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1

Family Checkup: Positive Parenting Prevents Drug Abuse  

MedlinePLUS

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

2

Use of Preventative and Therapeutic Drugs in Show Market Animals  

E-print Network

Various medicines are used in show market livestock and poultry, but exhibitors must ensure that the carcasses do not contain illegal residues of drugs, chemicals and feed additives. Only approved substances should be used. Illegal uses of drugs...

Faries Jr., Floron C.

2001-03-12

3

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

4

Bed Position Matters for Stroke Patients, Report Shows  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Bed Position Matters for Stroke Patients, Report Shows But ... Stroke THURSDAY, Nov. 6, 2014 (HealthDay News) -- Hospital bed positioning can be critical in the first 24 ...

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 (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

7

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

8

Screening Test Finds Drugs That Show Promise Against Ebola  

MedlinePLUS

... Screening Test Finds Drugs That Show Promise Against Ebola Researchers uncover 53 potential treatments; all are already FDA approved but need more ... biocontainment," Garcia-Sastre said. Researchers used this fake Ebola virus ... treatment project, according to background information from the study. ...

9

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

10

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

11

MIT study finds new drug candidate shows promise against cancer  

Cancer.gov

Drugs containing platinum are among the most powerful and widely used cancer drugs. However, such drugs have toxic side effects, and cancer cells can eventually become resistant to them. MIT researchers have now identified, in laboratory studies, a compound that kills cancer cells better than cisplatin, the most commonly used platinum anticancer drug. The new compound may be able to evade cancer-cell resistance to conventional platinum compounds. MIT is home to the David H. Koch Institute for Integrative Cancer Research.

12

New Drug Shows Mixed Results Against Early Alzheimer's  

MedlinePLUS

... In Search of an Alzheimer’s Cure New therapeutic target for Alzheimer’s could lead to drugs without side ... Fitness: Take Care of Your Core Fitness: Get Moving! How Meditation May Help Against Alzheimer’s Reducing Clutter ...

13

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.

14

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.

15

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.

16

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

PubMed Central

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

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

2012-01-01

17

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

Cancer.gov

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

18

UNC study shows potential to revive abandoned cancer drug by nanoparticle drug delivery  

Cancer.gov

Current nanomedicine research has focused on the delivery of established and novel therapeutics. But a UNC team is taking a different approach. They developed nanoparticle carriers to successfully deliver therapeutic doses of a cancer drug that had previously failed clinical development due to pharmacologic challenges. They report their proof of principle findings in the April 30, 2012 early online edition of Proceedings of the National Academy of Sciences.

19

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

MedlinePLUS

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

20

New Drug Regimen Shows Clear Benefit for Treating Advanced Colorectal Cancer  

Cancer.gov

Initial results from a large, randomized clinical trial for patients with advanced colorectal cancer show that those who received a regimen containing the investigational drug oxaliplatin lived months longer than those who received a standard therapy.

21

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.

22

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

PubMed Central

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

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

2014-01-01

23

A luminescent nanoporous hybrid material based drug delivery system showing excellent theranostics potential for cancer.  

PubMed

A novel hybrid nanoporous material (LNH-1) bearing a tris(propyliminomethyl)-phloroglucinol fluorescent moiety in the framework has been designed and administration of an LNH-1 based drug delivery system containing doxorubicin to cancer cells showed inhibition of proliferation, suggesting its future potential theranostics application in cancer. PMID:23872783

Modak, Arindam; Barui, Ayan Kumar; Patra, Chitta Ranjan; Bhaumik, Asim

2013-09-01

24

The effect of methadone maintenance on positive outcomes for opiate injection drug users  

