (zidovudine and lamivudine and efavirenz) with a stable CD4+ cell count >500 cells/microL. Liver transplantation was performed with a liver graft showing a 10% of macrosteatosis and with a graft-to-recipient body weight ratio of 1.3. Immunosuppression was achieved with tacrolimus, azathioprine and steroids. The antiretroviral therapy was resumed in the first postoperative day as the early graft function was in the normal range. After a few hours the patient showed myoglobinuria, rhabdomyolysis and a fast-deteriorating graft function. All drugs were withdrawn except steroids and an empiric therapy with riboflavin and glutathione was maintained for five days until myoglobinuria ended. Nevertheless the serum levels of tacrolimus remained in the therapeutic range for six days when it was reintroduced at a reduced dosage (0.01 mg/kg/die). The postoperative course was complicated by tense ascites and severe hyperbilirubinemia without any rejection episodes. The patient was discharged 48 days post-transplantation with a good liver function. During the following year no signs of aggressive HCV-HIV recurrences were observed and the patient is maintaining a CD4+ cells count >400 without antiretroviral therapy. PMID:15143883

Antonini, Mario; Ettorre, Giuseppe Maria; Vennarecci, Giovanni; D'Offizi, Gianpiero; Narciso, Pasquale; Del Nonno, Franca; Perracchio, Letizia; Visco, Giuseppe; Santoro, Eugenio

2004-01-01

99

[123I]-beta-CIT SPECT imaging shows reduced thalamus-hypothalamus serotonin transporter availability in 24 drug-free obsessive-compulsive checkers.  

PubMed

Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus-hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I]-beta-CIT brain binding was used (V''(3)=(thalamus and hypothalamus-cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38+/-0.19 vs 1.69+/-0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=-0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [(123)I]-beta-CIT binding in the thalamus-hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD. PMID:17192774

Zitterl, Werner; Aigner, Martin; Stompe, Thomas; Zitterl-Eglseer, Karin; Gutierrez-Lobos, Karin; Schmidl-Mohl, Brigitte; Wenzel, Thomas; Demal, Ulrike; Zettinig, Georg; Hornik, Kurt; Thau, Kenneth

2007-08-01

100

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

PubMed

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

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

2014-06-01

101

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

PubMed Central

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.

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

2011-01-01

102

Early appropriate therapy of Gram-positive bloodstream infections: the conservative use of new drugs.  

PubMed

Among the Gram-positive organisms, meticillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium represent the biggest therapeutic hurdles. The evolution of MRSA exemplifies the genetic adaptation of an organism into a first-class multidrug-resistant pathogen. Glycopeptides such as vancomycin have been the treatment of choice for MRSA, but poor outcomes have frequently been reported, particularly among isolates with higher minimum inhibitory concentrations (MICs) within the susceptible range (< or =2 mg/L). Further more, vancomycin's limitations as an antibacterial agent include slow bactericidal activity and relatively poor tissue penetration. Inadequate dosing may, however, contribute to vancomycin's poor performance; the standard recommendation for trough concentrations of 5-10 mg/L is inadequate for serious infections such as bacteraemia and endocarditis. Trough levels of 15-20 mg/L are probably necessary; however they are often associated with increased nephrotoxicity. Despite the recent dramatic reduction in antibiotic research by pharmaceutical companies, a few compounds have been developed to treat Gram-positive infections. Quinupristin-dalfopristin, although shown to have in vitro activity against MRSA, is not approved by the US Food and Drug Administration for the treatment of MRSA, and cannot be recommended for the treatment of S. aureus bacteraemia, except under exceptional circumstances. Although linezolid and tigecycline may be useful in specific situations, they cannot be routinely recommended for the treatment of MRSA bacteraemia because of safety concerns and very limited available clinical data. Daptomycin has recently been proven to be effective and well tolerated for meticillin-sensitive S. aureus and MRSA bacteraemia, including right-sided endocarditis. PMID:19931814

Grossi, Paolo A

2009-01-01

103

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

PubMed Central

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

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

104

NF-?B activation-induced anti-apoptosis renders HER2-positive cells drug resistant and accelerates tumor growth.  

PubMed

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

Bailey, Shannon T; Miron, Penelope L; Choi, Yoon J; Kochupurakkal, Bose; Maulik, Gautam; Rodig, Scott J; Tian, Ruiyang; Foley, Kathleen M; Bowman, Teresa; Miron, Alexander; Brown, Myles; Iglehart, J Dirk; Biswas, Debajit K

2014-03-01

105

The impact of incarceration upon adherence to HIV treatment among HIV-positive injection drug users: a qualitative study  

Microsoft Academic Search

Introduction. HIV-positive injection drug users (IDU) often do not derive the full benefits of highly active antiretroviral therapy (HAART). Among IDU, recent incarceration has been associated with discontinuation of HAART for non-clinical reasons. We sought to qualitatively evaluate experiences with HAART among HIV-positive IDU who had been recently incarcerated within provincial prisons in British Columbia in order to identify factors

Will Small; Evan Wood; Glenn Betteridge; Julio Montaner; Thomas Kerr

2009-01-01

106

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

Microsoft Academic Search

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

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

2003-01-01

107

Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy  

PubMed Central

To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/?l were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ?250 cells/mm3 with comorbid conditions.

Srikanth, B. Akshaya; Babu, S. Chandra; Yadav, Harlokesh Narayan; Jain, Sunil Kumar

2012-01-01

108

Field, Genetic, and Modeling Approaches Show Strong Positive Selection Acting upon an Insecticide Resistance Mutation in Anopheles gambiae s.s.  

PubMed Central

Alleles subject to strong, recent positive selection will be swept toward fixation together with contiguous sections of the genome. Whether the genomic signatures of such selection will be readily detectable in outbred wild populations is unclear. In this study, we employ haplotype diversity analysis to examine evidence for selective sweeps around knockdown resistance (kdr) mutations associated with resistance to dichlorodiphenyltrichloroethane and pyrethroid insecticides in the mosquito Anopheles gambiae. Both kdr mutations have significantly lower haplotype diversity than the wild-type (nonresistant) allele, with kdr L1014F showing the most pronounced footprint of selection. We complement these data with a time series of collections showing that the L1014F allele has increased in frequency from 0.05 to 0.54 in 5 years, consistent with a maximum likelihood–fitted selection coefficient of 0.16 and a dominance coefficient of 0.25. Our data show that strong, recent positive selective events, such as those caused by insecticide resistance, can be identified in wild insect populations.

Lynd, Amy; Weetman, David; Barbosa, Susana; Egyir Yawson, Alexander; Mitchell, Sara; Pinto, Joao; Hastings, Ian; Donnelly, Martin J.

2010-01-01

109

[Two news drugs (ivacaftor & bedaquiline), one biomarker (florbetapir) and a re-positioned drug (propranolol) on the market].  

PubMed

Among the new molecular entities approved by the EMEA and the FDA in 2012, four have caught our attention for their significant contribution to the health of patient. First of all, among the notable 2012 approvals, is ivacaftor or Kalydeco(®). This is the first treatment that targets one of the gene defects that is underlying cause of cystic fibrosis. This is also an example of the promise of personalized medicine. The benefits with bedaquiline or Sirturo(®) are its ability to likely provide clinically relevant activity as part of multi-drug regimens against tuberculosis (TB) based on clinical data in multi-drug resistant tuberculosis (MDR TB) patients, who were defined as being at least resistant against the two major tuberculostatic medicines (isaoniazide and rifampicine). On December 2012 and then, on December 2013, the FDA and European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended granting a conditional marketing authorization for Sirturo(®) (bedaquiline), respectively, for use as part of a combination therapy for pulmonary multidrug resistant tuberculosis in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. Amyvid(®), which is a solution for injection that contains the active substance florbetapir ((18)F), is a radiopharmaceutical that emits low amounts of radiation and works by targeting and attaching to ?-amyloid plaques in the brain. This enables doctors to know whether or not significant amount of plaques are present in order to know if the patient is unlikely or not, to have Alzheimer's disease. Finally, the last topics addresses the propranolol, which is a beta-blocker, used alone or together with other medicines to treat high blood pressure. Propranolol is gaining a new lease of life for treating infantile hemangioma. PMID:24997884

Monneret, C

2014-07-01

110

Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy.  

PubMed

Anti-angiogenic therapy is a potential chemotherapeutic strategy for the treatment of drug resistant cancers. However, a method for delivering such drugs to tumor endothelial cells remains to be a major impediment to the success of anti-angiogenesis therapy. We designed liposomes (LPs) with controlled diameter of around 300 nm, and modified them with a specific ligand and a cell penetrating peptide (CPP) (a dual-ligand LP) for targeting CD13-expressing neovasculature in a renal cell carcinoma (RCC). We modified the LPs with an NGR motif peptide on the top of poly(ethylene glycol) and tetra-arginine (R4) on the surface of the liposome membrane as a specific and CPP ligand, respectively. The large size prevented extravasation of the dual-ligand LP, which allowed it to associate with target vasculature. While a single modification with either the specific or CPP ligand showed no increase in targetability, the dual-ligand enhanced the amount of delivered liposomes after systemic administration to OS-RC-2 xenograft mice. The anti-tumor activity of a dual-ligand LP encapsulating doxorubicin was evaluated and the results were compared with Doxil, which is clinically used to target tumor cells. Even though Doxil showed no anti-tumor activity, the dual-ligand LP suppressed tumor growth because the disruption of tumor vessels was efficiently induced. The comparison showed that tumor endothelial cells (TECs) were more sensitive to doxorubicin by 2 orders than RCC tumor cells, and the disruption of tumor vessels was efficiently induced. Collectively, the dual-ligand LP is promising carrier for the treatment of drug resistant RCC via the disruption of TECs. PMID:22728515

Takara, Kazuhiro; Hatakeyama, Hiroto; Kibria, Golam; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi

2012-08-20

111

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

PubMed Central

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.

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

2008-01-01

112

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 Central

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 wcith the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results.

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

2013-01-01

113

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

PubMed Central

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

2014-01-01

114

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

PubMed

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

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

2014-01-01

115

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

Microsoft Academic Search

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

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

2009-01-01

116

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

PubMed

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

2014-04-01

117

Responses to Positive Results from Suspicionless or Random Drug Tests in U.S. Public School Districts  

PubMed Central

Background Little is known about the context in which school-based suspicionless or random drug testing (SRDT) occurs. The primary purpose of the current study is to describe school districts’ responses to students’ first positive result in districts with SRDT programs. Methods Data were collected in spring 2005 from 1612 drug prevention coordinators in a nationally representative sample of 1922 school districts (83.9% response rate), of which 205 districts reported SRDT in high school grades. Results Respondents reported an array of consequences for students with an initial positive SRDT, including requiring parents or guardians to meet with school officials (88.4%), and requiring students to participate in an education, counseling, or treatment program (60.8%). However, some districts also reported consequences contraindicated by federal advisory guides, such as notifying law enforcement officials (45.1%) and suspending the student from an athletic team (65.0%) or from school (31.0%). Some respondents may have conflated their districts’ responses to for-cause and random tests. Districts generally had available key services for students testing positive, including professional counseling for substance use problems (87.3%) and referrals to counseling services (91.9%). Conclusions More understanding is needed of schools’ responses to students who test positive following the administration of SRDT, available advisory guides concerning best practices should be more effectively disseminated, and appropriate training and technical assistance should be available to schools with SRDTs.

Vincus, Amy A.; Ennett, Susan T.; Hanley, Sean; Bowling, J. Michael; Yacoubian, George S.; Rohrbach, Louise A.

2010-01-01

118

Positive relationship between dietary fat, ethanol intake, triglycerides and hypothalamic peptides: Counteraction by lipid-lowering drugs  

PubMed Central

Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TG), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TG and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected with ethanol (1 g/kg i.p.) and tested in terms of their preference for a high-fat compared to low-fat diet, showed a significant increase in their fat preference, compared to rats injected with saline, in measures of 2 h and 24 h intake. Experiment 2 tested the relationship of circulating TG in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol vs. water and given acute meal tests (25 kcal) of a high-fat vs. low-fat diet. Levels of TG were elevated in response to both chronic drinking of ethanol vs. water and acute eating of a high-fat vs. low-fat meal. Most importantly, ethanol and a high-fat diet showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a low-fat diet (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After administration of gemfibrozil (50 mg/kg i.g.) compared to vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide OX, in the perifornical lateral hypothalamus. These results support the existence of a vicious cycle between ethanol and fat whereby each nutrient stimulates intake of the other. Within this vicious cycle, ethanol and fat act synergistically to increase TG levels, which in turn stimulate peptides that promote further consumption, and these phenomena are reversed by gemfibrozil, which lowers TG levels.

Barson, Jessica R.; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F.; Bocarsly, Miriam E.; Hoebel, Bartley G.; Leibowitz, Sarah F.

2009-01-01

119

FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML  

Microsoft Academic Search

An appealing therapeutic target in AML is constitutively activated, mutant FLT3, which is expressed in a subpopulation of AML patients and is generally a poor prognostic indicator in patients under the age of 65. There are currently several FLT3 inhibitors that are undergoing clinical investigation. However, the discovery of drug-resistant leukemic blast cells in FLT3 inhibitor-treated AML patients has prompted

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

2009-01-01

120

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

PubMed Central

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

Acuna-Alonzo, Victor; Flores-Dorantes, Teresa; Kruit, Janine K.; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hunemeier, Tabita; Moreno-Estrada, Andres; Ortiz-Lopez, Ma Guadalupe; Villamil-Ramirez, Hugo; Leon-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramirez-Jimenez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D.; de Angeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo; Bustos-Arriaga, Jose; Cedillo-Barron, Leticia; Gomez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P.; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vazquez, Adriana; Gonzalez-Martin, Antonio; Gorostiza, Amaya; Bonatto, Sandro L.; Rodriguez-Cruz, Maricela; Wang, Li; Tusie-Luna, Teresa; Aguilar-Salinas, Carlos A.; Lisker, Ruben; Moises, Regina S.; Menjivar, Marta; Salzano, Francisco M.; Knowler, William C.; Bortolini, M. Catira; Hayden, Michael R.; Baier, Leslie J.; Canizales-Quinteros, Samuel

2010-01-01

121

Mental health and social support among HIV-positive injection drug users and their caregivers in China.  

PubMed

The burden of HIV/AIDS in China is due to injection drug use. Non-clinical caregivers provide much of the care for HIV patients but are often not included in HIV care or research. The objective of this study is to examine the relationships between the caregiver context and mental health of HIV-positive injection drug users and their caregivers. We interviewed 96 patient-caregiver dyads using quantitative methods. A conceptual model was developed as a framework for multivariate linear regression modeling. The strongest predictor of poor patient mental health was lack of social support, which was largely determined by the caregiver's stigma towards HIV/AIDS and caregiver burden. Patient disability and caregiver burden were the primary predictors of poor caregiver mental health. The interrelated nature of caregiver and patient mental health supports the inclusion of caregiver health into the patient's HIV/AIDS treatment to maximize support provision and health for the patient and caregiver. PMID:23283579

Greene, M Claire; Zhang, Jianping; Li, Jianhua; Desai, Mayur; Kershaw, Trace

2013-06-01

122

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

SciTech Connect

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

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

1994-06-01

123

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

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

124

An Epstein-Barr virus positive natural killer lymphoma xenograft derived for drug testing.  

PubMed

Natural killer (NK) lymphomas occurring more frequently in the Far East and South America respond poorly to anthracycline-based regimens. Here we report an in vivo NK lymphoma xenograft (NK-S1) derived from the testicular metastasis of a patient with an extranodal NK lymphoma (nasal type). The NK-S1 xenograft, established in severe combined immune deficient (SCID) mice retained the same imunophenotypic features as the original tumor. NK-S1 disseminated intra-abdominally to the testis, intestine and liver. Although doxorubicin, rapamycin, bevacizumab, rapamycin-doxorubicin, and bevacizumab-doxorubicin had no effects on the growth of subcutaneous NK-S1 xenografts, intraperitoneal (IP) delivery of cyclophosphamide caused complete tumor regression; this tumor regression was associated with apoptosis, upregulation of activated caspase-3, and cleaved Poly(ADP-ribose) polymerase (PARP). In an IP model of NK lymphoma, cyclophosphamide also prolonged the survival of mice and potently inhibited tumor dissemination and ascites formation. Our data suggest that the NK-S1 xenograft is a useful tool for screening preclinical drugs, and cyclophosphamide may be a useful drug for the treatment of this disease. PMID:18452087

Loong, Susan Li Er; Hwang, Jacqueline Siok Gek; Lim, Soon-Thye; Yap, Swee Peng; Tao, Miriam; Chong, Tsung-Wen; Tan, Leonard Hwan Cheong; Huynh, Hung

2008-06-01

125

Drugs.  

ERIC Educational Resources Information Center

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.…

Hurst, Hunter, Ed.; And Others

1984-01-01

126

Comparison of two drug regimens upon clinical outcome among renal transplant recipients with positive flow cytometric crossmatches.  

PubMed

Renal transplant recipients with positive flow cytometric crossmatches (FCXM) face greater risk of early rejection and graft failure. It is clear that the pharmacologic needs of this high risk group have not been identified. We retrospectively compared the impact of two drug regimens upon early rejection and 5 yr actuarial survival among 324 primary cadaveric transplant recipients with positive and negative FCXM. Patients received either Regimen I (OKT3 induction, cyclosporine and steroids) or Regimen II (mycophenolate mofetil with cyclosporine or Prograf). Recipient gender, age, disease etiology, ethnic distribution and cytotoxic panel reactive antibody (PRA) were equivalent between regimens (p=ns). With Regimen I, the incidence of rejection was greater for FCXM positive vs. FCXM negative patients (51 vs. 21%, p=0.001). In contrast, with Regimen II the incidence of rejection for FCXM positive and FCXM negative patients was equivalent (18 vs. 12%, p=ns) and lower than patients treated with Regimen I (p < 0.01). Ethnic variation was only observed with Regimen I in which African Americans with positive FCXM had more rejections than Caucasians (60 vs. 45%, p < 0.05). Five-year actuarial survival was lower for FCXM positive vs. FCXM negative patients treated with Regimen I (40 vs. 75%, p=0.0006) or Regimen 2 (60 vs. 90%, p=0.001). Allograft survival was equivalent (p=ns) among FCXM positive individuals receiving Regimen I or II. However, allograft survival among FCXM negative individuals improved with Regimen II (p < 0.05). Ethnic variation in survival was not observed with either regimen (p=ns). PMID:12099986

Kimball, Pam; Wagner, Beth; King, Anne; Fisher, Robert A; Dawson, Sherfield; Cotterell, Adrian; Posner, Marc

2002-08-01

127

Prevalence and Drug Resistance Patterns of Mycobacterium tuberculosis among New Smear Positive Pulmonary Tuberculosis Patients in Eastern Ethiopia.  

PubMed

The study aimed at determining the prevalence and drug resistance patterns of Mycobacterium tuberculosis among new smear positive pulmonary tuberculosis patients visiting TB diagnosis and treatment facilities at selected health facilities in eastern Ethiopia. A cross-sectional study was conducted between October 2011 and May 2013. A total of 408 new adult pulmonary TB patients (? 18 years) were enrolled in this study. Three consecutive sputum samples (spot, morning, and spot) were collected from each patient and transported to the Armauer Hansen Research Institute TB laboratory located in Addis Ababa for culture on Lowenstein Jensen slant media. DST was performed on 357 (87.5%) of the patient samples for isoniazid (H), rifampicin (R), ethambutol (E), and streptomycin (S) using the standard proportion method. The rate of resistance to any one drug was 23%. Any resistance to H, S, R, and E was 14%, 11.5%, 2.8%, and 0.3%, respectively. The highest proportion of monoresistance was observed against H (9.5%). MDRTB was detected in 1.1% of the patients. Any drug resistance was associated with HIV infection (COR = 3.7, 95% CI 1.905-7.222) (P = 0.000). Although the prevalence of MDRTB is relatively low in the study area, high prevalence of H resistance is a serious concern demanding close monitoring. Expanding diagnostic capacity for mycobacterial culture and DST is a vital step in this regard. PMID:24834351

Seyoum, Berhanu; Demissie, Meaza; Worku, Alemayehu; Bekele, Shiferaw; Aseffa, Abraham

2014-01-01

128

Current Cigarette Smoking Among HIV-Positive Current and Former Drug Users: Associations with Individual and Social Characteristics.  

PubMed

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

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

2014-07-01

129

Prevalence and Drug Resistance Patterns of Mycobacterium tuberculosis among New Smear Positive Pulmonary Tuberculosis Patients in Eastern Ethiopia  

PubMed Central

The study aimed at determining the prevalence and drug resistance patterns of Mycobacterium tuberculosis among new smear positive pulmonary tuberculosis patients visiting TB diagnosis and treatment facilities at selected health facilities in eastern Ethiopia. A cross-sectional study was conducted between October 2011 and May 2013. A total of 408 new adult pulmonary TB patients (? 18 years) were enrolled in this study. Three consecutive sputum samples (spot, morning, and spot) were collected from each patient and transported to the Armauer Hansen Research Institute TB laboratory located in Addis Ababa for culture on Lowenstein Jensen slant media. DST was performed on 357 (87.5%) of the patient samples for isoniazid (H), rifampicin (R), ethambutol (E), and streptomycin (S) using the standard proportion method. The rate of resistance to any one drug was 23%. Any resistance to H, S, R, and E was 14%, 11.5%, 2.8%, and 0.3%, respectively. The highest proportion of monoresistance was observed against H (9.5%). MDRTB was detected in 1.1% of the patients. Any drug resistance was associated with HIV infection (COR = 3.7, 95% CI 1.905–7.222) (P = 0.000). Although the prevalence of MDRTB is relatively low in the study area, high prevalence of H resistance is a serious concern demanding close monitoring. Expanding diagnostic capacity for mycobacterial culture and DST is a vital step in this regard.

Seyoum, Berhanu; Demissie, Meaza; Worku, Alemayehu; Bekele, Shiferaw; Aseffa, Abraham

2014-01-01

130

Illicit Drug Use, Depression and their Association with Highly Active Antiretroviral Therapy in HIV-Positive Women  

PubMed Central

Background We examined the interaction of illicit drug use and depressive symptoms, and how they affect the subsequent likelihood of highly active antiretroviral therapy (HAART) use among women with HIV/AIDS. Methods Subjects included 1,710 HIV-positive women recruited from six sites in the U.S. including Brooklyn, Bronx, Chicago, Los Angeles, San Francisco/Bay Area, and Washington, DC. Cases of probable depression were identified using depressive symptom scores on the Centers for Epidemiologic Studies Depression Scale. Crack, cocaine, heroin, and amphetamine use were self-reported at 6-month time intervals. We conducted multivariate logistic random regression analysis of data collected during sixteen waves of semiannual interviews conducted from April 1996 through March 2004. Results We found an interaction effect between illicit drug use and depression that acted to suppress subsequent HAART use, controlling for virologic and immunologic indicators, socio-demographic variables, time, and study site. Conclusions This is the first study to document the interactive effects of drug use and depressive symptoms on reduced likelihood of HAART use in a national cohort of women. Since evidence-based behavioral health and antiretroviral therapies for each of these three conditions are now available, comprehensive HIV treatment is an achievable public health goal.

Cook, Judith A.; Grey, Dennis D.; Burke-Miller, Jane K.; Cohen, Mardge H.; Vlahov, David; Kapadia, Farzana; Wilson, Tracey E.; Cook, Robert; Schwartz, Rebecca; Golub, Elizabeth; Anastos, Kathryn; Ponath, Claudia; Goparaju, Lakshmi; Levine, Alexandra

2014-01-01

131

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

PubMed Central

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

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

2013-01-01

132

Existence of Leukemic Clones Resistant to Both Imatinib Mesylate and Rituximab before Drug Therapies in a Patient with Philadelphia Chromosome-Positive Acute Lymphocytic Leukemia  

Microsoft Academic Search

Imatinib mesylate and rituximab are molecularly targeted drugs against the BCR-ABL fusion protein and the CD20 antigen, respectively.\\u000a Although these drugs have excellent anticancer effects, a major concern is drug resistance. We have investigated the case\\u000a of a patient with Philadelphia chromosome-positive and CD20+ acute lymphocytic leukemia who acquired resistance to imatinib and rituximab. Imatinib therapy resulted in prompt cytogenetic

Takaaki Hato; Jun Yamanouchi; Tatsushiro Tamura; Norimasa Hojo; Yasunari Niiya; Masashi Kohno; Shiro Bando; Yoshihiro Yakushijin; Kiyonori Takada; Ikuya Sakai; Masaki Yasukawa; Shigeru Fujita

2004-01-01

133

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

PubMed

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

Gujral, B B

1983-01-01

134

Pharmacologic Management of Osteoarthritis-Related Pain in Older Adults: A Review Shows that Many Drug Therapies Provide Small-to-Modest Pain Relief.  

PubMed

Because pain is a common and debilitating symptom of osteoarthritis in older adults, the authors reviewed data on the efficacy and safety of commonly used oral, topical, and intraarticular drug therapies in this population. A search of several databases found that most studies have focused on knee osteoarthritis and reported only short-term outcomes. Also, treatment efficacy was found to vary by drug class; the smallest effect was observed with acetaminophen and the largest with opioids and viscosupplements. Acetaminophen and topical agents had the best safety profiles, whereas oral nonsteroidal antiinflammatory drugs and opioids had the worst. Little data were available on patients ages 75 years old and older and on patients from diverse racial and ethnic groups. Most drug therapies gave mild-to-moderate pain relief; their long-term safety and efficacy and their effects in diverse populations (particularly older adults) remain undetermined. PMID:23874257

Reid, M Carrington; Shengelia, Rouzi; Parker, Samantha J

2012-07-01

135

Accuracy and potential usefulness of triplex real-time PCR for improving antibiotic treatment of patients with blood cultures showing clustered gram-positive cocci on direct smears.  

PubMed

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

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

2008-06-01

136

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

NASA Astrophysics Data System (ADS)

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

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

137

Bidirectional microdialysis in vivo shows differential dopaminergic potency of cocaine, procaine and lidocaine in the nucleus accumbens using capillary electrophoresis for calibration of drug outward diffusion  

Microsoft Academic Search

Cocaine and two other local anesthetics were applied directly into the nucleus accumbens for 20 min by diffusion from a 4 mm microdialysis probe in freely moving rats. Cocaine (7.3 mM) increased the extracellular concentration of dopamine (DA). Equimolar procaine did also, but was not as potent as cocaine. Equimolar lidocaine had no effect. The concentration of these drugs outside

Luis Hernandez; Norberto A. Guzman; Bartley G. Hoebel

1991-01-01

138

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

Microsoft Academic Search

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

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

1995-01-01

139

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

PubMed Central

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.

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

2008-01-01

140

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

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

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

141

In vivo establishment and characterization of a paclitaxel-resistant human ovarian cancer cell line showing enhanced growth properties and drug-resistance only in vivo  

Microsoft Academic Search

Purpose In order to establish a more faithful model of clinically recurrent ovarian cancer after paclitaxel-based chemotherapy, a paclitaxel-resistant human ovarian cancer cell line was established in vivo, and its biological profiles were compared with the conventional in vitro established drug-resistant cell line. Methods An in vivo paclitaxel-resistant subline (OM1\\/Tvivo) was established from the parental human ovarian cancer cell line

Kaoru Okugawa; Hiroaki Kobayashi; Toshio Hirakawa; Takanori Sonoda; Tomonori Ogura; Hitoo Nakano

2004-01-01

142

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

Microsoft Academic Search

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

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

2011-01-01

143

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

PubMed

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

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

2014-07-01

144

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

NASA Astrophysics Data System (ADS)

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

Ikuzawa, Masayuki; Akiduki, Saori; Asashima, Makoto

145

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

PubMed Central

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

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

2013-01-01

146

"The Show"  

ERIC Educational Resources Information Center

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…

Gehring, John

2004-01-01

147

Tracking the extramedullary PML-RAR?-positive cell reservoirs in a preclinical model: biomarker of long-term drug efficacy.  

PubMed

Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene-specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR?) oncogene. Kaplan-Meier survival analysis according to the peripheral blood PML-RAR? normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p < 0.0001) survival advantage. Furthermore, a PCR assay was used to assess various tissues and organs for the presence of PML-RAR?-positive cells in long-term survivors (n = 15). As expected, the majority of mice (n = 10) had no measurable tissue level of PML-RAR?. However, five mice showed a weak positive signal in both the brain and spleen (n = 2), in the brain only (n = 2) and in the spleen only (n = 1). Thus tracking the oncogene-positive cells in long-term survivors reveals for the first time that extramedullary PML-RAR?-positive cell reservoirs such as the brain may persist and be involved in relapses. PMID:22906630

Pokorna, Katerina; Le Pogam, Carole; Chopin, Martine; Balitrand, Nicole; Reboul, Murielle; Cassinat, Bruno; Chomienne, Christine; Padua, Rose Ann; Pla, Marika

2013-02-01

148

Interventions for Seropositive Injectors???Research and Evaluation: An Integrated Behavioral Intervention With HIV-Positive Injection Drug Users to Address Medical Care, Adherence, and Risk Reduction  

Microsoft Academic Search

Background: Behavioral interventions to address the complex medical and HIV risk reduction needs of HIV-seropositive (HIV- positive) injection drug users (IDUs) are urgently needed. We de- scribe the development of Interventions for Seropositive Injectors— Research and Evaluation (INSPIRE), a randomized controlled trial of an integrated intervention for HIV-positive IDUs, and the character- istics of the baseline sample. Methods: HIV-positive IDUs

David W. Purcell; Lisa R. Metsch; Mary Latka; Scott Santibanez; Lois Eldred; Carl A. Latkin

2004-01-01

149

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

PubMed Central

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

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

2012-01-01

150

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

PubMed

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

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

2012-10-01

151

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

PubMed Central

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

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

2008-01-01

152

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

PubMed

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

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

2008-09-12

153

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

PubMed

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

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

2014-06-01

154

In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans.  

PubMed Central

Inhibition of in vitro colony formation of human hematopoietic progenitors (CFU-granulocyte-macrophage, burst-forming unit-erythroid) by the antiviral nucleoside drugs alovudine, zalcitabine, zidovudine, ganciclovir, stavudine, didanosine, lamivudine, and acyclovir was measured. Significant correlations between in vitro 50% inhibitory concentrations and the daily human exposures (area under the concentration-time curve from 0 to 24 h; in micromolar.hour) of these chronically administered drugs in human immunodeficiency virus-positive patients that induced neutropenia or anemia were demonstrated by both linear regression and Spearman rank-order analyses. These quantitative correlations allow estimation of the exposure at which bone marrow toxicity may occur with candidate compounds.

Dornsife, R E; Averett, D R

1996-01-01

155

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

Microsoft Academic Search

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

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

2006-01-01

156

Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.  

PubMed

Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-stimulated 45Ca2+ influx in primary cultures of cerebellar granule cells. Nootropic drugs increased the efficacy but not the potency of AMPA and their action persisted in the presence of the voltage-sensitive calcium channel blocker nifedipine. Potentiation by oxiracetam was specific for AMPA receptor-mediated signal transduction, as the drug changed neither the stimulation of 45Ca2+ influx by kainate or N-methyl-D-aspartate nor the activation of inositol phospholipid hydrolysis elicited by quisqualate or (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid. Piracetam, aniracetam, and oxiracetam increased the maximal density of the specific binding sites for [3H]AMPA in synaptic membranes from rat cerebral cortex. Taken collectively, these results support the view that nootropic drugs act as positive modulators of AMPA-sensitive glutamate receptors in neurons. PMID:1372342

Copani, A; Genazzani, A A; Aleppo, G; Casabona, G; Canonico, P L; Scapagnini, U; Nicoletti, F

1992-04-01

157

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

PubMed Central

We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal activities of the resultant SC4 'peptide-amphiphile' molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), including S. aureus strains resistant to conventional antibiotics, but little or no increase in bactericidal activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fatty acid conjugation improved endotoxin (lipopolysaccharide) neutralization by 3- to 6-fold. Although acylation somewhat increased lysis of human erythrocytes, it did not increase lysis of endothelial cells, and the haemolytic effects occurred at concentrations 10- to 100-fold higher than those required for bacterial cell lysis. For insight into the mechanism of action of SC4 peptide-amphiphiles, CD, NMR and fluorescence spectroscopy studies were performed in micelle and liposome models of eukaryotic and bacterial cell membranes. CD indicated that SC4 peptide-amphiphiles had the strongest helical tendencies in liposomes mimicking bacterial membranes, and strong membrane integration of the SC4 peptide-amphiphiles was observed using tryptophan fluorescence spectroscopy under these conditions; results that correlated with the increased bactericidal activities of SC4 peptide-amphiphiles. NMR structural analysis in micelles demonstrated that the two-thirds of the peptide closest to the fatty acid tail exhibited a helical conformation, with the positively-charged side of the amphipathic helix interacting more with the model membrane surface. These results indicate that conjugation of a fatty acid chain to the SC4 peptide enhances membrane interactions, stabilizes helical structure in the membrane-bound state and increases bactericidal potency.

Lockwood, Nathan A; Haseman, Judith R; Tirrell, Matthew V; Mayo, Kevin H

2004-01-01

158

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

PubMed

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

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

2013-12-01

159

Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens  

Microsoft Academic Search

The screening of new antibiotics against several bacterial strains often reveals unexpected occurrences of natural drug resistance. Two examples of this involve specific inhibitors of Staphylococcus aureus isoleucyl-transfer-RNA synthetase 1 (IleRS1) and, more recently, Streptococcus pneumoniae methionyl-tRNA synthetase 1 (MetRS1). In both cases, resistance is due to the presence of a second gene that encodes another synthetase (IleRS2 or MetRS2).

Daniel Gentry; Julie A. Becker; Karen Ingraham; David J. Holmes; James R. Brown; Michael J. Stanhope

2003-01-01

160

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

PubMed Central

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

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

2014-01-01

161

Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels  

Microsoft Academic Search

We have used agarose gel to develop a robust model of the intraparenchymal brain tissues for the purpose of simulating positive-pressure infusion of therapeutic agents directly into the brain. In parallel with that effort, we have synthesized a mathematical description of the infusion process on the basis of a poroelastic theory for the swelling of the tissues under the influence

Zhi-Jian Chen; William C. Broaddus; Raju R. Viswanathan; Raghu Raghavan; George T. Gillies

2002-01-01

162

U.s. Food and drug administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive.  

PubMed

On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% [95% confidence intervals (CI), 52%-70%] with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The most common adverse reactions (?25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted on the basis of the high ORRs and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen. Clin Cancer Res; 20(8); 2029-34. ©2014 AACR. PMID:24573551

Malik, Shakun M; Maher, Virginia Ellen; Bijwaard, Karen E; Becker, Robert L; Zhang, Lijun; Tang, Shenghui W; Song, Pengfei; Liu, Qi; Marathe, Anshu; Gehrke, Brenda; Helms, Whitney; Hanner, Diane; Justice, Robert; Pazdur, Richard

2014-04-15

163

Ciprofloxacin-Induced Acute Generalized Exanthematous Pustulosis Mimicking Bullous Drug Eruption Confirmed by a Positive Patch Test  

Microsoft Academic Search

We report the case of an 80-year-old woman presenting with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP) confirmed by a positive patch test. Cutaneous morphology, course and histological findings were consistent with a definite diagnosis according to the AGEP validation score of the EuroSCAR study group. We point to the rarity of quinolone-induced AGEP and discuss immunological mechanisms, the value of

P. Häusermann; K. Scherer; M. Weber; A. J. Bircher

2005-01-01

164

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

PubMed Central

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).

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

2012-01-01

165

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

PubMed Central

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

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

2013-01-01

166

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

PubMed

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

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

2012-07-01

167

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

PubMed Central

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

Cheng, Kejun; Rice, Kenner C.

2013-01-01

168

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 Central

SLC6A14, also known as ATB0,+, 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.

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

2011-01-01

169

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

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

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

170

Using Electronic Drug Monitor Feedback to Improve Adherence to Antiretroviral Therapy Among HIV-Positive Patients in China  

PubMed Central

Effective antiretroviral therapy (ART) requires excellent adherence. Little is known about how to improve ART adherence in many HIV/AIDS-affected countries, including China. We therefore assessed an adherence intervention among HIV-positive patients in southwestern China. Eighty subjects were enrolled and monitored for 6 months. Sixty-eight remaining subjects were randomized to intervention/control arms. In months 7–12, intervention subjects were counseled using EDM feedback; controls continued with standard of care. Among randomized subjects, mean adherence and CD4 count were 86.8 vs. 83.8% and 297 vs. 357 cells/?l in intervention vs. control subjects, respectively. At month 12, among 64 subjects who completed the trial, mean adherence had risen significantly among intervention subjects to 96.5% but remained unchanged in controls. Mean CD4 count rose by 90 cells/?l and declined by 9 cells/?l among intervention and control subjects, respectively. EDM feedback as a counseling tool appears promising for management of HIV and other chronic diseases.

DeSilva, Mary Bachman; Hamer, Davidson H.; Xu, Keyi; Zhang, Jianbo; Li, Tao; Wilson, Ira B.; Gill, Christopher J.

2009-01-01

171

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

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

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

172

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

PubMed

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

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

2014-03-01

173

Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: Analysis from a national drug-resistance database (ARCA).  

PubMed

Rilpivirine (RPV) is a novel NNRTI with a mutational pattern different from first-generation drugs of the same class: 16 resistance-associated mutations (RAM) are listed, but the combination E138K?+?M184I seems to be the most important. Aims of the present study were to evaluate the prevalence of these RAMs in Italian HIV-1 infected patients and to assess if previous drug history could represent a risk to develop RPV-related RAMs. The analysis was performed using the ARCA database, which contains data on resistance and therapy from subjects throughout Italy. Prevalence of RPV-associated and first-generation NNRTI-associated RAMs was evaluated. Linear regression model, odds ratio and 95% Confidence Interval were used to assess factors associated with the development of RPV RAMs, substitutions at position 184 and their combinations. A total of 8,067 tests were selected within the database. In Italian HIV-positive HAART-naïve patients, prevalence of the main RAMs for RPV is low except for E138A (present in 5.1% of subjects). The combination E138K?+?M184I is absent in both naïve and experienced subjects. A previous exposure to NVP might increase the risk to develop RPV-associated RAMs. TDF, EFV, and possibly FTC may predispose to the selection for M184I. Among Italian patients the susceptibility to RPV is widespread since some severe substitutions (e.g., E138K are rare), whereas issues exist for others (i.e., E138A, Y181C) which are more frequent. Appropriate use of RPV within a therapeutic sequencing might be controversial. J. Med. Virol. 86:1459-1466, 2014. © 2014 Wiley Periodicals, Inc. PMID:24838991

Rossotti, Roberto; Fonte, Luigi; Meini, Genny; Maggiolo, Franco; Zazzi, Maurizio; Rusconi, Stefano

2014-09-01

174

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

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.