PubMed Central

This study examined outcome variables for 160 opiate injection drug users (IDUs) who entered methadone maintenance between baseline and 6 month follow-up. Outcome variables of interest included drug use, productivity and HIV risk behaviors. Participants were recruited through street outreach in Denver, Colorado from 2000 through 2004 using targeted sampling. The sample was primarily male, 48% White, averaged 39 years of age and had been injecting drugs for an average of nearly 20 years. Significant improvements were found in univariate tests. Logistic regression revealed that spending more time in treatment was a significant predictor of positive outcomes on drug use and HIV risk behaviors. The results underscore the importance of retaining IDUs in methadone maintenance in order to maximize their treatment success. Results from this study show that time in treatment can affect many aspects of the participant’s life in a positive way, including reduction of HIV risk. PMID:19150202

Corsi, Karen F; Lehman, Wayne K; Booth, Robert E

2009-01-01

25

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

E-print Network

Figure 1 Scheme of the longline used in this study. Numbers show hook position. Ramon Munoz was to obtain a simple, statistical relationship between the fishing efficiency of each hook in a basket (a of each hook and in estimating absolute depths. Yoshi- hara (1951) reports that the vertical distributions

26

Report Shows That "Bath Salts" Drugs Were Involved in Nearly 23,000 Emergency Department Visits in One Year  

MedlinePLUS

... Give your feedback today. Report shows that “Bath Salts” drugs were involved in nearly 23,000 emergency ... 2013 A new national report reveals that “bath salts,” a group of drugs containing amphetamine-type stimulants, ...

27

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

PubMed

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

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

2014-08-21

28

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

PubMed

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

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

2014-11-13

29

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.

30

Sca1-positive murine pituitary adenoma cells show tumor growth advantage  

PubMed Central

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

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

2014-01-01

31

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

E-print Network

to the field of mass media through his study of advertisements. He posited that women in advertisements reinforced how women are framed in daily life (Goffman, 1979). As the theory was adapted to journalism (Tuchman, 1978; Gitlin, 1980), such research revealed...” because it focuses on illicit drugs, such as cocaine, heroin, and ecstasy, as the drugs contributing the most to the “drug problem,” while rarely mentioning alcohol and tobacco as part of the problem (Murji, 1998). Therefore, the media conditions “public...

Wood, Michelle

2011-12-31

32

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.

33

Predicting toxicities of reactive metabolite-positive drug candidates.  

PubMed

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

Kalgutkar, Amit S; Dalvie, Deepak

2015-01-01

34

False-positive outcome and drug residue in milk samples over withdrawal times.  

PubMed

This study was conducted to identify false-positive outcomes and drug residues in milk samples over withdrawal times and to determine whether the positive results were caused by drug residues or natural inhibitors. A total of 73 milk samples over withdrawal times after the last intramammary infusion were collected from each treated quarter of cows and tested using the Delvotest SP assay. Reading time was 150, 165, and 180 min, and results of samples were recorded according to the color of the well containing the control milk sample. There were 24, 20, and 12 positive samples at the reading times of 150, 165, and 180 min, respectively. All 24 positive milk samples were heated at 82 degrees C for 5 min and retested to verify that the positive results were caused by drug residues or natural inhibitors. Twenty-one samples that exhibited positive results were negative after heat treatment, and drug residues were not identified by LacTek and Charm tests. However, 3 samples that exhibited positive results from heat treatment of 82 degrees C were positive for drugs. In our study, most positive results (89%) in the milk samples over withdrawal times were false-positive results by natural inhibitors. Moreover, the heat treatment is a fast, simple, and inexpensive method to remove false-positive results and has no effect on positive samples containing drugs. We suggest that heat treatment before screening tests is an effective way to reduce false-positive results in the milk samples. PMID:15738224

Kang, J H; Jin, J H; Kondo, F

2005-03-01

35

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

PubMed Central

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

Lepesheva, Galina I.

2013-01-01

36

False-Positive Outcome and Drug Residue in Milk Samples Over Withdrawal Times  

Microsoft Academic Search

This study was conducted to identify false-positive outcomes and drug residues in milk samples over with- drawal times and to determine whether the positive results were caused by drug residues or natural inhibi- tors. A total of 73 milk samples over withdrawal times after the last intramammary infusion were collected from each treated quarter of cows and tested using the

J. H. Kang; J. H. Jin; F. Kondo

2005-01-01

37

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

Cancer.gov

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

38

Positive family relationships and religious affiliation as mediators between negative environment and illicit drug symptoms in American Indian adolescents.  