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

2013-01-01

175

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

PubMed Central

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

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

2014-01-01

176

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

PubMed

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

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

2013-03-01

177

Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines  

Microsoft Academic Search

Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676, has recently been introduced to clinics as a promising drug to treat patients with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60, NOMO-1, NB4, NKM-1, K562, Daudi, and the multidrug-resistant sublines, NOMO-1\\/ADR and NB4\\/MDR, was investigated

K Naito; A Takeshita; K Shigeno; S Nakamura; S Fujisawa; K Shinjo; H Yoshida; K Ohnishi; M Mori; S Terakawa; R Ohno

2000-01-01

178

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

PubMed Central

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.

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

2012-01-01

179

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

PubMed

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

Sikora, Agnieszka; Kozio?-Montewka, Maria; Bogut, Agnieszka

2011-01-01

180

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

ERIC Educational Resources Information Center

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…

Silva, Roberta K.

181

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

PubMed Central

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

2013-01-01

182

Drug Addiction  

PubMed Central

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.

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

2011-01-01

183

"Jingo Lida et. al. 2011 formulated pulsatile drug delivery system based on an impermeable copiously. A pulsatile copiously was prepared by sealing a 5-aminosalicylic acid rapid-disintegrating tablet inside an impermeable copiously body with a konjac glucomannan (Kam)?hydroxypropyl methylcellulose (HPC)?locates plug. The drug delivery system showed a typical pulsatile release profile with a lag time followed by a rapid release phase. The lag time was determined by the Kam"  

EPA Pesticide Factsheets

Did you mean: "Jingo Lida et. al. 2011 formulated pulsatile drug delivery system based on an impermeable copiously. A pulsatile copiously was prepared by sealing a 5-aminosalicylic acid rapid-disintegrating tablet inside an impermeable copiously body with a konjac glucomannan (Kam)?hydroxypropyl methylcellulose (HPC)?locates plug. The drug delivery system showed a typical pulsatile release profile with a lag time followed by a rapid release phase. The lag time was determined by the Kam" ?

184

Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [ 123 I]?-CIT SPECT  

Microsoft Academic Search

Ten healthy subjects and 16 patients with early Parkinson’s disease (PD) were examined with single photon emission computed\\u000a tomography (SPECT) and [123I]?-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding\\u000a to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [123I]?-CIT binding in

G. Tissingh; P. Bergmans; J. Booij; A. Winogrodzka; E. A. van Royen; J. C. Stoof; E. C. Wolters

1997-01-01

185

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

PubMed

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

Durden, David A

2007-05-01

186

Testosterone gel shows promise in Phase III trial.  

PubMed

Early results from a Phase III trial of Androgel, a testosterone replacement gel developed by Unimed Pharmaceuticals, shows that it effectively restores testosterone serum levels without skin irritation. The transdermal delivery has been found to adequately replace the hormone, and is easy to apply. The study did not target AIDS patients, but other studies have shown that testosterone-replacement therapy is effective in regaining muscle mass and improving the physical and mental state of HIV-positive patients. The drug will be sold in doses of 25 mg-dose packages, and clinicians will be able to prescribe two- or four-package doses as appropriate. Europeans have administered androgens in a gel form for over 15 years, but this is the first time such a product will be available in the United States. Unimed plans to submit the drug for Food and Drug Administration (FDA) approval soon. PMID:11366410

1999-06-01

187

Television Quiz Show Simulation  

ERIC Educational Resources Information Center

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.

Hill, Jonnie Lynn

2007-01-01

188

Positive Proof.  

ERIC Educational Resources Information Center

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

Auty, Geoffrey

1988-01-01

189

Homemade Laser Show  

NSDL National Science Digital Library

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

Houston, Children'S M.

2011-01-01

190

A Holographic Road Show.  

ERIC Educational Resources Information Center

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)

Kirkpatrick, Larry D.; Rugheimer, Mac

1979-01-01

191

Trade Show Managers  

Microsoft Academic Search

Trade show management is a multi-faceted field, requiring a breadth of skills on the part of those engaged in the craft. Whether they go by the title of Show Manager, Director of Marketing, Vice President of Meetings\\/Conventions, or Director of Meetings\\/Conventions, these professionals work with exhibitors, attendees, and service providers to produce their events. The managers of the 200 largest

Susan Gregory; Deborah Breiter

2001-01-01

192

Demonstration Road Show  

NSDL National Science Digital Library

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

Shropshire, Steven

2009-04-06

193

Showing What They Know  

ERIC Educational Resources Information Center

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

Cech, Scott J.

2008-01-01

194

The Ozone Show.  

ERIC Educational Resources Information Center

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

Mathieu, Aaron

2000-01-01

195

Blue Ribbon Art Show.  

ERIC Educational Resources Information Center

Describes the process of selecting judges for a Blue Ribbon Art Show (Springfield, Missouri). Used adults (teachers, custodians, professional artists, parents, and principals) chosen by the Willard South Elementary School art teacher to judge student artwork. States that nominated students received blue ribbons. (CMK)

Bowen, Judy Domeny

2002-01-01

196

Fluency of Pharmaceutical Drug Names Predicts Perceived Hazardousness, Assumed Side Effects, and Willingness to Buy.  

PubMed

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

Dohle, Simone; Siegrist, Michael

2013-06-01

197

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

PubMed Central

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

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

2012-01-01

198

Show-Me Center  

NSDL National Science Digital Library

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

199

The Graphing Game Show  

NSDL National Science Digital Library

This lesson plan assesses student interpretation of graphs utilizing cooperative learning to further students understanding. Types of graphs used are horizontal and vertical bar graphs, picture graphs, and pictographs. In the lesson students play a game called the Graphing Game Show, in which they must work as a team to answer questions about specific graphs. The lesson includes four student resource worksheets and suggestions for extension and differentiation.

2011-01-01

200

Education Statistics Slide Show  

NSDL National Science Digital Library

Created by Grace York, coordinator of the University of Michigan's Documents Center, the Education Statistics Slide Show is an online presentation demonstrating how to locate, obtain, and manipulate educational data on the Web. The presentation consists of 72 slides and offers instruction on the use of several Websites including the US Census Bureau's American Factfinder site (see the April 2, 1999 Scout Report), the Center for International Earth Science Information Network (CIESIN) Census Mapping site, the National Center for Education Statistics (NCES) site, the FEDSTATS site (see the May 30, 1997 Scout Report), and many more. The tutorial presentation also provides ten practice questions and a detailed Webliography.

201

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

PubMed

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

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

2013-11-01

202

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

PubMed

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

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

2014-07-01

203

Show-Me Center  

NSDL National Science Digital Library

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

204

The Role of Cavitation in Acoustically Activated Drug Delivery  

PubMed Central

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

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

2006-01-01

205

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

PubMed Central

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

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

2014-01-01

206

UCSF Cancer Center Research Shows Promise of New Drugs  

Cancer.gov

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

207

Anti-Alzheimer's Drug Shows Promise in Mice Study  

MedlinePLUS

... In the study, the compound cut levels of amyloid beta -- a protein associated with this degenerative brain disease -- ... half, the researchers said. Years before Alzheimer's develops, amyloid beta starts to build up and clump in the ...

208

Positive Lives  

NSDL National Science Digital Library

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

209

Drugged Driving  

MedlinePLUS

... the Military Treatment Approaches for Drug Addiction NIDA Publications By Audience By Drug of Abuse By Drug ... Milestone: One Week of Transdermal Drug Delivery Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ...

210

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

PubMed Central

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

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

1992-01-01

211

Nasal carriage of multi-drug resistant Panton-Valentine leucocidin-positive methicillin-resistant Staphylococcus aureus in children in Tripoli-Libya.  

PubMed

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

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

2014-04-01

212

Drug Usage and Attitude Toward Drugs Among College Students  

ERIC Educational Resources Information Center

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

Cross, Herbert J.; Keir, Richard G.

1971-01-01

213

Drug allergies  

MedlinePLUS

Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... vomiting to life-threatening anaphylaxis . A true drug allergy is caused by a series of chemical steps ...

214

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

PubMed Central

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

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

2014-01-01

215

Drugs and Drug Abuse.  

ERIC Educational Resources Information Center

GRADES OR AGES: Secondary grades. SUBJECT MATTER: Drugs and drug abuse. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into several sections, each of which is in outline or list form. It is xeroxed and spiral-bound with a paper cover. OBJECTIVES AND ACTIVITIES: No objectives are mentioned. The major portion of the guide contains a…

Anastas, Robert, Comp.; And Others.

216

Avoiding Drug-Drug Interactions  

Microsoft Academic Search

Background: Drugs may be prescribed in combinations causing drug-drug interactions (DDI) and adverse drug reactions (ADR), resulting in hospital care. Methods: To provide prescribers of drug therapy with a better knowledge of individuals’ current drug therapy, governments have started to collect prescribing data. Results: The data on individuals’ dispensed drugs is available for prescribers, pharmacists, and the registered individuals in

Bengt Åstrand

2009-01-01

217

Drugs and their interactions.  

PubMed

Small molecules with selective efficacy can be used as drugs. Drugs typically have a therapeutic dose range where the benefit from intended effects outweighs the cost of unintended (side) effects. Herein, I use case scenarios to illustrate potential advantages and pitfalls of treatment with drugs alone or in combination. Combinations of drugs may show surprising effects given the effects of individual drugs, in phenomena known as drug interactions. Drug interactions can be classified as synergistic or antagonistic, if the effect of the combination is higher or lower than expected, respectively. A better understanding of drug interactions and their relationship to phenotypes offers hope in finding drug combinations that have high therapeutic values. PMID:23237673

Cokol, Murat

2013-06-01

218

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

PubMed

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

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

2000-02-01

219

Clearinghouse: women and drugs.  

PubMed

Thirteen references to treatment centers for HIV-positive, drug-dependent women are provided. Contact numbers for medical professionals and additional information for various states, including Illinois, California, Maryland, and New York, are listed. PMID:11363032

1995-09-01

220

Generic antiepileptic drugs  

Microsoft Academic Search

Opinion statement  Generic antiepileptic drugs (AEDs) generally provide safe, effective, lower-cost alternatives to brand-name drugs. To be approved\\u000a by the US Food and Drug Administration (FDA), manufacturers must show that generic drugs are comparable to brand-name formulations,\\u000a meeting bioequivalence, dissolution, and manufacturing quality standards. Bioequivalence for most generic formulations is\\u000a evaluated by measuring blood pharmacokinetic values in a small, crossover study

Susan J. Shaw; Gregory L. Krauss

2008-01-01

221

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

PubMed Central

Hepatitis C virus (HCV) is hyperendemic among injection drug users (IDUs). However, few scientifically proven interventions to prevent secondary transmission of HCV from infected IDUs to others exist. This report describes the design, feasibility, and baseline characteristics of participants enrolled in the Study to Reduce Intravenous Exposure (STRIVE). STRIVE was a multisite, randomized-control trial to test a behavioral intervention developed to reduce distribution of used injection equipment (needles, cookers, cottons, and rinse water) and increase health-care utilization among antibody HCV (anti-HCV) positive IDUs. STRIVE enrolled anti-HCV positive IDU in Baltimore, New York City, and Seattle; participants completed behavioral assessments and venipuncture for HIV, HCV-RNA, and liver function tests (LFTs) and were randomized to attend either a six-session, small-group, peer-mentoring intervention workshop or a time-matched, attention-control condition. Follow-up visits were conducted at 3 and 6 months. At baseline, of the 630 HCV-positive IDUs enrolled (mean age of 26 years, 60% white, 76% male), 55% reported distributive needle sharing, whereas 74, 69, and 69% reported sharing cookers, cottons, and rinse water, respectively. Health-care access was low, with 41% reporting an emergency room as their main source of medical care. Among those enrolled, 66% (418/630) were randomized: 53% (222/418) and 47% (196/418) to the intervention and control conditions, respectively. Follow-up rates were 70 and 73% for the 3- and 6-month visits, respectively. As distributive sharing of used injection equipment was common while reports of receiving HCV care were low, these findings indicate an urgent need for HCV-related interventions with IDUs and demonstrate the acceptability and feasibility to do so.

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

2007-01-01

222

Possible markers for postmortem drug redistribution.  

PubMed

The possibility that postmortem biochemical changes in blood might parallel drug redistribution and thus serve as markers was explored in a detailed case study. Eighteen blood and 14 tissue and fluid samples were taken at autopsy 16 h after the death of a 34-year-old female from amitriptyline overdose. Ranges of drug concentrations in blood were amitriptyline 1.8 to 20.2 micrograms/mL, nortriptyline 0.6 to 7.3 micrograms/mL, levels were lowest in femoral vein and highest in pulmonary vein blood. Corresponding levels of 17 amino acids showed markedly different patterns of site-to-site variability. There was a strong positive correlation between individual amino acid and drug concentrations in pulmonary blood samples (n = 5), particularly for glycine, leucine, methionine, serine, and valine. In blood samples from the great veins and right heart (n = 10), the correlation was less strong (r = 0.6 to 0.7). Methionine showed a strong positive correlation in pulmonary samples (r = 0.93), and negative correlation in great veing samples (r = -0.68). Lactic acid showed a strong negative correlation in pulmonary samples (r = -0.93) but a positive correlation in great vein samples (r = 0.71). Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, and bilirubin had a weak positive correlation with drug levels in great vein samples but not pulmonary samples. The results suggest that hepatic enzymes are relatively poor markers for postmortem hepatic drug shifts but that amino acids, particularly methionine, may be useful markers for pulmonary drug shifts. PMID:8988578

Langford, A M; Pounder, D J

1997-01-01

223

Peripheral lymphocyte culture in the diagnosis of drug induced liver injury  

Microsoft Academic Search

Summary  In order to evaluate the usefulness of the peripherl lymphocyte culture method for the diagnosis of drug-induced liver injury,\\u000a a study was carried out on 21 cases of drug-induced liver injury (Group A). Nine cases in Group A showed a positive lymphocyte\\u000a stimulation test. Out of 9 cases which showed positive stimulation six cases were cholestatic type of liver injury,

Yasuhiro Kato; Kenichi Kobayashi; Nobu Hattori; Jugoro Takeuchi; Goroku Ota

1979-01-01

224

Scaring Kids' Shows Off TV.  

ERIC Educational Resources Information Center

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

Raspberry, William

1980-01-01

225

The drug cocktail network  

PubMed Central

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

2012-01-01

226

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

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.

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

2012-01-01

227

Antitumor drugs as photochemotherapeutic agents  

NASA Astrophysics Data System (ADS)

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

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

1991-11-01

228

Prescription Drugs  

MedlinePLUS

... Prescription Drug Abuse in Youth (August 2013) Featured Publications Cough and Cold Medicine Abuse (DrugFacts) Revised May ... Treatment Locator or 1-800-662-HELP . Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ...

229

Drug Abuse.  

National Technical Information Service (NTIS)

Drugs are defined as chemical substances which either stimulate or depress the central nervous system. The categories of drugs described are stimulants, hallucinogenic drugs and amphetamines and depressants (tranquilizers, barbiturates, and opiates). The ...

1994-01-01

230

Micellar nanoparticles loaded with gemcitabine and doxorubicin showed synergistic effect.  

PubMed

Gemcitabine and doxorubicin were separately chemically linked to biodegradable polymers to prepare polymer-gemcitabine and polymer-doxorubicin conjugates. Moreover, the two conjugates can self-assemble into micelles with both gemcitabine and doxorubicin. In this way, the two anticancer drugs were combined. The in vitro MTT assay with these combined drugs showed synergistic effect compared to single use of each drug. PMID:24077114

Liu, Dechun; Chen, Yanbin; Feng, Xiaoshan; Deng, Miao; Xie, Gangqiang; Wang, Jianguang; Zhang, Like; Liu, Qipeng; Yuan, Pengfei

2014-01-01

231

Drug abuse profile - patient delay, diagnosis delay and drug resistance pattern - among addict patients with tuberculosis.  

PubMed

Socioeconomic problems limit the access of drug users to health-care services. This descriptive cross-sectional study was carried out by making use of the medical records of new case tuberculosis (TB) patients hospitalized at Masih Daneshvari Hospital, the national referral centre in Iran, from 2003 to 2006. Demographic and personal characteristics of the patients and type of disease were collected and categorized. Of the 944 patients with confirmed TB, 143 (15.1%) were drug users, among whom 140 (97.9%) were men with just three women drug users. The mean age of the drug users group was 43.04 +/- 13.81 years. The type of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and heroin together in four (2.8%) and all three, opium, heroin and crack, in two (1.4%). For 238 high-risk patients, an HIV test was performed and HIV infection was confirmed in 33 cases. Patient delay was longer in drug users (P = 0.000) against other patients, whereas diagnosis delay was shorter (P = 0.007). Drug susceptibility tests were performed for 515 patients with positive cultures. One hundred and thirty-three (14.1%) were found to have 'any resistance' to anti-TB drugs, and 10 (1.1%) individuals had multidrug-resistant TB. Twenty-six (19.5%) of the individuals who showed resistance to first-line agents were drug users. There was no significant relation between drug resistance and drug use (P = 0.4). In conclusion, it seems that active case finding for TB and HIV in addict cases must be contained in harm reduction packages. Moreover, the manifestations of the disease should be considered seriously regardless of attributing them to drug use. PMID:19386968

Shamaei, M; Marjani, M; Baghaei, P; Chitsaz, E; Rezaei Tabar, E; Abrishami, Z; Tabarsi, P; Mansouri, D; Masjedi, M R

2009-05-01

232

Legalization of drugs of abuse and the pediatrician.  

PubMed

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. PMID:1928008

Schwartz, R H

1991-10-01

233

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 — ...

234

Asia: Showing the Changing Seasons  

NSDL National Science Digital Library

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

Allen, Jesse; Newcombe, Marte; Feldman, Gene

1998-09-09

235

What Do Blood Tests Show?  

MedlinePLUS

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

236

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

Federal Register 2010, 2011, 2012, 2013

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

2011-04-01

237

Rings in drugs.  

PubMed

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

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

2014-07-24

238

Positional plagiocephaly  

PubMed Central

Cranial asymmetry occurring as a result of forces that deform skull shape in the supine position is known as deformational plagiocephaly. The risk of plagiocephaly may be modified by positioning the baby on alternate days with the head to the right or the left side, and by increasing time spent in the prone position during awake periods. When deformational plagiocephaly is already present, physiotherapy (including positioning equivalent to the preventive positioning, and exercises as needed for torticollis and positional preference) has been shown to be superior to counselling about preventive positioning only. Helmet therapy (moulding therapy) to reduce skull asymmetry has some drawbacks: it is expensive, significantly inconvenient due to the long hours of use per day and associated with skin complications. There is evidence that helmet therapy may increase the initial rate of improvement of asymmetry, but there is no evidence that it improves the final outcome for patients with moderate or severe plagiocephaly.

Cummings, Carl

2011-01-01

239

Planning a Successful Tech Show  

ERIC Educational Resources Information Center

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

Nikirk, Martin

2011-01-01

240

Drug and Alcohol Involvement in Four Types of Fatal Crashes*  

PubMed Central

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.

Romano, Eduardo; Voas, Robert B.

2011-01-01

241

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

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…

American Association of School Administrators, Arlington, VA.

242

Club drug use among college students  

Microsoft Academic Search

This study examined prevalence and frequency of “club” drug use among college students (N=831) and associations with marijuana and alcohol use, sensation seeking, and positive and negative affectivity. Eighteen percent (n=146) of the sample had used club drugs at least once in their lifetime. Results of a logistic regression indicated that club drug use was positively associated with marijuana use,

Jeffrey S. Simons; Raluca M. Gaher; Christopher J. Correia; Jacqueline A. Bush

2005-01-01

243

Comparisons show construction management's benefits.  

PubMed

Analysis of competitive bid, design-build, and construction management approaches shows that construction management offers owners substantial advantages regarding project cost and quality and substantial involvement and control throughout the process. PMID:110667

Payette, T M

1979-09-01

244

Using Graphs to Show Connections  

NSDL National Science Digital Library

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

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

2003-08-01

245

Drug-drug interaction through molecular structure similarity analysis  

PubMed Central

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

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

2012-01-01

246

Club Drugs  

MedlinePLUS

... from the previous year. Previous MTF Data Featured Publications Methamphetamine (DrugFacts) Published March 2010 . Revised January 2014 . ... Treatment Locator or 1-800-662-HELP . Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ...

247

Drug Control  

ERIC Educational Resources Information Center

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

Leviton, Harvey S.

1975-01-01

248

Drug Paraphernalia  

MedlinePLUS

... to conceal drugs include: Plastic baggies or small paper bags Cigarette packages Small glass vials Pill bottles ... be used with the specific drug. Marijuana Rolling papers Cigars used to fill with marijuana to make ...

249

Nuclear Positioning  

PubMed Central

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

Gundersen, Gregg G.; Worman, Howard J.

2013-01-01

250

The OOPSLA trivia show (TOOTS)  

Microsoft Academic Search

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

Jeff Gray; Douglas C. Schmidt

2009-01-01

251

Homelessness and drug misuse in developing countries: A mathematical approach  

NASA Astrophysics Data System (ADS)

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

Bhunu, C. P.

2014-06-01

252

Positive Computing  

Microsoft Academic Search

\\u000a In his opening speech at the International Positive Psychology Association (IPPA) Conference in June 2009, Martin Seligman,\\u000a founder of Positive Psychology, formulated a formidable challenge: By the year 2051, 51% of the world population should be\\u000a flourishing. This is an ambitious goal given that even in the richer, “happier” Western world only 2 in 10 people are considered\\u000a to be

Tomas Sander

253

Who Tests which Athletes for What Drugs?  

ERIC Educational Resources Information Center

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

Gall, Sarah L.; And Others

1988-01-01

254

Peptoid analogues of anoplin show antibacterial activity.  

PubMed

We have synthesised nine analogues of the antibacterial peptide anoplin with a peptoid residue at position 5 (H-GLLKXIKTLL-NH(2)). The most active compounds showed MIC-values of 12.5 and 25 microM against E.coli and S.aureus. These MIC-values are comparable with anoplin which showed 23 microM and 11 microM against E. coli and S.aureus. However, the selectivity was reversed. Our results indicate that peptoid analogues of anoplin are promising lead structures for developing new antibacterial agents. PMID:19799550

Meinike, K; Hansen, P R

2009-01-01

255

Drug Interactions  

PubMed Central

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

Tong Logan, Angela; Silverman, Andrew

2012-01-01

256

Patents Associated with High-Cost Drugs in Australia  

PubMed Central

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

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

2013-01-01

257

Pseudoephedrine may cause "pigmenting" fixed drug eruption.  

PubMed

Fixed drug eruption (FDE) is a distinctive drug eruption characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. Two different clinical forms have been described: the common classic pigmenting form and the rare nonpigmenting form. Nonpigmenting FDE is mainly characterized by symmetrical large erythematous plaques and the dermal histopathologic reaction pattern. Pseudoephedrine is known as the major inducer of nonpigmenting FDE. Pigmenting FDE from pseudoephedrine has not been reported previously. Here, the first case of pseudoephedrine-induced pigmenting FDE is reported, showing the characteristic features of classic pigmenting FDE such as asymmetry, normal-sized lesions, and the epidermodermal histopathologic reaction pattern. Moreover, a positive occlusive patch-test reaction to pseudoephedrine could be demonstrated on postlesional FDE skin for the first time. PMID:21569741

Ozkaya, Esen; Elinç-Aslan, Meryem Sevinç

2011-05-01

258

Drug metabolism and drug toxicity  

Microsoft Academic Search

Adverse drug reactions are a major problem for both health care providers and the pharmaceutical industry. They are a common and significant cause of morbidity and mortality and occasionally result in the withdrawal of an otherwise valuable therapeutic agent. There is now overwhelming evidence that adverse drug reactions are often caused by a metabolite of the drug rather than the

B. Kevin Park; Neil R. Kitteringham; Jane R. Kenny; Munir Pirmohamed

2001-01-01

259

The Drug Development Process II: Investigational New Drug Application  

Microsoft Academic Search

he development of a new drug requires strict adherence to the Code of Federal Regulations, starting with the application for study of the compound in human subjects. Prior to a drug's entry into the clinic, pharmaceutical companies (here- after referred to as sponsors) must test the drug candi- date in specific ways in order to show with reasonable certainty that

Bertrand C. Liang

260

Position indicator  

DOEpatents

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

Tanner, David E. (Poway, CA)

1981-01-01

261

GWAS and drug targets  

PubMed Central

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

2014-01-01

262

When Oprah Intervenes: Political Correlates of Daytime Talk Show Viewing  

Microsoft Academic Search

This study examined the influence of daytime talk shows on opinion formation. Using agenda-setting and cultivation perspectives, it was hypothesized that both exposure to daytime talk shows and the apparent reality of these shows would be positively related to support for government involvement in social issues. In addition to exposure and apparent reality being positively related to levels of support,

Carroll J. Glynn; Michael Huge; Jason B. Reineke; Bruce W. Hardy; James Shanahan

2007-01-01

263

Casimir experiments showing saturation effects  

NASA Astrophysics Data System (ADS)

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 ; 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 ; 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 of the change in oscillation frequency of a R87b Bose-Einstein condensate trapped to a fused silica wall; the change is smaller than predicted by theory. We show that saturation effects can explain the discrepancies between theory and experiment observed in all these cases.

Sernelius, Bo E.

2009-10-01

264

Casimir experiments showing saturation effects  

SciTech Connect

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

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

2009-10-15

265

A Promising Cross-Border HIV Prevention Project for Injection Drug Users In provinces of southern China and northern Vietnam one of the first HIV prevention projects operating across an international border shows progress in stemming the growth of the HIV\\/AIDS epidemic and provides lessons to the international community  

Microsoft Academic Search

major heroin trans-shipment route runs from the producing region in the Golden Triangle of Thailand, Myanmar, and Laos into northern Vietnam and southern China, and on to Hong Kong, a gateway to the larger world. Over time, as the drug became increasingly available to local populations along this route, traditional opium smoking gave way to heroin inhalation and then injection.

T. Hammett

2005-01-01

266

Alcohol, Drugs and Young Drivers.  

ERIC Educational Resources Information Center

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

Voas, Robert B.

267

Speaking Out against Drug Legalization.  

National Technical Information Service (NTIS)

Members of law enforcement, educational, prevention, and social service communities are frequently faced with the need to address many of the positions which are advocated by those calling for the legalization of drugs. More and more, the debate on legali...

2000-01-01

268

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

Microsoft Academic Search

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

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

2005-01-01

269

Mimas Showing False Colors #1  

NASA Technical Reports Server (NTRS)

False color images of Saturn's moon, Mimas, reveal variation in either the composition or texture across its surface.

During its approach to Mimas on Aug. 2, 2005, the Cassini spacecraft narrow-angle camera obtained multi-spectral views of the moon from a range of 228,000 kilometers (142,500 miles).

The image at the left is a narrow angle clear-filter image, which was separately processed to enhance the contrast in brightness and sharpness of visible features. The image at the right is a color composite of narrow-angle ultraviolet, green, infrared and clear filter images, which have been specially processed to accentuate subtle changes in the spectral properties of Mimas' surface materials. To create this view, three color images (ultraviolet, green and infrared) were combined into a single black and white picture that isolates and maps regional color differences. This 'color map' was then superimposed over the clear-filter image at the left.

The combination of color map and brightness image shows how the color differences across the Mimas surface materials are tied to geological features. Shades of blue and violet in the image at the right are used to identify surface materials that are bluer in color and have a weaker infrared brightness than average Mimas materials, which are represented by green.

Herschel crater, a 140-kilometer-wide (88-mile) impact feature with a prominent central peak, is visible in the upper right of each image. The unusual bluer materials are seen to broadly surround Herschel crater. However, the bluer material is not uniformly distributed in and around the crater. Instead, it appears to be concentrated on the outside of the crater and more to the west than to the north or south. The origin of the color differences is not yet understood. It may represent ejecta material that was excavated from inside Mimas when the Herschel impact occurred. The bluer color of these materials may be caused by subtle differences in the surface composition or the sizes of grains making up the icy soil.

The images were obtained when the Cassini spacecraft was above 25 degrees south, 134 degrees west latitude and longitude. The Sun-Mimas-spacecraft angle was 45 degrees and north is at the top.

The Cassini-Huygens mission is a cooperative project of NASA, the European Space Agency and the Italian Space Agency. The Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the mission for NASA's Science Mission Directorate, Washington, D.C. The Cassini orbiter and its two onboard cameras were designed, developed and assembled at JPL. The imaging operations center is based at the Space Science Institute in Boulder, Colo.

For more information about the Cassini-Huygens mission visit http://saturn.jpl.nasa.gov . The Cassini imaging team homepage is at http://ciclops.org .

2005-01-01

270

Voice of the psychonauts: coping, life purpose, and spirituality in psychedelic drug users.  

PubMed

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

Móró, Levente; Simon, Katalin; Bárd, Imre; Rácz, József

2011-01-01

271

Positive Psychologists on Positive Constructs  

ERIC Educational Resources Information Center

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…

Lyubomirsky, Sonja

2012-01-01

272

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

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…

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

2007-01-01

273

Fast-dissolving microparticles fail to show improved oral bioavailability.  

PubMed

Oral dosage forms are the preferred means of delivering drugs for systemic absorption. However, development problems occur for drugs with poor water solubility and/or gastrointestinal permeability. It is generally believed that the in-vivo bioavailability of poorly water-soluble drugs from Class II of the Biopharmaceutics Classification System can be improved by increasing the dissolution rate. We have attempted to increase the in-vivo oral bioavailability of a model Class II drug (griseofulvin) by preparing rapidly-dissolving particles. The solvent-diffusion method was used to prepare particles with hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies were conducted in rats. The griseofulvin particles produced were bipyramidal in habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The latter and the small particle size ensured rapid particle dispersion and dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the bipyramidal particles had released approximately 70% of drug compared with approximately 10% from the starting material (particle size 12.61 +/- 1.11 microm). However, the rapid and increased drug dissolution in-vitro was not translated to rapid and enhanced absorption in-vivo, and the oral bioavailability of the model drug was found to be the same from the control and from the bipyramidal particles. The poor in-vivo performance of the bipyramidal particles showed that although the dissolution rate of a Class II drug is thought to be a good indicator of its in-vivo bioavailability, this is not always the case. PMID:17034654

Wong, S M; Kellaway, I W; Murdan, S

2006-10-01

274

Probabilistic drug connectivity mapping  

PubMed Central

Background The aim of connectivity mapping is to match drugs using drug-treatment gene expression profiles from multiple cell lines. This can be viewed as an information retrieval task, with the goal of finding the most relevant profiles for a given query drug. We infer the relevance for retrieval by data-driven probabilistic modeling of the drug responses, resulting in probabilistic connectivity mapping, and further consider the available cell lines as different data sources. We use a special type of probabilistic model to separate what is shared and specific between the sources, in contrast to earlier connectivity mapping methods that have intentionally aggregated all available data, neglecting information about the differences between the cell lines. Results We show that the probabilistic multi-source connectivity mapping method is superior to alternatives in finding functionally and chemically similar drugs from the Connectivity Map data set. We also demonstrate that an extension of the method is capable of retrieving combinations of drugs that match different relevant parts of the query drug response profile. Conclusions The probabilistic modeling-based connectivity mapping method provides a promising alternative to earlier methods. Principled integration of data from different cell lines helps to identify relevant responses for specific drug repositioning applications.

2014-01-01

275

Interoception and drug addiction.  

PubMed

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. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. PMID:23855999

Paulus, Martin P; Stewart, Jennifer L

2014-01-01

276

Antithyroid Drugs  

Microsoft Academic Search

The management of the antithyroid drug therapy is inferred from the preceding papers. The best duration for the treatment with antithyroid drugs (ATD) is 18 months. At the end of the treatment, the early radioiodine uptake measured on suppressive doses of LT3 and the determination of the thyroid-stimulating antibodies are the only two interesting parameteres in order to predict the

Jacques Leclère

1987-01-01

277

Drug Education.  

ERIC Educational Resources Information Center

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

Sardana, Raj K.

278

Antigiardial drugs  

Microsoft Academic Search

Giardia intestinalis is a world-wide cause of intestinal infection. Treatment of this debilitating disease is usually accomplished using one of several drugs. Metronidazole is the treatment of choice, but benzimidazoles are now being used more frequently. Other treatments include quinacrine, paromomycin and furazolidone. Even though these drugs are all used to treat the same disease, their modes of action differ

J. Harris; S. Plummer; D. Lloyd

2001-01-01

279

Therapeutic drug monitoring: chemical-clinical correlations of atypical antipsychotic drugs.  

PubMed

In the last few years, new drugs for the treatment of schizophrenia have been introduced in therapy which have noticeably improved the quality of life of many schizophrenic patients. These new "atypical" drugs have chemical, pharmacological and clinical properties which are different from those of the classical neuroleptics. The most used drugs among the "atypical" antipsychotics are clozapine, olanzapine, quetiapine and risperidone. Despite several differences in their pharmacokinetic and pharmacodynamic profiles, they show some common properties: e.g. they don't cause extrapyramidal side effects, and they are active against the negative as well as positive symptoms of schizophrenia. The need for clinical monitoring of patients undergoing therapy is still evident because the onset of side effects is often related to high plasma concentrations of the drug. The clinical monitoring of patients can significantly improve the knowledge of pharmacological interactions among different CNS drugs, as well as enhance the compliance of the patients, thus leading to higher treatment efficacy. In order to carry out efficient clinical monitoring, reliable analytical methods are needed to determine the analytes even at very low concentrations and in the presence of other drugs. For this purpose, analytical techniques such as gas or liquid chromatography are often used coupled with sensitive and selective means of detection, such as fluorimetric, electrochemical or mass spectrometry detectors. The most recent studies on the determination of atypical antipsychotics will be reviewed in addition to the issue of sample pretreatment which is a critical step when the analysis of biological fluids is concerned. PMID:12143799

Raggi, M A

2002-07-01

280

66 FR 14454 - Certification for Major Illicit Drug Producing and Drug  

Federal Register 2010, 2011, 2012, 2013

...begun in 1999, inspected 398 aircraft in 2000, finding 58 violations with 20 testing positive for drug residue. The aerial eradication...and well- developed financial services sector make it a crossroads for transnational crime, such as drug trafficking,...

2001-03-12

281

3 CFR - Certification for Major Illicit Drug Producing and Drug Transit Countries  

Code of Federal Regulations, 2010 CFR

...begun in 1999, inspected 398 aircraft in 2000, finding 58 violations with 20 testing positive for drug residue. The aerial...and well-developed financial services sector make it a crossroads for transnational crime, such as drug trafficking,...

2002-01-01

282

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

PubMed

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

Jacobson-Kram, David; Jacobs, Abigail

2005-01-01

283

Positioning apparatus  

DOEpatents

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

Vogel, M.A.; Alter, P.

1983-07-07

284

Positioning apparatus  

DOEpatents

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

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

1986-01-01

285

Evaluation of drug interactions with nanofibrillar cellulose.  

PubMed

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

Kolakovic, Ruzica; Peltonen, Leena; Laukkanen, Antti; Hellman, Maarit; Laaksonen, Päivi; Linder, Markus B; Hirvonen, Jouni; Laaksonen, Timo

2013-11-01

286

In vitro validation of drug-induced phospholipidosis.  

PubMed

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

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

2012-01-01

287

Cyclodextrins in nasal drug delivery.  

PubMed

Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large size and hydrophilicity, resulting in poor transport properties across the nasal mucosa. Cyclodextrins are used to improve the nasal absorption of these drugs by increasing their aqueous solubility and/or by enhancing their nasal absorption. With several cyclodextrins very efficient nasal drug absorption has been reported, but also large interspecies differences have been found. Studies concerning the safety of cyclodextrins in nasal drug formulations demonstrate the non-toxicity of the cyclodextrins and also clinical data show no adverse effects. Therefore, some cyclodextrins can be expected to become effective and safe excipients in nasal drug delivery. PMID:10837708

Merkus; Verhoef; Marttin; Romeijn; van der Kuy PH; Hermens; Schipper

1999-03-01

288

GENDER-RESPONSIVE DRUG COURT TREATMENT  

PubMed Central

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

Messina, Nena; Calhoun, Stacy; Warda, Umme

2014-01-01

289

[Club drugs].  

PubMed

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

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

2011-01-01

290

Ligand-exchangeability of 2-coordinate phosphinegold(I) complexes with AuSP and AuNP cores showing selective antimicrobial activities against Gram-positive bacteria. Crystal structures of [Au(2-Hmpa)(PPh 3)] and [Au(6-Hmna)(PPh 3)] (2-H 2mpa=2-mercaptopropionic acid, 6-H 2mna=6-mercaptonicotinic acid)  

Microsoft Academic Search

Selective and effective antimicrobial activities against Gram-positive bacteria (B. subtilis and\\/or S. aureus) were found in 2-coordinate gold(I)–PPh3 complexes with AuSP and AuNP cores, i.e. [Au(L)(PPh3)] (HL=2-H2mna [H2mna=mercaptonicotinic acid] 3, d-H2pen [H2pen=penicillamine] 4, d,l-H2pen 5, 4-H2mba [H2mba=mercaptobenzoic acid] 8, Hpz [Hpz=pyrazole] 9, Him [Him=imidazole] 10, 1,2,3-Htriz [Htriz=triazole] 11, 1,2,4-Htriz 12, Htetz [Htetz=tetrazole] 13), whereas no activity was observed in 2-coordinate

Kenji Nomiya; Satoshi Yamamoto; Ryusuke Noguchi; Hironari Yokoyama; Noriko Chikaraishi Kasuga; Kei Ohyama; Chieko Kato

2003-01-01

291

A Developmental Perspective on Adolescent Drug Abuse  

Microsoft Academic Search

Adolescent drug use is placed in an historical and developmental perspective. Existing evidence concerning causes and consequences of adolescent drug use is inconclusive. In the absence of conclusive empirical evidence and cogent theories, we present a prima facie case against early adolescent drug use by defending six propositions which posit specific cognitive, conative, and affective negative consequences including impairment of

Diana Baumrind; Kenneth A. Moselle

1985-01-01

292

[Antihypertensive drug-drug interactions].  