PubMed

The present study tests how positive family relationships and religious affiliation mediate between negative familial and social environments, and adolescent illicit drug abuse/dependence symptoms. The theoretical framework is based on an integration of two theories: the ecological model of human development (Bronfenbrenner, 1979) and the social development model (Hawkins & Weis, 1985). We used a stratified random sample of 401 American Indian adolescents. A path analysis tested the integrative theoretical model. Findings showed that positive family relationships mediated the negative impact of addicted family members, violence victimization, and negative school environment on illicit drug abuse/dependence symptoms. Religious affiliation mediated the negative effect of deviant peers on positive family relationships. Intervention and prevention efforts may benefit from promoting positive family relationships and religious affiliation to reduce the impact of complex familial and social problems on illicit drug symptoms. PMID:20359830

Yu, Mansoo; Stiffman, Arlene R

2010-07-01

39

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

Cancer.gov

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

40

Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network.  

PubMed

Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse involves dysphoria, high stress responsiveness and craving. The neurobiology of drug abstinence, however, is poorly understood. We previously identified a unique set of hundred mu-opioid receptor-dependent genes in the extended amygdala, a key site for hedonic and stress processing in the brain. Here we examined these candidate genes either immediately after chronic morphine, nicotine, ?9-tetrahydrocannabinol or alcohol, or following 4 weeks of abstinence. Regulation patterns strongly differed among chronic groups. In contrast, gene regulations strikingly converged in the abstinent groups and revealed unforeseen common adaptations within a novel huntingtin-centered molecular network previously unreported in addiction research. This study demonstrates that, regardless the drug, a specific set of transcriptional regulations develops in the abstinent brain, which possibly contributes to the negative affect characterizing protracted abstinence. This transcriptional signature may represent a hallmark of drug abstinence and a unitary adaptive molecular mechanism in substance abuse disorders. PMID:21955143

Le Merrer, Julie; Befort, Katia; Gardon, Olivier; Filliol, Dominique; Darcq, Emmanuel; Dembele, Doulaye; Becker, Jerome A J; Kieffer, Brigitte L

2012-01-01

41

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

Cancer.gov

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

42

Positively Charged Polyethylenimines Enhance Nasal Absorption of the Negatively Charged Drug, Low Molecular Weight Heparin  

PubMed Central

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 enhancing nasal absorption of LMWH was studied by administering LMWH formulated with PEI into the nose of anesthetized rats and monitoring drug absorption by measuring plasma anti-factor Xa activity. The metabolic stability of LMWH was evaluated by incubating the drug in rat nasal mucosal homogenates. FTIR spectra of the LMWH-PEI formulation showed a shift in peak position compared to LMWH or PEI alone. Decreases in conductivity, zeta potential and the amount of free LMWH in the PEI-LMWH formulation, as revealed by azure A assay, suggest that PEIs possibly neutralize the negative surface charge of LMWH. The efficacy of PEI in enhancing the bioavailability of nasally administered LMWH can be ranked as PEI-1000 KDa ? PEI-750 KDa > PEI-25 KDa. When PEI-1000 KDa was used at a concentration of 0.25%, there was a 4-fold increase in both the absolute and relative bioavailabilities of LMWH compared to the control formulation. Overall, these results indicate that polyethylenimines can be used as potential carriers for nasally administered LMWHs. PMID:17023085

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

2007-01-01

43

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

Cancer.gov

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

44

What do you feel? Adolescent Drug and Alcohol Users Show Altered Brain Response to Pleasant Interoceptive Stimuli*  