PubMed

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37 and 60% of hospital-admissions are treated with potentially dangerous drug associations and up to a 6% of fatal events are due to this circumstance. Among antihypertensive drugs, diuretics and angiotensin converting enzyme inhibitors are less affected by drug-interactions. Lipophilic beta-blockers agents may present some clinical relevant interactions, whereas calcium channel blockers, especially the non-dihydropiridinic ones, are implied in clinically relevant pharmacokinetic interactions. Among the angiotensin receptor blockers there are differences that would have to be considered when they are used in patients who receive other drugs. Although it is impossible for the doctor to remember all the clinical relevant interactions, it is important to bear in mind their existence and the possible mechanisms of production which can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein. Enzymes of the cytochrome P450 system may present polymorphisms that can explain the individual differences in the response to drugs or the appearance of drug-interactions. PMID:15927106

Morales-Olivas, Francisco J; Estañ, Luis

2005-05-28

293

Tunable drug loading and release from polypeptide multilayer nanofilms  

PubMed Central

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.

Jiang, Bingbing; Li, Bingyun

2009-01-01

294

Discontinued drugs in 2012: cardiovascular drugs.  

PubMed

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

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

2013-11-01

295

[Drug consumption and occupational violence in working women of Monterrey, N. L., Mexico].  

PubMed

The purpose of this study was to explore drug consumption and occupational violence in a sample of 669 adult women, working and living in 13 basic geostatistical areas of Monterrey, Nuevo León, México, using a descriptive correlational design with a qualitative approach. Results indicated that 37.1% of women consumed alcohol, 29.1% tobacco, 0.4% marihuana, 0.1% inhalants, and, among medical drugs, 5% consumed tranquilizers, and 1% other substances (barbiturates, antidepressive agents, Tylenol/codeine). The c2 test found no significant difference between sociodemographic and occupational factors and drug consumption (p<.05), except for the work form (c2=18.08, gl=4, p=.001). However, violence rate showed a positive association with drug consumption (p<.05). This study found 126 cases of violence, 34 of which narrated their experience. Drug consumption and violence perception was identified in 2 categories: Conceptualization of Occupational Violence and Relationship between Violence and Drug Consumption. PMID:16501787

Alonso Castillo, Maria Magdalena; Caufield, Catherine; Gómez Meza, Marco Vinicio

2005-01-01

296

Drug Reactions  

MedlinePLUS

... can also cause unwanted reactions. One problem is interactions, which may occur between Two drugs, such as ... and diseases, such as aspirin and peptic ulcers Interactions can change the actions of one or both ...

297

Generic Drugs  

MedlinePLUS

... example, there is a class of drugs, called statins, to treat high cholesterol. Some statins come as generics, while others do not. If you take a brand-name statin, ask if one of the generic statins would ...

298

Hazardous Drugs  

MedlinePLUS

... the work area. [ related topic page ] Standard Interpretations MSDS's must be provided to employees who package/process ... determination performed by the pharmaceutical manufacturer or importer. MSDS Requirements for Drugs . (1993, August 13). Provides a ...

299

Drug Reactions  

MedlinePLUS

... adverse drug reaction. One medicine might cause an adverse reaction if it’s taken with another medicine. One way ... reaction. Are prescription medicines the only cause of adverse reactions? No. Even medicines that you don't need ...

300

Thermodynamic analysis of binding between drugs and glycosaminoglycans by isothermal titration calorimetry and fluorescence spectroscopy.  

PubMed

The thermodynamics of the interaction of positively charged drug molecules with negatively charged glycosaminoglycans (GAGs) is investigated by isothermal titration calorimetry (ITC) and fluorescence spectroscopy. The drugs considered are propranolol hydrochloride, tacrine, and aminacrine, and the polymers used as model GAGs are dextran sulfate, chondroitin sulfate, and hyaluronic acid. The ITC results show that the interaction between drugs and GAGs is via direct binding and that GAGs bind to drugs at one set of sites. Large negative values of heat capacity change (DeltaC(p)) are observed upon binding of GAGs to drugs. Such negative DeltaC(p) is not expected for purely electrostatic interactions and suggests that hydrophobic and other interactions may be also involved in the binding process. These results are corroborated by fluorescence spectroscopy measurements, which show that specific drug/GAG complex formation is accompanied by a clear enhancement of the fluorescence intensity. The results highlight the importance of the formation of drug/GAG complexes as a primary step for the drug delivery process into cell membranes. It is concluded that the interactions are dependent on the nature of both GAG and drug and this is a fact to be taken into account when new drugs are designed. PMID:17643273

Santos, Hélder A; Manzanares, José A; Murtomäki, Lasse; Kontturi, Kyösti

2007-10-01

301

Mallory body induction in drug-primed mouse liver.  

PubMed

The aim of this study was to determine the various factors that are involved in the induction of Mallory body (MB) formation. A model was developed where MB formation was induced by refeeding either of the drugs griseofulvin or diethyl 1,4-dihydro-1,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC). Mice were fed the drugs for 5 months, followed by withdrawal of the drugs for 1 month (drug-primed livers). The drugs were refed for 1,3,5,7, or 11 days. Early MBs first appeared as small, enlarged aggregates of filaments in the perinuclear or pericanalicular location on the third day of refeeding. Mature MBs appeared on the fifth day of refeeding. MBs reached maximum concentration on day 5 of refeeding. Western blots showed a progressive increase in the cytokeratin proteins (CK49 and CK55) and actin while refeeding the drugs. Liver cell regeneration, as indicated by the percent of proliferating cell nuclear antigen (PCNA)-positive nuclei, increased on the third day of refeeding. However, there was no correlation between the frequency of MBs and the percent of PCNA-positive nuclei. It is concluded that MB formation is not related to the liver cell regeneration response to injury but rather involves a separate regulation pathway. The MBs were heavily ubiquitinated and were associated with increased ubiquitin-protein conjugates as indicated by Western blotting, suggesting that ubiquitinization of cytokeratin protein are involved in the formation of MB aggregation. PMID:8781332

Yuan, Q X; Marceau, N; French, B A; Fu, P; French, S W

1996-09-01

302

Educational Outreach: The Space Science Road Show  

NASA Astrophysics Data System (ADS)

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

Cox, N. L. J.

2002-01-01

303

[Use of methadone in obstetric and gynecologic management of drug-dependent females with and without HIV infection].  

PubMed

In the course of obstetrical and gynecological care, 113 women with acute intravenous drug use (IVD) participated in a methadon detoxification. In addition to medical treatment, socio-paedagogical intervention was part of the approach. A total of 212 cycles of methadon detoxification have been administered since patients' relapse during or after detoxication had a chance of readmission. In 45% of the attempts, detoxification could be fully achieved. An investigation of actual drug behaviour of the participating women in October 1990 showed, that 23.9% had abstained from drug consumption for at least 6 months ("drug free"). According to the HIV status and pregnancy 4 groups with comparable age (mean 27.7 years) and duration of drug dependency (mean 7.5 years) were classified. There were remarkable differences in drug behaviour between these groups. Of the HIV-infected women treated during pregnancy, 36% were drug free. Of the HIV-infected women without pregnancy and pregnant women without HIV-infection, comparable proportions (approx. 27% each) were living without drugs. All but one HIV-negative women of the group without pregnancy (3.8%) consumed drugs. In conclusion, pregnancy and subsequent motherhood seems to enhance and stabilize the motivation to quit drug consumption. The significant difference between the HIV-negative and HIV-positive women without pregnancy suggests, that besides pregnancy, the awareness of HIV-infection and of a limited life expectancy has also a positive influence on drug behaviour. PMID:1936870

Schäfer, A; Eck, M; Bell, U; Heckmann, W; Schwartländer, B

1991-08-01

304

Drug allergy  

PubMed Central

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

Warrington, Richard

2012-01-01

305

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

ERIC Educational Resources Information Center

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

Office of National Drug Control Policy, 2007

2007-01-01

306

Research Shows Ways to Speed Stroke Care  

MedlinePLUS

... Studies looked at improvements in ER, specially equipped ambulance that could deliver clot-busting drug (*this news ... Now, new efforts to hasten treatment in both ambulances and emergency rooms appear to have significantly improved ...

307

IPI-145 shows promise in CLL patients.  

PubMed

Results from a phase I study of Infinity Pharmaceuticals' IPI-145, which inhibits both ? and ? isoforms of phosphoinositide3-kinase, suggest the drug is safe and effective in patients with advanced chronic lymphocytic leukemia. PMID:24501284

2014-02-01

308

Letter position dysgraphia.  

PubMed

The article describes AE, a Hebrew-speaking individual with acquired dysgraphia, who makes mainly letter position errors in writing. His dysgraphia resulted from impairment in the graphemic buffer, but unlike previously studied patients, most of his errors related to the position of letters rather than to letter identity: 80% of his errors were letter position errors in writing, and only 7% of his errors were letter omissions, substitutions, and additions. Letter position errors were the main error type across tasks (writing to dictation and written naming), across output modalities (writing and typing), and across stimuli, e.g., migratable words (words in which letter migration forms another word), irregular words, and nonwords. Letter position errors occurred mainly in the middle letters of a word. AE's writing showed a significant length effect, and no lexicality, migratability, or frequency effects. His letter position deficit was manifested selectively in writing; he made no letter position errors in reading, demonstrating the dissociability of letter position encoding in reading and writing. These data support the existence of a letter order function in the graphemic buffer that is separate from the function responsible for activating letter identities. PMID:19846074

Gvion, Aviah; Friedmann, Naama

2010-10-01

309

DRUG NAME (INSERT DRUG NAME)  

Cancer.gov

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

310

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

Cancer.gov

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

311

Drug legalization, harm reduction, and drug policy.  

PubMed

The current U.S. policy options on drug use are reviewed in the context of the history of drug policy in the United States. A restrictive drug policy is a deterrent to drug use and helps reduce drug-related costs and societal problems. Although legalization or decriminalization of drugs might reduce some of the legal consequences of drug use, increased drug use would result in harmful consequences. PMID:7639447

DuPont, R L; Voth, E A

1995-09-15

312

Release of antithrombotic drugs from alginate gel beads.  

PubMed

The aim of the present work was to evaluate alginate hydrogels in the form of spherical beads as carrier for antithrombotic drugs for future use in artificial grafts. The ionotropic gelation technique was employed to prepare beads from the L. hyperborea stipe of alginate with two different alginate concentrations and two different guluronic to manuronic acid ratios. The beads were loaded, via soaking, with three different types of low molecular weight model molecules representing drugs with antithrombotic action and their release characteristics were subsequently evaluated. The entire release process of the negatively charged model drugs under study (Salicylic acid and Hirudin), was found to be governed by diffusion, while additional electrostatic interactions between drug molecule and alginate matrix was indicated to influence the release rate of the analyzed positively charged drug molecule (Dipyridamole). It was found that the alginate hydrogel matrix imposed a decrease of the drug diffusion rate on the molecules under study as compared to the corresponding diffusion rates in water. All diffusion coefficients decreased slightly with increasing concentration of alginate and with increasing guluronic to manuronic acid ratio. The results show on the potential use of alginate gel beads when developing vehicles for release of low molecular weight antithrombotic drugs. PMID:20695840

Jämstorp, Erik; Bodin, Aase; Gatenholm, Paul; Jeppsson, Anders; Strømme, Maria

2010-10-01

313

In silico modeling to predict drug-induced phospholipidosis.  

PubMed

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

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

2013-06-01

314

Drugs and the law: a psychological analysis of drug prohibition.  

PubMed

There is an ongoing American policy debate about the appropriate legal status for psychoactive drugs. Prohibition, decriminalization, and legalization positions are all premised on assumptions about the behavioral effects of drug laws. What is actually known and not known about these effects is reviewed. Rational-choice models of legal compliance suggest that criminalization reduces use through restricted drug availability, increased drug prices, and the deterrent effect of the risk of punishment. Research on these effects illustrates the need for a more realistic perspective that acknowledges the limitations of human rationality and the importance of moral reasoning and informal social control factors. There are at least 7 different mechanisms by which the law influences drug use, some of which are unintended and counterproductive. This framework is used to explore the potential behavioral effects of decriminalization and legalization. PMID:8316611

MacCoun, R J

1993-05-01

315

[Drug-induced pneumonitis associated PABRON-GOLD].  

PubMed

A 75-year-old man had for many years taken the commercially sold medicine PABRON-S whenever he caught a cold. He caught a cold and took the drug six days before admission. When PABRON-S was not available, he took PABRON-GOLD and experienced dyspnea the next day. A roentgenogram at another hospital revealed bilateral diffuse lung shadows. He was referred to our hospital. A thoracic CT scan showed bilateral interstitial shadows. Bronchoalveolar lavage fluid contained inflammatory cells including neutrophils and lymphocytes. Examination of a transbronchial lung biopsy specimen showed infiltration of mononuclear cells into the thick alveolar wall and interstitum. A drug lymphocyte stimulation test with PABRON-GOLD was positive. Based on these findings, we believe that this patient had drug-induced pneumonitis caused by PABRON-GOLD. He was treated with a steroid hormone and his symptoms resolved immediately, the abnormal roentgenographic shadows remained longer. PMID:9071160

Nomura, M; Fujimura, M; Matsuda, T; Kitagawa, M

1997-01-01

316

Drug signs and teenagers  

MedlinePLUS

Teenagers and drugs; Symptoms of drug use in teenagers; Drug abuse-teenages; Substance abuse-teenages: ... Institute on Drug Abuse: Preventing drug use among children and adolescents. NIH Publication No. 04-4212(B). ...

317

Cationic amphiphilic drugs self-assemble to the core-shell interface of PEGylated phospholipid micelles and stabilize micellar structure.  

PubMed

Since polymeric micelles are promising and have potential in drug delivery systems, people have become more interested in studying the compatibility of polymeric carriers and drugs, which might help them to simplify the preparation method and increase the micellar stability. In this article, we report that cationic amphiphilic drugs can be easily encapsulated into PEGylated phospholipid (PEG-PE) micelles by self-assembly method and that they show high encapsulation efficiency, controllable drug release and better micellar stability than empty micelles. The representative drugs are doxorubicin and vinorelbine. However, gemcitabine and topotecan are not suitable for PEG-PE micelles due to lack of positive charge or hydrophobicity. Using a series of experiments and molecular modelling, we figured out the assembly mechanism, structure and stability of drug-loaded micelles, and the location of drugs in micelles. Integrating the above information, we explain the effect of the predominant force between drugs and polymers on the assembly mechanism and drug release behaviour. Furthermore, we discuss the importance of pKa and to evaluate the compatibility of drugs with PEG-PE in self-assembly preparation method. In summary, this work provides a scientific understanding for the reasonable designing of PEG-PE micelle-based drug encapsulation and might enlighten the future study on drug-polymer compatibility for other polymeric micelles. PMID:24000361

Wang, Jing; Xing, Xueqing; Fang, Xiaocui; Zhou, Chang; Huang, Feng; Wu, Zhonghua; Lou, Jizhong; Liang, Wei

2013-10-13

318

Drug-induced hepatic injury.  

PubMed

Drugs and other chemical toxins account for less than 5% of cases of jaundice or acute hepatitis and fewer cases of chronic liver disease, but they are an important cause of more severe types of hepatic injury. Drug reactions produce an array of hepatic lesions that mimic all known hepatobiliary diseases; this poses a diagnostic challenge for physicians and pathologists. Diagnosis of drug-induced hepatic injury is circumstantial, with positive rechallenge being the only factor that unequivocally implicates a particular agent. Nonetheless, other aspects of the temporal relationship between drug ingestion and adverse reaction, exclusion of other diseases, the presence of extrahepatic features of drug hypersensitivity and some findings on liver biopsy can lend support to the diagnosis. Some of these issues will be explored in this review by considering contemporary paradigms of drug-induced hepatic injury. Factors that predispose to dose-dependent hepatic injury will be considered in relation to acetaminophen, an example of acute hepatotoxicity, and methotrexate, an agent that can produce hepatic fibrosis. Flucloxacillin will be discussed as an example of drug-induced cholestatic hepatitis often associated with prolonged cholestasis and the vanishing bile duct syndrome. Minocycline and diclofenac will be mentioned as two drugs for which drug hepatitis is an exceedingly rare complication. Finally, the evidence that Chinese herbal medicines can be hepatotoxic will be reviewed. PMID:9407344

Farrell, G C

1997-10-01

319

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

320

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

321

Assessment of Pharmacists Knowledge, Attitude and Practices Regarding Herbal Drug Information Services  

PubMed Central

Rational: Research suggests that increased consumption of herbal drugs is raising important public health concerns such as safety issues that may involve adverse effects and herb-drug interactions. The main objective of this study is to investigate the role of Pharmacists in herbal drug information dissemination. Method: We investigated the demographics, knowledge, attitude and practices regarding herbal drug information and regulatory laws among Pharmacists living in the six (6) States that constitute the Niger-Delta region of Nigeria. A total of 300 self-administered questionnaires were distributed to Pharmacists aged 21 years and above. Findings: About half of the respondents (48.72 %) were Hospital based Pharmacists. Knowledge of herbal drugs was 46.33 % while 64 .0 % showed positive attitude towards its use. Most of the information on herbal drugs were sourced from the internet (23.08 %) while 53.48 % were aware of the laws and regulations controlling herbal drugs in Nigeria. 88.64 % were in favour of the establishment of a National Herbal Drug Research and Development Agency and 55.68 % strongly agreeing to the setting up of a Herbal Drug Information Centre. Conclusion: The availability of herbal drug information services will not only enhance the performance of the Pharmacists, but will also add value to the life of the patients.

Atavwoda, Abere Tavs; Gabriel, Aina Ayodele

2012-01-01

322

Drug Hypersensitivity Reactions Involving Skin  

Microsoft Academic Search

Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside\\u000a immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions\\u000a appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely\\u000a skin involvement to fulminant systemic diseases which may

Oliver Hausmann; Benno Schnyder; Werner J. Pichler

323

Therapeutic drug monitoring of vancomycin.  