PubMed Central

Background Altered interoception, i.e., processing of stimuli from inside the body, has been considered an important component of drug-taking behavior. However, approaches to examine interoceptive sensitivity in humans have been limited. This study examined the hypothesis that adolescents with substance use disorder show altered interoceptive processing, measured by stimulating mechanoreceptive C-fibers (MR-CF) via soft touch. Methods Adolescents with substance use disorders (SUD, n=15) and comparison youth (CON, n=17) underwent functional magnetic resonance imaging (fMRI) during anticipation or reception of a positively valenced “Soft Touch” consisting of MR-CF stimulation to the palm or forearm. Visual analog scales (VAS) indexed subjective interoceptive experience (e.g., pleasantness, intensity). Results Across all conditions, SUD displayed attenuated left posterior insula activation compared to CON . Greater left anterior insula and right lentiform nucleus activation was evident during the application of soft touch for SUD but not for CON. Whereas for CON, greater left anterior insula activation was associated with higher pleasantness ratings, pleasantness was linked to less anterior insula activation in SUD. Finally, within SUD, attenuated posterior insula activation was related to more recent cannabis use. Conclusions SUD adolescents exhibit blunted somatovisceral processing of pleasant stimulation, heightened sensitivity in regions responsible for processing reward value, and altered relationships between interoceptive processing and subjective experience. PMID:24071571

Migliorini, Robyn; Stewart, Jennifer L.; May, April C.; Tapert, Susan F.; Paulus, Martin P.

2013-01-01

45

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

46

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.

47

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

PubMed Central

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

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

2015-01-01

48

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

PubMed Central

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

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

2015-01-01

49

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.

50

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

PubMed

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

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

2014-09-01

51

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. PMID:7599069

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

1995-01-01

52

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

53

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

PubMed Central

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

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

2014-01-01

54

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.

55

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

PubMed Central

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

Hölscher, Christian

2014-01-01

56

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

Microsoft Academic Search

Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent

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

2011-01-01

57

The antitumor drug aclacinomycin A, which inhibits the degradation of ubiquitinated proteins, shows selectivity for the chymotrypsin-like activity of the bovine pituitary 20 S proteasome.  

PubMed

The antitumor drug aclacinomycin A was previously shown to inhibit the degradation of ubiquitinated proteins in rabbit reticulocyte lysates with an IC50 of 52 microM (Isoe, T., Naito, M., Shirai, A., Hirai, R., and Tsuruo, T.(1992) Biochim. Biophys. Acta 1117, 131-135). We report here that from all the catalytic activities of the 20 S proteasome tested, the chymotrypsin-like activity was the only one affected by the antitumor drug. An important requirement for inhibition of the chymotrypsin-like activity seemed to be the presence of hydrophobic nonpolar residues in positions P1 to P3. Degradation of Z-E(OtBu)AL-pNA and Z-LLL-AMC at pH 7.5 was dramatically (87-98%) inhibited by 50 microM of the drug, while that of Z-GGL-pNA (containing uncharged polar residues in positions P2 and P3) and succinyl-LLVY-AMC (containing an uncharged polar residue in the P1 position) was inhibited only 11 and 24%, respectively. Aclacinomycin A had no effect on cathepsin B, stimulated trypsin, and inhibited chymotrypsin and, to a lesser extent, calpain. The aglycone and sugar moieties of the cytotoxic drug are essential for inhibition. The results presented here support a major role for the chymotrypsin-like activity in the degradation of ubiquitinated proteins. Aclacinomycin A is the first described non-peptidic inhibitor showing discrete selectivity for the chymotrypsin-like activity of the 20 S proteasome. PMID:8663210

Figueiredo-Pereira, M E; Chen, W E; Li, J; Johdo, O

1996-07-12

58

Eczematous-type multiple drug allergy from isoniazid and ethambutol with positive patch test results.  

PubMed

Multiple drug allergy (MDA) is characterized by hypersensitivity to 2 or more chemically unrelated drugs. Multiple drug allergy from simultaneous use of antituberculosis drugs is a rare phenomenon that mainly presents as an urticarial or maculopapular eruption. This case report describes a 58-year-old man who developed a generalized eczematous eruption during the sixth week of oral therapy with 4 antituberculosis drugs-isoniazid, ethambutol, rifampicin, and morphazinamide-for treatment of suspected pleural tuberculosis. The eruption resolved after treatment with systemic corticosteroids and cessation of isoniazid and ethambutol. During a lesion-free period 6 months after cessation of the corticosteroids, patch testing with serial dilutions of isoniazid and ethambutol revealed positive reactions; irritant patch test reactions were excluded by testing with graded concentrations of each drug. The patient avoided the causative drugs and reported no new eruptions at 1-year follow-up. It is important for dermatologists to consider the value of patch testing in determining the causative drugs in suspected cases of eczematous-type MDA. PMID:24153138

Özkaya, Esen

2013-09-01

59

Virginia Tech Department of Chemistry Faculty Position in Organic Chemistry (Drug Discovery)  

E-print Network

Virginia Tech Department of Chemistry Faculty Position in Organic Chemistry (Drug Discovery) The Department of Chemistry announces a tenure-track opening in the area of Organic Chemistry at the Assistant, or the discovery of biologically active naturally-occurring compounds. Applicants must have a Ph.D. in chemistry

Virginia Tech

60

HIV-1 drug resistance mutations among infants born to HIV-positive mothers in Busia, Kenya.  

PubMed

To determine HIV-1 subtypes and transmitted HIV-1 drug-resistant mutations among HIV-1-positive children born to HIV-positive mothers in Busia County, blood samples were collected from 53 children aged between 6 weeks and 5 years in 2011. Their mothers were HIV-1 positive and on antiretroviral therapy at the time the children were born. The samples were analyzed for HIV-1 drug resistance and subtypes through sequencing of portions of the HIV-1 pol gene. The generated sequences were analyzed for subtype diversity using the REGA and BLAST subtyping tools. HIV-1 drug resistance was determined using the Stanford University HIV database. Of the 53 samples that were successfully amplified and sequenced, 69.8% (37/53) were determined to be HIV-1 subtype A, 22.6% (12/53) were subtype D, 5.6% (3/53) were subtype C, and 1.8% (1/53) were subtype A1C. The prevalence of HIV-1 drug resistance mutations of any kind was 22.6% (12/53). PMID:25171915

Lel, Rency; Ngaira, Jane; Lihana, Raphael; Khamadi, Samoel

2014-12-01

61

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

PubMed

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

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

2014-11-01

62

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

PubMed

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

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

2014-09-01

63

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

PubMed

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

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

2014-10-01

64

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

PubMed Central

Objective We screened commonly used prescription drugs for possible carcinogenic effects. Methods In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p? 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. Results There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. Conclusions These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine. PMID:19582585

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

2010-01-01

65

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

PubMed

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

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

2013-08-01

66

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

PubMed Central

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

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

2013-01-01

67

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

PubMed

The objective of this study was to examine C57BL/6J (B6) mice during extinction conditions, after food training, and for rates and patterns of operant behavior that seems similar to behavior maintained by intravenous cocaine injections. The rationale was to evaluate the potential for false positives in the intravenous self-administration test using protocols common in studies of knockout mice backcrossed to B6. An additional aim was to assess the influence of food-associated and drug-associated cues and mouse strain. Mice were allowed to acquire lever pressing reinforced by sweetened condensed milk under a fixed ratio 1 then fixed ratio 2 schedule of reinforcement accompanied by a flashing light. A catheter base was then implanted for simulation of intravenous 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 criterion for positive results in the intravenous drug self-administration test include an increase in responding when cocaine is made available after extinction with saline self-administration. PMID:21522054

Thomsen, Morgane; Caine, S Barak

2011-06-01

68

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

PubMed Central

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

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

2012-01-01

69

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

PubMed Central

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

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

2014-01-01

70

Behavioral phenotyping of heterozygous acetylcholinesterase knockout (AChE+/-) mice showed no memory enhancement but hyposensitivity to amnesic drugs.  