PubMed

Vancomycin, a glycopeptide antibiotic, was developed-and released in the 1950's for the treatment of aerobic gram-positive infections and has been widely used mainly in the treatment of methicillin-resistant Staphylococcus aureus infections. Early reports regarding the possibility of nephrotoxicity and ototoxicity led to concern about the use of vancomycin and the need to monitor serum concentrations. In Mexico, the National Institute of Cardiology measures serum level of some drugs, such as vancomycin on a routine basis. Nevertheless, although a large number of measurements are made, the quantification of drug in serum is only used by physicians as a empiric parameter for dose adjustment. The aim of this work was to know whether dosing was appropriate taking the therapeutic interval as a commonly accepted baseline and to propose viable alternatives in the case dosing was inadequate. Peak and through vancomycin levels were analyzed retrospectively (n=295), in patients from 18 to 65 yr old with diagnosis of sepsis. The relationship between administered dose and measured blood levels was established. The equation that characterizes the study population was obtained based on a single compartment model considering the proportional relationship between vancomycin and creatinine clearance. The analysis shows that only 44% of C(trough) and 47% of C(peak) values represented therapeutic levels, with the remainder either toxic or ineffective. PMID:22128413

Robles-Piedras, Ana Luisa; González-López, Eva Hilda

2009-01-01

324

Drug Tolerance in Mycobacterium tuberculosis  

Microsoft Academic Search

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

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

325

Chronic Myeloid Leukemia Patients Sensitive and Resistant to Imatinib Treatment Show Different Metabolic Responses  

PubMed Central

The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML). However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML) showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML) and patients resistant to imatinib (RCML) had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA). In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.

Wang, Guangji; Yan, Bei; Zhang, Sujiang; Huang, Qing; Ni, Lingna; Zha, Weibin; Liu, Linsheng; Cao, Bei; Hong, Ming; Wu, Hanxin; Lu, Hua; Shi, Jian; Li, Mengjie; Li, Jianyong

2010-01-01

326

drug monitoring  

Microsoft Academic Search

\\u000a (1) continuous measurements of drug concentrations in biological fluids or tissues for therapeutic or safety reasons; (2)\\u000a registry enrolling patients who are subject of a specific treatment (e.g. every American treated with thalidomide for leprosy\\u000a is required to enroll in a government\\/FDA-monitored registry); (3) ? see post-marketing surveillance.

Gerhard Nahler

327

Antihistamine Drugs  

MedlinePLUS

... products can be used more or less frequently. 5. For drugs available by prescription only, monthly costs reflect nationwide retail average prices for July 2010, rounded to the nearest dollar. Data is provided by Wolters Kluwer Pharma Solutions, which is not involved in our analysis or ...

328

Antineoplastic Drugs.  

ERIC Educational Resources Information Center

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…

Morris, Sara; Michael, Nancy, Ed.

329

Utilising Discursive Positioning in Counselling  

ERIC Educational Resources Information Center

Foucault's concern with the production of subjectivity has led to the development of positioning theory, as it has been called by Bronwyn Davies, Rom Harr and Luk van Langenhve. The concept of discursive positioning has particular value for counselling because it shows how people are positioned in discourse in particular moments by their own and…

Winslade, John M.

2005-01-01

330

Sun Position (Polar Coordinates)  

NSDL National Science Digital Library

This applet shows the current (realtime) Sun position as seen from a polar view above the North pole. The elevation and azimuth of the Sun are given, and a brief description of celestial coordinates and celestial spheres is covered as well. A demonstration of this applet is available to download.

Giesen, Juergen

331

DrugComboRanker: drug combination discovery based on target network analysis  

PubMed Central

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

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

2014-01-01

332

[Drug resistance testing of Mycobacterium tuberculosis isolates from sputum in Chad].  

PubMed

Culture and resistance testing of Mycobacterium tuberculosis are not regularly performed in Chad. Sputa were obtained from three different categories of hospitals (district, regional and national) in Chad. All examined sputa were smear-positive and were investigated by culture and drug resistance testing for first-line antituberculosis drugs. From 232 sputa positive for acid-fast bacilli, 135 isolates of M. tuberculosis from different patients (46 women, 89 men, mean age 34 years) were analyzed. All the patients except one corresponded to new cases of tuberculosis. In total, 27 out of 135 isolates (20%) were resistant to at least one major antituberculosis drug. Resistance to isoniazid was the most frequent resistance observed, with 18 isolates (13%) presenting at least this resistance. Three isolates (2.2%) were resistant to isoniazid and rifampicin (multidrug resistance MDR) including one isolate being concomitantly resistant to streptomycin and ethambutol. The resistance rate differed in relation to the category of the hospital; the most important resistance rate was observed in regional hospitals (33%), while it was 16% and 14% in the national and district hospitals, respectively. HIV serology was performed in 81 patients, among whom 20 (25%) were positive. This is the first study that shows that drug resistance of M. tuberculosis is present in Chad. Besides single drug-resistant isolates, multidrug-resistant strains of M. tuberculosis could also be identified. This result highlights the urgency of initiating actions to detect drug resistance and limit the spread of drug-resistant strains. PMID:21960358

Abdelhadi, O; Ndokaïn, J; Ali, M Moussa; Friocourt, V; Mortier, E; Heym, B

2012-02-01

333

Short communication Club drug use among college students  

Microsoft Academic Search

This study examined prevalence and frequency of bclubQ drug use among college students (N=831) and associations with marijuana and alcohol use, sensation seeking, and positive and negative affectivity. Eighteen percent (n=146) of the sample had used club drugs at least once in their lifetime. Results of a logistic regression indicated that club drug use was positively associated with marijuana use,

Jeffrey S. Simons; Raluca M. Gaher; Christopher J. Correia; Jacqueline A. Bush

334

832 Karin Shows No Rotational Spectral Variations  

NASA Astrophysics Data System (ADS)

Sasaki et al. (2004, 2005) claimed that 832 Karin, the brightest member of the very young (5.75 Myr) Karin cluster of the Koronis family, shows dramatically different colors as a function of rotational phase. It was interpreted that Karin is a fragment of the recently broken-up asteroid, showing the reddish space-weathered exterior surface of the precursor asteroid as well as an interior face, which has not had time to become space-weathered. On five nights during UT 7-14 January 2006, we observed Karin with the SpeX instrument, 0.8-2.5 microns, on the IRTF. We sampled its spectrum well throughout its rotation. We analyzed the data in 50 deg. intervals of rotational longitude; some longitudes were sampled during two different nights. We find that Karin exhibits minimal spectral variations with rotation, certainly nothing of the magnitude reported by Sasaki et al. Since our data resemble Sasaki et al.'s "blue" and "green" sets, we suggest that their "red" set is spurious. Indeed, it is difficult to understand how the reported color change could have occurred during such a modest interval ( 4%) of rotational longitude. (Note that we have not determined Karin's pole position nor the phase of the Sasaki et al. data within our own coverage, so the refutation of dramatic color change is not absolutely secure.) Karin and its family members are not quite as red as typical S-types, yet have shallow absorption bands. Perhaps the space-weathering process affecting these young asteroids has had time to reduce spectral contrast, but has not operated long enough to redden them -- an intermediate case of space weathering, which has gone to completion for older main-belt asteroids of these sizes. Supported by the NASA Planetary Astronomy Program. T. Sasaki et al. 2004. ApJ 615, L161-L164; T. Sasaki et al. 2005. LPSC XXXVI, 1590.pdf.

Chapman, Clark R.; Enke, B.; Merline, W. J.; Nesvorny, D.; Tamblyn, P.; Young, E. F.

2006-09-01

335

Discovery helps show how breast cancer spreads  

Cancer.gov

Researchers at Washington University School of Medicine in St. Louis (home of the Alvin J. Siteman Cancer Center) have discovered why breast cancer patients with dense breasts are more likely than others to develop aggressive tumors that spread. The finding opens the door to drug treatments that prevent metastasis.

336

Downfall: Sports and Drugs (Closed Captioned).  

National Technical Information Service (NTIS)

This show profiles athletes whose careers were disrupted by drugs, especially steroids. Scene of the athletes performing are mixed with present day. Sobering interviews, the video examines the consequences of drugs on all aspects of an athlete's life-care...

1994-01-01

337

Environmental Effects on Drug Use  

ERIC Educational Resources Information Center

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,…

Russell, James A.; Mehrabian, Albert

1977-01-01

338

Therapeutic drug monitoring: antiarrhythmic drugs  

PubMed Central

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

Campbell, T J; Williams, K M

1998-01-01

339

Prevalence of tuberculosis drug resistance in 10 provinces of China  

PubMed Central

Background The emergence of drug-resistant tuberculosis (TB) hampers TB control. Ten provinces in China performed drug resistance surveys among tuberculosis (TB) patients in 1996–2004 to assess levels of drug resistance. Methods Provincial drug resistance surveys included all isolates from newly diagnosed, smear-positive TB patients. Drug susceptibility testing (DST) against isoniazid, rifampicin, streptomycin and ethambutol was carried out in the provincial laboratories. For purposes of quality assurance, a random sample (11.6%) was re-tested by the national reference laboratory (NRL). Results Of 14,059 patients tested 11,052 (79%) were new TB cases. The weighted mean prevalence of multi-drug resistant tuberculosis (MDR-TB) among all cases was 9.3% (range 2.2%–10.4%); 5.4% (range 2.1% – 10.4%) among new cases and 25.6% (range 11.7%–36.9%) among previously treated cases. Adjusting the drug resistance proportions using the re-testing results did not change the estimated national mean prevalence significantly. However, in some individual provinces the estimated resistance proportions were greatly influenced, especially among re-treatment patients. Conclusion MDR-TB levels varied greatly between provinces in China, but on average were high compared to the global estimated average of 4.8%. This study shows the importance of quality-assured laboratory performance. Programmatic management of drug-resistant TB, including high quality DST for patients at high risk of resistance and treatment with second-line drugs, should become the standard, especially in high MDR-TB settings.

He, Guang Xue; Zhao, Yan Lin; Jiang, Guang Lu; Liu, Yu Hong; Xia, Hui; Wang, Sheng Fen; Wang, Li Xia; Borgdorff, Martien W; van der Werf, Marieke J; van den Hof, Susan

2008-01-01

340

Use of illicit drugs by truck drivers arriving at paranaguá port terminal, Brazil.  

PubMed

Objective: The purpose of this study was to estimate the prevalence of recent use of illicit drugs among truck drivers who had parked their vehicles at the terminal port in Paranaguá City at Paraná State, southern Brazil. Methods: This cross-sectional study was part of a larger research project conducted among drivers at a regional Brazilian port. Data on professional characteristics, involvement in road traffic injuries, sleep, and use of alcohol and illicit drugs were collected using a questionnaire. Urine samples were collected and analyzed for amphetamines, cocaine, and cannabis using gas chromatography with mass spectrometric detection. Results: Sixty-two drivers were included in the study. Toxicological analyses showed that 8.1 percent (95% confidence interval [CI], 2.7-17.8%) of the urine samples were positive for drugs (4.8% for cocaine, 1.6% for amphetamine, and 1.6% for both); 8.1 percent reported drug use during the preceding 30 days in the questionnaire and only one tested positive for the drug in the urine sample. No sample was positive for cannabinoids. In total, at least 14.5 percent (95% CI, 6.9-25.8%) had used illicit drugs during the preceding 30 days based on self-reports and urine testing. Drivers who reported involvement in traffic injuries the year before more often tested positive for drugs in biological samples (P <.05). Conclusions: This research provides preliminary evidence that the use of illicit stimulants was common among professional truck drivers transporting grain loads. Thus, actions are needed to reduce drug use among truck drivers in order to prevent drug-related road traffic injuries. PMID:24313348

Peixe, Tiago Severo; de Almeida, Rafael Menck; Girotto, Edmarlon; de Andrade, Selma Maffei; Mesas, Arthur Eumann

2014-10-01

341

Microelectronic control of drug delivery.  

PubMed

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

Guo, Xin Dong; Prausnitz, Mark R

2012-07-01

342

Drug-induced peripheral neuropathies.  

PubMed

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

Argov, Z; Mastaglia, F L

1979-03-10

343

Pharmacogenetics of anxiolytic drugs  

Microsoft Academic Search

Acute and chronic anxiety represents the core symptoms in anxiety disorders. Anxiolytic pharmacological treatment mainly consists\\u000a in administration of benzodiazepines and antidepressants. Whereas benzodiazepines show little, antidepressants show a relative\\u000a large interindividual variability in terms of drug response where about one-third of patients do not respond at all. With\\u000a no meaningful predictors available, there is increasing hope that genetics can

Arun K. Tiwari; Renan P. Souza; Daniel J. Müller

2009-01-01

344

Antipsychotic Drugs  

PubMed Central

Sudden cardiac death has become a significant clinical concern when prescribing antipsychotic drugs, especially to older people with dementia. Sudden death syndrome has been known for decades to occur in association with taking first-generation antipsychotic medications, but it has become more prominent recently due to safety reviews about the use of second-generation antipsychotic medications. In 2005, the United States Food and Drug Administration disseminated information about cardiac fatalities, which led to black box warnings in second-generation, antipsychotic, drug-prescribing literature about higher mortality when administering to elderly persons with dementia-related psychoses. In this population, treatment results in death rates of 4.5 percent, as compared to 2.6 percent in subjects taking a placebo. Actually, patients treated with both the first- and second-generation versions experienced an increased incidence of fatalities. Before utilizing these agents, a careful workup must be completed. The presence of a psychosis or mania should be the only conventional indication for prescribing first- and second-generation antipsychotic medications. Physicians should always evaluate patients for comorbid conditions, especially heart disease and metabolic abnormalities, and all currently used medications to assure a risk-to-benefit ratio favoring the application of an antipsychotic medication. An electrocardiogram is a part of the evaluation of the cardiac status and determines the base line QT interval. While prescribing these medications in elderly patients, physicians must provide individualized clinical, electrocardiographic, and pharmaceutical monitoring.

Narang, Puneet; El-Refai, Mostafa; Parlapalli, Roop; Danilov, Lilia; Manda, Sainath; Kaur, Gagandeep

2010-01-01

345

Psychophysiological prediction of choice: relevance to insight and drug addiction.  

PubMed

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

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

2012-11-01

346

Psychophysiological prediction of choice: relevance to insight and drug addiction  

PubMed Central

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

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

2012-01-01

347

Club Drugs: An Update. Drug Intelligence Brief.  

National Technical Information Service (NTIS)

Club Drugs is a general term for a number of illicit drugs, primarily synthetic, that are most commonly encountered at nightclubs and 'raves.' The drugs include MDMA, ketamine, GHB, GBL, Rohypnol, LSD, PCP, methamphetamine, and, to a lesser extent, psiloc...

2001-01-01

348

Overview of Club Drugs. Drug Intelligence Brief.  

National Technical Information Service (NTIS)

Club Drugs is a general term for a number of illicit drugs, primarily synthetic, that are most commonly encountered at nightclubs and 'raves.' The drugs include MDMA, Ketamine, GHB, GBL, Rohypnol, LSD, PCP, methamphetamine, and, to a lesser extent, cocain...

2000-01-01

349

Photomechanical drug delivery  

NASA Astrophysics Data System (ADS)

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.

Doukas, Apostolos G.; Lee, Shun

2000-05-01

350

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

PubMed

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

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

2014-07-11

351

Spirit Wiggles into Position  

NASA Technical Reports Server (NTRS)

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).

2005-01-01

352

Modulation of trichloroethylene in vitro metabolism by different drugs in rats.  

PubMed

Trichloroethylene (TCE) is a widely used chemical to which humans are frequently exposed. Toxicological interactions with drugs are among factors having the potential to modulate the toxicity of TCE. The aim of this study was to identify metabolic interactions between TCE and 14 widely used drugs in rat suspended hepatocytes and characterize the strongest using microsomal assays (oxidation and/or glucuronidation). The concentrations of TCE and its metabolites, trichloroethanol (TCOH) and trichloroacetate (TCA), were measured by gas chromatography with injection headspace coupled to mass spectrometry (GC-MS). Results in hepatocyte incubations show that selected drugs can be segregated into four groups: group 1: drugs causing no significant interactions (five drugs: amoxicillin, carbamazepine, ibuprofen, mefenamic acid and ranitidine); group 2: increasing both TCE metabolites (two drugs: naproxen and salicylic acid); group 3: decreasing both TCE metabolites (five drugs: acetaminophen, gliclazide, valproic acid, cimetidine and diclofenac) and group 4: affecting only one (two drugs: erythromycin and sulphasalazine). Naproxen and salicylic acid (group 2) and acetaminophen, gliclazide and valproic acid (from group 3) presented the strongest interactions (i.e. drugs changing metabolite levels by 50% or more). For group 2 drugs, characterization in rat microsomes confirmed interaction with naproxen only, which was found to partially competitively inhibit TCOH glucuronidation (K(i) = 211.6 ?M). For group 3 selected drugs, confirmation was positive only for gliclazide (K(i) = 58 ?M for TCOH formation) and valproic acid (K(i) = 1215.8 ?M for TCA formation and K(i) = 932.8 ?M for TCOH formation). The inhibition was found to be partial non competitive for both drugs. Our results confirm the existence of interactions between TCE and a variety of widely used drugs. Further efforts are undertaken to determine if these interactions are plausible in humans and if they can impact the risk of toxicity of TCE in medicated population. PMID:23089131

Cheikh Rouhou, Mouna; Rheault, Isabelle; Haddad, Sami

2013-02-01

353

A Patient Education Program to Improve Adherence Rates with Antituberculosis Drug Regimens.  

ERIC Educational Resources Information Center

An incentive scheme to reward positive health behaviors (adherence to antituberculosis drug regimens) was tested with 88 active and 117 preventive patients randomly assigned to intervention and control groups. Preventive patients who received incentives were significantly more likely to continue care and had higher adherence levels. Actives showed

Morisky, Donald E.; And Others

1990-01-01

354

One Dimensional Motion: Position versus Time Graphs  

NSDL National Science Digital Library

In the following exercises, the graph drawn is of position versus time. The animation shows the position of a puck as time progresses. Note the position of the puck at various times and compare the animation to the graph.

Christian, Wolfgang; Belloni, Mario

2008-02-19

355

Treating Prescription Drug Addiction  

MedlinePLUS

... information about prescription drug abuse? Glossary References NIDA Publications By Audience By Drug of Abuse By Drug ... of national interest. View all ?Research Reports Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ...

356

Prescription Drug Abuse  

MedlinePLUS

... information about prescription drug abuse? Glossary References NIDA Publications By Audience By Drug of Abuse By Drug ... Unused Medicines: What You Should Know (FDA) Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ...

357

Drugs and their effects  

NSDL National Science Digital Library

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

Olivia Worland (Purdue University;Biological Sciences)

2008-07-07

358

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.

359

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.

360

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.

361

Antiplatelet Drugs  

PubMed Central

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

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

2012-01-01

362

drug sales  

Microsoft Academic Search

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

Gerhard Nahler

363

Drugs and the Brain.  

ERIC Educational Resources Information Center

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…

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

364

A Mysterious Gram-Positive Rods  

PubMed Central

We encountered a patient with a history of intravenous drug use presenting with fever, malaise and nausea who was found to have cavitary lung lesions. Unexpectedly, gram positive rods grew out on day five on multiple blood cultures, which were later identified as Mycobacterium fortuitum. The patient underwent transesophageal echocardiogram, which showed aortic and tricuspid valve vegetations. Liver biopsy demonstrated granulomatous hepatitis. Interestingly, serum alkaline phosphatase level fell with antibiotic treatment. Mycobacterium fortuitum is ubiquitous worldwide, being found in tap water, and soil. M. fortuitum is usually considered as a contaminant. Disseminated infection caused by this bacterium in an immunocompetent host is extremely rare. Most of the disseminated infections have been reported in immune-deficient patients. In immunocompetent people, M. fortuitum causes human infection primarily by direct inoculation, including localized post-traumatic and surgical wound infections, and catheter-related sepsis. Our patient, an HIV-negative intravenous drug user, had Mycobacterium fortuitum sepsis associated with infective endocarditis, septic pulmonary emboli, and granulomatous hepatitis. Interestingly, the patient admitted using tap water occasionally for mixing heroin when her sterile water ran out, which we thought was the likely source of M. fortuitum.