PubMed

Decrease in the expression or activity of acetylcholinesterase (AChE) enzymatic activity results in increased cholinergic tonus in the brain and periphery, with concomitant regulations of nicotinic and muscarinic receptors expression. We generated AChE knockout mice and characterized the behavioral phenotype of heterozygous animals, focusing on learning and memory functions. Male and female, AChE+/- and AChE+/+ littermate controls (129 sv strain) were tested at 5-9 weeks of age. AChE activity was significantly decreased in the hippocampus and cortex of AChE+/- mice, but butyrylcholinesterase activity was preserved. AChE+/- mice failed to show any difference in terms of locomotion, exploration and anxiety parameters in the open-field test. Animals were then tested for place learning in the water-maze. They were trained using a 'sustained acquisition' protocol (3 swim trials per day) or a 'mild acquisition' protocol (2 swim trials per day) to locate an invisible platform in fixed position (reference memory procedure). Then, during 3 days, they were trained to locate the platform in a variable position (working memory procedure). Learning profiles and probe test performances were similar for AChE+/- and AChE+/+ mice. Mice were then treated with the muscarinic receptor antagonist scopolamine (0.5, 5 mg/kg) 20 min before each training session. Scopolamine impaired learning at both doses in AChE+/+ mice, but only at the highest dose in AChE+/- mice. Moreover, the intracerebroventricular injection of amyloid-beta25-35 peptide, 9 nmol, 7 days before water-maze acquisition, failed to induce learning deficits in AChE+/- mice, but impaired learning in AChE+/+ controls. The peptide failed to be toxic in forebrain structures of AChE+/- mice, since an increase in lipid peroxidation levels was measured in the hippocampus of AChE+/+ but not AChE+/- mice. We conclude that the increase in cholinergic tonus observed in AChE+/- mice did not result in increased memory functions but allowed a significant prevention of the deleterious effects of muscarinic blockade or amyloid toxicity. PMID:19766675

Espallergues, Julie; Galvan, Laurie; Sabatier, Florence; Rana-Poussine, Vanessa; Maurice, Tangui; Chatonnet, Arnaud

2010-01-20

71

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. PMID:23995135

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

72

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

ERIC Educational Resources Information Center

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

Copeland, Lorraine

2004-01-01

73

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

PubMed

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

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

2015-03-01

74

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

PubMed Central

The task of finding selective and stable peptide receptor agonists with low molecular weight, desirable pharmacokinetic properties and penetrable to the blood-brain barrier has proven too difficult for many highly coveted drug targets, including receptors for endothelin, vasoactive intestinal peptide and galanin. These receptors and ligand-gated ion channels activated by structurally simple agonists such as glutamate, glycine and GABA present such a narrow chemical space that the design of subtype-selective molecules capable of distinguishing a dozen of glutamate and GABA receptor subtypes and possessing desirable pharmacokinetic properties has also been problematic. In contrast, the pharmaceutical industry demonstrates a remarkable success in developing 1,4-benzodiazepines, positive allosteric modulators (PMAs) of the GABAA receptor. They were synthesized over 50 years ago and discovered to have anxiolytic potential through an in vivo assay. As exemplified by Librium, Valium and Dormicum, these allosteric ligands of the receptor became the world's first blockbuster drugs. Through molecular manipulation over the past 2 decades, including mutations and knockouts of the endogenous ligands or their receptors, and by in-depth physiological and pharmacological studies, more peptide and glutamate receptors have become well-validated drug targets for which an agonist is sought. In such cases, the pursuit for PAMs has also intensified, and a working paradigm to identify drug candidates that are designed as PAMs has emerged. This review, which focuses on the general principles of finding PAMs of peptide receptors in the 21st century, describes the workflow and some of its resulting compounds such as PAMs of galanin receptor 2 that act as potent anticonvulsant agents. PMID:23624758

Bartfai, Tamas; Wang, Ming-wei

2013-01-01

75

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

PubMed Central

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

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

2014-01-01

76

Spatial analysis of HIV positive injection drug users in San Francisco, 1987 to 2005.  