Natsag, Javzandulam; Min, Zaw; Hamad, Yasir; Alkhalil, Bassel; Rahman, Atiq; Williams, Richard

2012-01-01

365

Intelligence and Past Use of Recreational Drugs  

ERIC Educational Resources Information Center

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

Wilmoth, Daniel R.

2012-01-01

366

Drug Control: State Approaches Taken to Control Access to Key Methamphetamine Ingredient Show Varied Impact on Domestic Drug Labs.  

National Technical Information Service (NTIS)

Meth can be made by anyone using easily obtainable household goods and consumer products in labs, posing significant public safety and health risks and financial burdens to local communities and states where the labs are found. Meth cooks have discovered ...

2013-01-01

367

Drugs and sexual behavior.  

PubMed

This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed. PMID:23457886

Bruno, Antonio; Scimeca, Giuseppe; Marino, Antonio G; Mento, Carmela; Micò, Umberto; Romeo, Vincenzo M; Pandolfo, Gianluca; Zoccali, Rocco; Muscatello, Maria R A

2012-01-01

368

Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.  

PubMed

The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs. PMID:20631867

Harris, Ruth; Lecumberri, Elena; Heras, Angeles

2010-01-01

369

Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin  

PubMed Central

The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 ?m. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

Harris, Ruth; Lecumberri, Elena; Heras, Angeles

2010-01-01

370

Adsorption of drugs onto a pH responsive poly(N,N-dimethyl aminoethyl methacrylate) grafted anion-exchange membrane in vitro.  

PubMed

The influence of charge and lipophilicity of acidic and basic model drugs on their adsorption onto poly(N,N-dimethyl aminoethyl methacrylic acid) grafted poly(vinylidene fluoride) (DMAEMA-PVDF) membranes was evaluated. The effect of serum proteins (albumin, IgG) and hormones (cortisol, free thyroxine (T(4)F) and thyrotropin (TSH)) on drug adsorption was also studied. Acidic model drugs (antiepileptics and benzodiazepies) adsorbed to a greater extent onto the membrane from Hepes buffer at ionic strength of 25mM and pH 7.0 than basic drugs (antidepressants) did. Adsorption of acidic model drugs was based on electrostatic interactions between positively charged tertiary amino groups of DMAEMA side-chain and acidic negatively charged drug. Albumin diminished the adsorption of drugs from serum onto the membrane. Lipophilicity was related to the adsorption of acidic model drugs from serum onto the membrane. The degree of grafting had the greatest effect on adsorption of lipophilic drugs, but no influence was observed on adsorption of hydrophilic drugs. The present results showed that acidic drugs and albumin adsorbed onto the membrane, which suggests that the PVDF-DMAEMA membrane may be suitable for separating acidic drugs from protein-free substances for subsequent monitoring and evaluation. PMID:17289313

Karppi, Jouni; Akerman, Satu; Akerman, Kari; Sundell, Annika; Nyyssönen, Kristiina; Penttilä, Ilkka

2007-06-29

371

Intracochlear Drug Delivery Systems  

PubMed Central

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

Borenstein, Jeffrey T.

2011-01-01

372

Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany.  

PubMed

There is a need for quick and reliable methods for rapid screening of drug-influenced drivers on the roadside by police. Because the window of detection in oral fluid is more similar to blood than to urine, this matrix should therefore be appropriate for screening procedures. The performance of the Rapid STAT(®) (Mavand Solution GmbH, Mössingen, Germany), DrugWipe5/5+(®) (Securetec Detektions-Systeme AG, Brunnthal, Germany) and Dräger DrugTest(®) 5000 (Draeger Safety AG & Co. KGaA, Luebeck, Germany) on-site oral fluid devices was evaluated with random oral fluid specimens from car drivers in North Rhine-Westphalia (Germany). Additionally, some drivers were checked using an on-site urine device (DrugScreen(®), NAL von Minden, Regensburg, Germany). During a 11-month period, 1.212 drivers were tested. Both OF and urine on-site tests were compared to serum results. The following sensitivities were obtained by the oral fluid devices: THC 71% (DrugWipe(®)), 87% (Dräger), 91% (RapidSTAT); opiates 95% (Dräger), 100% (DrugWipe(®), RapidSTAT(®)); amphetamine 84% (DrugTest(®) 5000), 90% (RapidSTAT(®)), 100% (DrugTest(®) 5000); methamphetamine 50% (DrugTest(®) 5000), 100% (RapidSTAT(®)); cocaine 76% (DrugTest(®) 5000), 100% (DrugWipe(®), RapidSTAT(®)); methadone 33-63%, and benzodiazepines 0-33% (both with a low number of positives). THC specificity was especially low (29% [DrugWipe(®)] and 47% [DrugTest(®) 5000]) due to low cut-off concentrations. These data were similar to those obtained from the literature (e.g., DRUID project). The urine screening device showed a good sensitivity (THC 93%, opiate 94%, amphetamine 94%, methamphetamine 75% (low number of positives), cocaine 100%) and also an acceptable specificity (39%, 86%, 63%, 77%, 47%, respectively). Although oral fluid may be a useful matrix for on-site testing of drugged drivers, it is evident that oral fluid devices still show a lack of sensitivity (methamphetamine, benzodiazepines) and specificity (THC). Poor results for benzodiazepines may be explained by the small positive test number. Although the sensitivity for THC came out higher than compared to the literature, specificity is not yet satisfactory (only <90%). Furthermore, specificity was poor due to lowered cut-offs resulting in multiple false positive tests. PMID:24699311

Musshoff, Frank; Hokamp, Eva Große; Bott, Ulrich; Madea, Burkhard

2014-05-01

373

Developmentally vitamin D-deficient rats show enhanced prepulse inhibition after acute ?9-tetrahydrocannabinol.  

PubMed

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we aimed to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, ?-tetrahydrocannabinol (THC), on tasks of relevance to the cognitive and positive symptoms of schizophrenia. The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. Adult control and DVD-deficient rats were injected with THC (0, 0.3, 0.6, 1.25, 2.5 mg/kg) 15 min before a delay match to sample (DMTS) task using variable delays (0-24 s). A separate group of rats was injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response or in the open field. Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was observed at 2.5 mg/kg for all delays (0-24 s). DVD-deficient rats showed THC-induced enhancement of PPI, which was not observed in control rats. There was no effect of maternal diet on acoustic startle response or locomotor responses in the open field. This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on sensitivity to the behavioural effects of cannabinoids. PMID:24776491

Burne, Thomas H J; Alexander, Suzanne; Turner, Karly M; Eyles, Darryl W; McGrath, John J

2014-06-01

374

Absolute Positioning Using the Global Positioning System.  

National Technical Information Service (NTIS)

The Global Positioning System (GPS) has become a useful tool in providing relative survey control. The relative positioning accuracies of the GPS are commonly on the order of 1-10 parts per million (ppm). The drawback with relative positioning is the user...

B. A. Fosburgh T. M. Cox

1994-01-01

375

Hitchhiking Under Positive Darwinian Selection  

Microsoft Academic Search

Positive selection can be inferred from its effect on linked neutral variation. In the restrictive case when there is no recombination, all linked variation is removed. If recombination is present but rare, both deterministic and stochastic models of positive selection show that linked variation hitchhikes to either low or high frequencies. While the frequency distribution of variation can be influenced

Justin C. Fay; Chung-I Wu

2000-01-01

376

High Prevalence of Drug Resistance in Animal Trypanosomes without a History of Drug Exposure  

PubMed Central

Background Trypanosomosis caused by Trypanosoma congolense is a major constraint to animal health in sub-Saharan Africa. Unfortunately, the treatment of the disease is impaired by the spread of drug resistance. Resistance to diminazene aceturate (DA) in T. congolense is linked to a mutation modifying the functioning of a P2-type purine-transporter responsible for the uptake of the drug. Our objective was to verify if the mutation was linked or not to drug pressure. Methodology/Principal Findings Thirty-four T. congolense isolates sampled from tsetse or wildlife were screened for the DA-resistance linked mutation using DpnII-PCR-RFLP. The results showed 1 sensitive, 12 resistant and 21 mixed DpnII-PCR-RFLP profiles. This suggests that the mutation is present on at least one allele of each of the 33 isolates. For twelve of the isolates, a standard screening method in mice was used by (i) microscopic examination, (ii) trypanosome-specific 18S-PCR after 2 months of observation and (iii) weekly trypanosome-specific 18S-PCR for 8 weeks. The results showed that all mice remained microscopically trypanosome-positive after treatment with 5 mg/kg DA. With 10 and 20 mg/kg, 8.3% (n?=?72) and 0% (n?=?72) of the mice became parasitologically positive after treatment. However, in these latter groups the trypanosome-specific 18S-PCR indicated a higher degree of trypanosome-positivity, i.e., with a unique test, 51.4% (n?=?72) and 38.9% (n?=?72) and with the weekly tests 79.2% (n?=?24) and 66.7% (n?=?24) for 10 and 20 mg/kg respectively. Conclusion/Significance The widespread presence of the DA-resistance linked mutation in T. congolense isolated from wildlife suggests that this mutation is favourable to parasite survival and/or its dissemination in the host population independent from the presence of drug. After treatment with DA, those T. congolense isolates cause persisting low parasitaemias even after complete elimination of the drug and with little impact on the host's health.

Chitanga, Simbarashe; Marcotty, Tanguy; Namangala, Boniface; Van Den Abbeele, Jan; Delespaux, Vincent

2011-01-01

377

Flat Globe: Showing the Changing Seasons  

NSDL National Science Digital Library

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

Allen, Jesse; Newcombe, Marte; Feldman, Gene

1998-09-09

378

The Franklin Institute's Traveling Science Shows  

NSDL National Science Digital Library

The Franklin Institute's team of science educators are available for shows on a variety of science topics. Traveling Science shows are aligned with National Science Education Standards, and focus on Physics, Biology and Chemistry.

Shows, Traveling S.

2004-04-05

379

Bone Effects of Biologic Drugs in Rheumatoid Arthritis  

PubMed Central

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF?, IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF?, IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

2013-01-01

380

A Learning Model of Trade Show Attendance  

Microsoft Academic Search

This study examines trade show attendees' show choice behavior from a learning perspective. The purpose is to create a model that can be useful in attracting attendees, either to a show or even to a specific booth. Reasons for attending were found to be three-dimensional: shopping, career development, and general industry awareness. These dimensions were then used to develop clusters,

John F. Tanner Jr; Lawrence B. Chonko; Thomas V. Ponzurick

2001-01-01

381

The Wonders of Physics Traveling Show  

NSDL National Science Digital Library

The Wonders of Physics is a live physics show designed to stimulate interest in science in people of all ages and backgrounds. The program's fast-paced presentation is supplemented by a variety of media tools. In addition, a smaller traveling show is based in Madison, WI, but does shows all over the United States and Canada.

Physics, The W.

2004-06-02

382

Duke study shows that oral drug may improve survival in men with metastatic prostate cancer  

Cancer.gov

An investigational prostate cancer treatment slows the disease’s progression and may increase survival, especially among men whose cancer has spread to the bones, according an analysis led by the Duke Cancer Institute.

383

Study led by UC Irvine shows drug combo better for certain metastatic breast cancer:  

Cancer.gov

Post-menopausal women with a certain type of metastatic breast cancer may have a new treatment option that could lengthen their lives, according a study led by UC Irvine... The findings were presented today at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

384

Construction of drug network based on side effects and its application for drug repositioning.  

PubMed

Drugs with similar side-effect profiles may share similar therapeutic properties through related mechanisms of action. In this study, a drug-drug network was constructed based on the similarities between their clinical side effects. The indications of a drug may be inferred by the enriched FDA-approved functions of its neighbouring drugs in the network. We systematically screened new indications for 1234 drugs with more than 2 network neighbours, 36.87% of the drugs achieved a performance score of Normalized Discounted Cumulative Gain in the top 5 positions (NDCG@5) ? 0.7, which means most of the known FDA-approved indications were well predicted at the top 5 positions. In particular, drugs for diabetes, obesity, laxatives and antimycobacterials had extremely high performance with more than 80% of them achieving NDCG@5 ? 0.7. Additionally, by manually checking the predicted 1858 drug-indication pairs with Expression Analysis Systematic Explorer (EASE) score ? 10(-5) (EASE score is a rigorously modified Fisher exact test p value), we found that 80.73% of such pairs could be verified by preclinical/clinical studies or scientific literature. Furthermore, our method could be extended to predict drugs not covered in the network. We took 98 external drugs not covered in the network as the test sample set. Based on our similarity criteria using side effects, we identified 41 drugs with significant similarities to other drugs in the network. Among them, 36.59% of the drugs achieved NDCG@5 ? 0.7. In all of the 106 drug-indication pairs with an EASE score ? 0.05, 50.94% of them are supported by FDA approval or preclinical/clinical studies. In summary, our method which is based on the indications enriched by network neighbors may provide new clues for drug repositioning using side effects. PMID:24505324

Ye, Hao; Liu, Qi; Wei, Jia

2014-01-01

385

11. CALIFORNIATYPE DEPRESSION BEAM: Photocopy of photograph showing a Californiatype ...  

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

11. CALIFORNIA-TYPE DEPRESSION BEAM: Photocopy of photograph showing a California-type depression beam positioned in its yokes. A car would approach the beam moving towards the camera. Note the open access cover, pulleys, counterweight hatchcover, and the wooden construction of the beam. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

386

72. View of test system showing Klystron tube installed in ...  

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

72. View of test system showing Klystron tube installed in test position on first floor of transmitter building no. 102. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

387

7. Photocopy of photograph showing four Ajax missiles in launch ...  

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

7. Photocopy of photograph showing four Ajax missiles in launch position from ARADCOM Argus pg. 14, from Institute for Military History, Carlisle Barracks, Carlisle, PA, October 1, 1963 - NIKE Missile Battery PR-79, East Windsor Road south of State Route 101, Foster, Providence County, RI

388

5. FLOOR 3; SHOWS BRAKE LEVER, BLOCK FORMERLY USED TO ...  

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

5. FLOOR 3; SHOWS BRAKE LEVER, BLOCK FORMERLY USED TO RAISE IT AND HOOK WHICH KEPT IT IN THE 'OFF' POSITION; ALSO SEEN ARE THE LARGE BLOCKS SUSPENDED FROM THE CAP FRAME WHICH HOLD THE TRUCK WHEELS TO CENTER THE CAP - Hayground Windmill, Windmill Lane, East Hampton, Suffolk County, NY

389

Impact of Psychotropic Drugs on QT Interval Dispersion in Adult Patients  

PubMed Central

Background Drug-induced increase in QT dispersion has been associated with potentially fatal ventricular arrhythmias. Little is known about the use of psychotropic substances, alone or in combination with other drugs on QT dispersion. Objectives To evaluate the impact of psychotropic drugs on QT interval dispersion in adults. Methods An observational cohort study was designed involving 161 patients hospitalized from an emergency department at a tertiary hospital, divided into psychotropic users or non-users. Demographic, clinical, laboratory data and drugs used on a regular basis were collected on admission, in addition to 12-lead electrocardiogram with QT dispersion measurement. Results QT dispersion was significantly higher in the psychotropic user group compared to non-users (69.25 ± 25.5 ms vs. 57.08 ± 23.4 ms; p = 0.002). The QT interval corrected by Bazzett formula was also higher in the psychotropic drugs user group, with statistical significance. (439.79 ± 31.14 ms vs. 427.71 ± 28.42 ms; p = 0.011). A regression analysis model showed a positive association between the number of psychotropic drugs used and QT interval dispersion, with r = 0.341 and p < 0.001. Conclusions The use of psychotropic drugs was associated with increased QT dispersion and this increase was accentuated, as the number of psychotropic drugs used was higher.

Claudio, Bruno de Queiroz; Costa, Marcelle Azevedo Nossar; Penna, Filipe; Konder, Mariana Teixeira; Celoria, Bruno Miguel Jorge; de Souza, Luciana Lopes; Pozzan, Roberto; Schneider, Roberta Siuffo; Albuquerque, Felipe Neves; Albuquerque, Denilson Campos

2014-01-01

390

Sport participation and alcohol and illicit drug use in adolescents and young adults: a systematic review of longitudinal studies.  

PubMed

Sport participation can play an important and positive role in the health and development of children and youth. One area that has recently been receiving greater attention is the role that sport participation might play in preventing drug and alcohol use among youth. The current study is a systematic review of 17 longitudinal studies examining the relationship between sport participation and alcohol and drug use among adolescents. Results indicated that sport participation is associated with alcohol use, with 82% of the included studies (14/17) showing a significant positive relationship. Sport participation, however, appears to be related to reduced illicit drug use, especially use of non-cannabis related drugs. Eighty percent of the studies found sport participation associated with decreased illicit drug use, while 50% of the studies found negative association between sport participation and marijuana use. Further investigation revealed that participation in sports reduced the risk of overall illicit drug use, but particularly during high school; suggesting that this may be a critical period to reduce or prevent the use of drugs through sport. Future research must better understand what conditions are necessary for sport participation to have beneficial outcomes in terms of preventing alcohol and/or illicit drug use. This has been absent in the extent literature and will be central to intervention efforts in this area. PMID:24290876

Kwan, Matthew; Bobko, Sarah; Faulkner, Guy; Donnelly, Peter; Cairney, John

2014-03-01

391

Regulation of Drug Intake  

Microsoft Academic Search

Regulation of drug intake refers to the maintenance of relatively constant levels of drug over a specified time period. An understanding of regulation of drug intake may be critical in determining how drugs function as reinforcers and how their reinforcing effects may be modified. However, little is known about regulation of drug intake, and the mechanisms underlying it are poorly

Wendy J. Lynch; Marilyn E. Carroll

2001-01-01

392

Effects of Drug Abuse  

MedlinePLUS

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

393

Global Positioning Systems (GPS)  

NSDL National Science Digital Library

View an animated Flash slide show explaining how GPS works. GPS operates because of three interconnected segments: the satellite, ground control, and user segments. This animation focuses on the satellite and user segments, briefly touching upon how the satellite signal is processed to produce positional values in hand-held GPS units. Note that the accuracy claimed for handheld GPS units 100 m is now routinely exceeded. With the turning off of selective availability, today's GPS handheld units usually get accuracies of better than 10 meters. Note that the video loads slowly.

Wiley

394

Solar System Odyssey - Fulldome Digital Planetarium Show  

NSDL National Science Digital Library

This is a Fulldome Digital Planetarium Show. Learners go on a futuristic journey through our Solar System. They explore the inner and outer planets, then the moons: Titan, Europa, and Callisto as possible places to establish a human colony. A full-length preview of the show is available on the website, you need to scroll down about 3/4 of the page - under section on children's shows, direct link not available.

395

Signify ER Drug Screen Test evaluation: comparison to Triage Drug of Abuse Panel plus tricyclic antidepressants.  

PubMed

Signify ER Drug Screen Test (Signify ER) and Triage Drug of Abuse Panel plus TCA (Triage DOA Panel) rapid drug screening devices were compared at four laboratories. Both assay systems are point of care immunoassays, measuring phencyclidine, barbiturates, amphetamine, cocaine metabolite, methamphetamine, tricyclic antidepressants, opiates, marijuana metabolite, and benzodiazepines in human urine. The performance of these two assay systems, including a cutoff verification and cross-reactivity using spiked urine specimens and accuracy using clinical urine samples, was investigated. The cutoff verification study showed that the Signify ER had 95.4% precision for all drugs tested at concentrations of 50%, 75%, 125%, 150%, and 200% of cutoffs compared to 90% precision obtained with Triage DOA Panel. Accuracy studies testing 53 negative urine samples demonstrated that both Signify ER and Triage DOA Panel have 100% specificity. Testing of 693 positive urine samples demonstrated that Signify ER and Triage DOA Panel have sensitivities of 99.8% and 99.3%, respectively, with an accuracy of 99.9% and 99.6%. A total of 527 compounds were tested for the cross-reactivity study. Eighty-seven structurally related drugs and metabolites were found to cross-react with at least one of the nine tests of the Signify ER. Four hundred forty structurally unrelated compounds that can be found in human urine were shown not to cross-react with the Signify ER. In terms of operating characteristics, the Signify ER device is simpler since only a single pipetting step is required, and reaction completed within 8 min. PMID:12559596

Phillips, Jane Ellen; Bogema, Stuart; Fu, Paul; Furmaga, Wieslaw; Wu, Alan H B; Zic, Vlasta; Hammett-Stabler, Catherine

2003-02-01

396

Chitosan/sulfobutylether-?-cyclodextrin nanoparticles as a potential approach for ocular drug delivery.  

PubMed

Development of efficient ocular delivery nanosystems remains a major challenge to achieve sustained therapeutic effect. The purpose of this work was to develop chitosan nanoparticles using sulfobutylether-?-cyclodextrin (SBE-?-CD) as polyanionic crosslinker and to investigate the potential of using those nanostructures as ocular drug delivery systems. Econazole nitrate (ECO) was chosen as model drug molecule. The influence of different process variables (chitosan molecular weight and the concentration of the two ionic agents) on particle size, polydispersity index, zeta potential, drug content, in vitro release and mucoadhesive properties was investigated. The results showed that the prepared nanoparticles were predominant spherical in shape having average particle diameter from 90 to 673 nm with positive zeta potential values from 22 to 33 mV and drug content values ranging from 13 to 45%. Drug release from optimized nanoparticles was controlled with approximately 50% of the original amount released over a 8h period. The release profile of nanoparticles followed a zero-order release kinetics. The optimized nanoparticles were tested for their use as ocular drug delivery systems on albino rabbits. The in vivo studies revealed that the prepared mucoadhesive nanoparticles had better ability in sustaining the antifungal effect of ECO than the ECO solution. Therefore, chitosan/SBE-?-CD nanoparticles developed showed a promising carrier for controlled delivery of drug to the eye. PMID:21540097

Mahmoud, Azza A; El-Feky, Gina S; Kamel, Rabab; Awad, Ghada E A

2011-07-15

397

Integrating systems biology sources illuminates drug action.  

PubMed

There are significant gaps in our understanding of the pathways by which drugs act. This incomplete knowledge limits our ability to use mechanistic molecular information rationally to repurpose drugs, understand their side effects, and predict their interactions with other drugs. Here, we present DrugRouter, a novel method for generating drug-specific pathways of action by linking target genes, disease genes, and pharmacogenes using gene interaction networks. We construct pathways for more than a hundred drugs and show that the genes included in our pathways (i) co-occur with the query drug in the literature, (ii) significantly overlap or are adjacent to known drug-response pathways, and (iii) are adjacent to genes that are hits in genome-wide association studies assessing drug response. Finally, these computed pathways suggest novel drug-repositioning opportunities (e.g., statins for follicular thyroid cancer), gene-side effect associations, and gene-drug interactions. Thus, DrugRouter generates hypotheses about drug actions using systems biology data. PMID:24577151

Gottlieb, A; Altman, R B

2014-06-01

398

[Effects of flunarizine on positional nystagmus].  

PubMed

The anti-vertigo activity of the flunarizine on the positional nystagmus has been evaluated in 30 subjects suffering from central or peripheral labyrinthine disorders. The medication was given only once at the dose of 10 mg and its activity was evaluated by means of electronystagmographic recording six hours after drug intake. In 9 cases the positional nystagmus, classified according to Nylèn was the first type, in 13 subjects it was the second type and 8 cases had the third type. The drug determined the inhibition of the positional nystagmus in 53% of the subjects and an evident reduction in 27% of the cases. These effects were most evident both in the central lesions and in the I and III type of the positional nystagmus. In the remaining cases (20%) the differences between the nystagmus recorded before and after treatment with flunarizine were not significant. PMID:6626332

Petrone, D; Riondino, R; Fiorella, R

1983-07-30

399

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery  

NASA Astrophysics Data System (ADS)

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

Ensign-Hodges, Laura

400

The Language of Show Biz: A Dictionary.  

ERIC Educational Resources Information Center

This dictionary of the language of show biz provides the layman with definitions and essays on terms and expressions often used in show business. The overall pattern of selection was intended to be more rather than less inclusive, though radio, television, and film terms were deliberately omitted. Lengthy explanations are sometimes used to express…

Sergel, Sherman Louis, Ed.

401

International Plowing Match & Farm Machinery Show  

NSDL National Science Digital Library

The 1995 International Plowing Match & Farm Machinery Show in Ontario, Canada has a site of the Web. The IPM is a non-profit organization of volunteers which annually organizes Canada's largest farm machinery show. The event is commercial and educational. Thousands of school children and educators attend and participate in organized educational activities.

1995-01-01

402

Show Me: Automatic Presentation for Visual Analysis  

Microsoft Academic Search

This paper describes Show Me, an integrated set of user interface commands and defaults that incorporate automatic presentation into a commercial visual analysis system called Tableau. A key aspect of Tableau is VizQL, a language for specifying views, which is used by Show Me to extend automatic presentation to the generation of tables of views (commonly called small multiple displays).

Jock D. Mackinlay; Pat Hanrahan; Chris Stolte

2007-01-01

403

Positive clinical neuroscience: explorations in positive neurology.  

PubMed

Disorders of the brain and its sensory organs have traditionally been associated with deficits in movement, perception, cognition, emotion, and behavior. It is increasingly evident, however, that positive phenomena may also occur in such conditions, with implications for the individual, science, medicine, and for society. This article provides a selective review of such positive phenomena--enhanced function after brain lesions, better-than-normal performance in people with sensory loss, creativity associated with neurological disease, and enhanced performance associated with aging. We propose that, akin to the well-established field of positive psychology and the emerging field of positive clinical psychology, the nascent fields of positive neurology and positive neuropsychology offer new avenues to understand brain-behavior relationships, with both theoretical and therapeutic implications. PMID:23286954

Kapur, Narinder; Cole, Jonathan; Manly, Tom; Viskontas, Indre; Ninteman, Aafke; Hasher, Lynn; Pascual-Leone, Alvaro

2013-08-01

404

[Drug-drug interactions in antirheumatic treatment].  

PubMed

Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

Krüger, K

2012-04-01

405

HIV-Positive Inmates Benefit from Drug Treatment, Study Says  

MedlinePLUS

... The study, published online March 31 in JAMA Internal Medicine , included 882 HIV-infected prisoners in Connecticut who ... maintain these benefits on the outside." SOURCE: JAMA Internal Medicine , news release, March 31, 2014 HealthDay Copyright (c) ...

406

Report Shows Rise in Methamphetamine-Related Hospital Emergency Department Visits  

MedlinePLUS

... Telephone: 240-276-2130 Report shows rise in methamphetamine-related hospital emergency department visits Hospital emergency department ... related to the use of the illicit drug methamphetamine rose from 67,954 in 2007 to 102, ...

407

Recreational Drugs and HIV  

MedlinePLUS

... WITH HIV DRUG USE AND HIV DISEASE DRUG INTERACTIONS THE BOTTOM LINE FOR MORE INFORMATION HOW DOES ... to fight HIV, there can be some serious interactions between drugs and ARVs. These interactions can lead ...

408

Hallucinogens and Dissociative Drugs  

MedlinePLUS

... Get Further Information about Hallucinogens? Glossary References NIDA Publications By Audience By Drug of Abuse By Drug ... of national interest. View all ?Research Reports Featured Publication Drugs, Brains, and Behavior - The Science of Addiction ...

409

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

NASA Astrophysics Data System (ADS)

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

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

410

Balancing motherhood and drug addiction: the transition to parenthood of addicted mothers.  

PubMed

This is a study about balancing motherhood and drug addiction, during the transition to parenthood. Few studies have dealt with the parental experience of drug-addicted mothers. The participants included 24 drug-addicted mothers, on methadone, with ages 25-42 and with children 1-32 months of age. Semi-structured interviews were conducted and analyzed according to Grounded Theory. The mothers' main concern was the ambivalence they felt towards pregnancy/motherhood and drug addiction, which was associated with strong feelings of guilt. Confronted with this ambivalence their maternal role becomes merely functional. They focus on providing the basic care to the child, but show little willingness to talk or play. Social support, especially from the partner seems to have a positive role. PMID:22544158

Silva, Sofia A; Pires, António P; Guerreiro, Cristina; Cardoso, Antónia

2013-03-01

411

Comparison of Weather Shows in Eastern Europe  

NASA Astrophysics Data System (ADS)

Comparison of Weather Shows in Eastern Europe Television weather shows in Eastern Europe have in most cases in the high graphical standard. There is though a wast difference in duration and information content in the weather shows. There are few signs and regularities by which we can see the character of the weather show. The main differences are mainly caused by the income structure of the TV station. Either it is a fully privately funded TV relying on the TV commercials income. Or it is a public service TV station funded mainly by the national budget or fixed fee structure/tax. There are wast differences in duration and even a graphical presentation of the weather. Next important aspect is a supplier of the weather information and /or the processor. Shortly we can say, that when the TV show is produced by the national met office, the TV show consists of more scientific terms, synoptic maps, satellite imagery, etc. If the supplier is the private meteorological company, the weather show is more user-friendly, laical with less scientific terms. We are experiencing a massive shift in public weather knowledge and demand for information. In the past, weather shows consisted only of maps with weather icons. In todaýs world, even the laic weather shows consist partly of numerical weather model outputs - they are of course designed to be understandable and graphically attractive. Outputs of the numerical weather models used to be only a part of daily life of a professional meteorologist, today they are common part of life of regular people. Video samples are a part of this presentation.

Najman, M.

2009-09-01

412

Workplace Drug Testing and Worker Drug Use  

PubMed Central

Objective To examine the nature and extent of the association between workplace drug testing and worker drug use. Data Sources Repeated cross-sections from the 2000 to 2001 National Household Surveys on Drug Abuse (NHSDA) and the 2002 National Survey on Drug Use and Health (NSDUH). Study Design Multivariate logistic regression models of the likelihood of marijuana use are estimated as a function of several different workplace drug policies, including drug testing. Specific questions about penalty severity and the likelihood of detection are used to further evaluate the nature of the association. Principal Findings Individuals whose employers perform drug tests are significantly less likely to report past month marijuana use, even after controlling for a wide array of worker and job characteristics. However, large negative associations are also found for variables indicating whether a firm has drug education, an employee assistance program, or a simple written policy about substance use. Accounting for these other workplace characteristics reduces—but does not eliminate—the testing differential. Frequent testing and severe penalties reduce the likelihood that workers use marijuana. Conclusions Previous studies have interpreted the large negative correlation between workplace drug testing and employee substance use as representing a causal deterrent effect of drug testing. Our results using more comprehensive data suggest that these estimates have been slightly overstated due to omitted variables bias. The overall pattern of results remains largely consistent with the hypothesis that workplace drug testing deters worker drug use.

Carpenter, Christopher S

2007-01-01

413

Drug interactions of lipid-altering drugs.  

PubMed

The use of lipid-altering drugs has been shown to reduce the progression of atherosclerotic lesions and reduce the risk of atherosclerotic events (such as myocardial infarction and stroke). In general, these lipid-altering drugs are well tolerated but there is the potential for drug interactions. For example, HMG-CoA reductase inhibitors may interact with macrolides, azalides, azole antifungals and cyclosporin. Resins (such as cholestyramine and colestipol) may impair the absorption of many concurrent medications. Fibrates have potential drug interactions with warfarin, furosemide (frusemide), oral hypoglycaemics and probenecid. Nicotinic acid (niacin) may have potential drug interactions with high dose aspirin (acetylsalicylic acid), uricosuric agents (such as sulfapyrazone) and alcohol (ethanol). Finally, probucol may have potential drug interactions with antidysrhythmics, tricyclic antidepressants and phenothiazines. In addition, lipid-altering drugs, used in combination, may have the potential for drug interactions, enhancing some of the risks of adverse effects, such as myositis and hepatotoxicity. Therefore, in order to use lipid-altering drugs in the most effective, and safest manner, it is important for the clinician to have an understanding of the mechanisms of potential drug interactions, which drug interactions may theoretically occur, and specifically, which spe cific drug interactions have already been described. PMID:9825949

Bays, H E; Dujovne, C A

1998-11-01

414

Revisiting "the origins of compulsory drug prescriptions".  

PubMed Central

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

Marks, H M

1995-01-01

415

Recovery position - series (image)  

MedlinePLUS

... the victim should be placed in the recovery position. The recovery position helps keep the victim's airway open. To put the victim in the recovery position grab the victim's leg and shoulder and roll ...

416

Wheelchairs, Seating, Positioning  

MedlinePLUS

... Seating, Positioning [+] Text [-] Text print # Resources Wheelchairs, Seating, Positioning Folding Wheelchair - Colours Challenger The common saying is ... must be fitted and prescribed by seating and positioning experts. Cushion - Gel Jay-J2-Recline Seating People ...

417

Benign Paroxysmal Positional Vertigo  

MedlinePLUS

MENU Return to Web version Benign Paroxysmal Positional Vertigo Overview What is benign paroxysmal positional vertigo? Benign paroxysmal positional vertigo (BPPV) is a problem with the nerves and structure ...

418

Monitoring Free Drug Concentration  

Microsoft Academic Search

Measurement of serum drug concentration may be misleading for a strongly protein-bound drug because a drug bound to protein\\u000a is inactive and only unbound or free drug is pharmacologically active. Although free drug concentration can be estimated from\\u000a total concentration in most cases, under certain pathophysiological conditions such as uremia, liver disease, and hypoalbuminemia\\u000a free drug concentration may be significantly

Amitava Dasgupta

419

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

PubMed Central

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

2014-01-01

420

Spacecraft Image Mashup Shows Galactic Collision  

NASA Video Gallery

This new composite image from the Chandra X-ray Observatory, the Hubble Space Telescope, and the Spitzer Space Telescope shows two colliding galaxies more than a 100 million years after they first ...

421

Adult Stem Cell Research Shows Promise  

MedlinePLUS

... Tobacco Products Vaccines, Blood & Biologics Articulos en Espanol Adult Stem Cell Research Shows Promise Search the Consumer Updates Section ... re looking at a particular kind of multipotent adult stem cell—the MSC—which is being used in a ...

422

TRMM Satellite Shows Heavy Rainfall in Cristina  

NASA Video Gallery

NASA's TRMM satellite rainfall data was overlaid on an enhanced visible/infrared image from NOAA's GOES-East satellite showing cloud and rainfall extent. Green areas indicate rainfall at over 20 mm...

423

GOES Satellite Data Shows Tornado Development  

NASA Video Gallery

This animation of NOAA's GOES-East satellite data shows the development and movement of the weather system that spawned tornadoes affecting the southern and eastern U.S. states on April 27-29, 2014...

424

map showing predicted habitat potentional for tortoise  

USGS Multimedia Gallery

This map shows the spatial representation of the predicted habitat potential index values for desert tortoise in the Mojave and parts of the Sonoran Deserts of California, Nevada, Utah, and Arizona. Map: USGS. ...

2009-05-21

425

Projecting future drug expenditures—2005  

Microsoft Academic Search

Purpose. Drug expenditure trends in 2005 and 2006, projected drug expenditures for 2007, and factors likely to infl uence drug costs are discussed. Summary. Various factors are likely to aff ect drug costs, including drug prices, drugs in development, and generic drugs. In 2005, there was a continued moderation of the increase in drug expenditures. Total prescription drug expenditures increased

JAMES M. HOFFMAN; NILAY D. SHAH; LEE C. VERMEULEN; ROBERT J. HUNKLER; KARRIE M. HONTZ

426

Generation and utilization of anti-drug monoclonal antibodies for screening of 36 drug users by dot-ELISA.  

PubMed

In this study, we prepared monoclonal antibodies against morphine, methadone, babital, methamphetamine, and phencyclidine, then developed a dot-ELISA method by such antibodies to test their efficacy in clinical application and the screening of urine samples. It was found that there were 36 narcotics-positive drug users, including 28 morphine positive, six methamphetamine positive, and two positive for both. All the results were confirmed by commercial drug testing kits. PMID:19382846

Wang, Shuang; Wei, Yuzhi; Chen, Guangyu; Liu, Xiaowei; Jin, Haiming; Yan, Zhaoqi; Wu, Qiaowen; Du, Hongwu

2009-04-01

427

Psychological symptoms and drug use severity among Israeli adolescents presenting for outpatient drug abuse treatment  

Microsoft Academic Search

The objective of this study was to assess the rates of externalizing and internalizing symptoms, and the relation between psychological symptoms and drug use severity, among 117 Israeli adolescents presenting for outpatient drug abuse treatment. Psychological symptoms were assessed via both adolescent self-report and parent report. Drug use was assessed using both adolescent self-report and urinalysis. Results showed that 58%

Gary M. Diamond; Miriam C. Izzard; Tami Kedar; Anat Hutlzer; Haim Mell

2005-01-01

428

Drug-Free Zone! Keeping Drugs Out of Your Child's School.  

ERIC Educational Resources Information Center

This book, written for parents of school-aged children and adolescents, shows why drug prevention in most schools today is inadequate, and explains what parents need to do in order to stop the flow of drugs through their local schools. The first half of the book consists of six chapters that explore the problem of drugs in schools. Chapter 1…

Sager, Carol

429

Youth sport programs: an avenue to foster positive youth development  

Microsoft Academic Search

Concern about the growth in adolescent problem behaviours (e.g. delinquency, drug use) has led to increased interest in positive youth development, and a surge in funding for ‘after school programs.’ We evaluate the potential of youth sport programs to foster positive development, while decreasing the risk of problem behaviours. Literature on the positive and negative outcomes of youth sport is

Jessica L. Fraser-Thomas; Jean Côté; Janice Deakin

2005-01-01

430

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

ERIC Educational Resources Information Center

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

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

2013-01-01