PubMed

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

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

2014-04-01

77

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

78

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

PubMed Central

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

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

2015-01-01

79

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

PubMed

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

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

2014-12-01

80

The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target  

PubMed Central

The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD+ bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD+ and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against T. gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1?M. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there maybe significant off target effects for this family of inhibitors. PMID:24398298

Wilkinson, Craig; McPhillie, Martin J.; Zhou, Ying; Woods, Stuart; Afanador, Gustavo A.; Rawson, Shaun; Khaliq, Farzana; Prigge, Sean T.; Roberts, Craig W.; Rice, David W.; McLeod, Rima; Fishwick, Colin W.; Muench, Stephen P.

2014-01-01

81

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

PubMed Central

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

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

2009-01-01

82

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

PubMed Central

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

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

2015-01-01

83

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

Code of Federal Regulations, 2010 CFR

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

2010-10-01

84

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

PubMed Central

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

Lee, Tak Yan

2011-01-01

85

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

86

Ado-trastuzumab Emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer.  

PubMed

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the antitumor properties of the humanized anti-human epidermal growth factor receptor 2 (HER2) antibody, trastuzumab, with the maytansinoid, DM1, a potent microtubule-disrupting agent, joined by a stable linker. Upon binding to HER2, the conjugate is internalized via receptor-mediated endocytosis, and an active derivative of DM1 is subsequently released by proteolytic degradation of the antibody moiety within the lysosome. Initial clinical evaluation led to a phase III trial in advanced HER2-positive breast cancer patients who had relapsed after prior treatment with trastuzumab and a taxane, which showed that T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine. In 2013, T-DM1 received FDA approval for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane, separately or in combination, the first ADC to receive full approval based on a randomized study. PMID:24967516

Lambert, John M; Chari, Ravi V J

2014-08-28

87

Herceptin now approved in the EU for patients with HER2-positive advanced stomach cancer First targeted biological therapy to show survival benefit in stomach cancer  

Microsoft Academic Search

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Commission has approved Herceptin (trastuzumab) in combination with chemotherapy for use in patients with HER2-positive metastatic stomach (gastric) cancer. The approval is based on the impressive results from the international ToGA trial, which showed that treatment with Herceptin significantly prolongs the lives of patients with this aggressive cancer. Overall

F. Hoffmann-La

88

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

89

Illicit drug use, alcohol use and nicotine dependence as predictors of antiretroviral adherence in a sample of HIV positive smokers  

Microsoft Academic Search

Objective. Predictors of non-adherence to antiretroviral medications in a population of low-income, multiethnic, HIV-positive smokers were investigated. ^ Methods. A secondary analysis was conducted using baseline data collected from 326 patients currently prescribed antiretrovirals enrolled in a randomized clinical trial assessing smoking outcomes. Variables evaluated included demographics, stress, depression, nicotine dependence, illicit drug use and alcohol use. ^ Results. The

Rachel M Marks

2010-01-01

90

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

PubMed

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

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

2014-05-01

91

A case of HER2-positive male breast cancer with lung metastases showing a good response to trastuzumab and paclitaxel treatment  

Microsoft Academic Search

We present a case of advanced HER2-positive male breast cancer, which showed a good response to a combined treatment of trastuzumab\\u000a and paclitaxel. A 78-year-old man was diagnosed with invasive ductal carcinoma (T4d N3 M1, stage IV). He had advanced breast\\u000a cancer consisting of multiple tumors with skin involvement and redness over the entire left chest region. A computed tomography

Hironori Hayashi; Mariko Kimura; Nobuyasu Yoshimoto; Masanori Tsuzuki; Nobuyuki Tsunoda; Takashi Fujita; Toshinari Yamashita; Hiroji Iwata

2009-01-01

92

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

PubMed

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

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

2015-02-15

93

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

SciTech Connect

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

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

2013-10-15

94

[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 (18F), 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

95

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

Code of Federal Regulations, 2011 CFR

...submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655...submit to a test, verified positive drug test result and/or breath alcohol test result of...

2011-10-01

96

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

Code of Federal Regulations, 2010 CFR

...submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655...submit to a test, verified positive drug test result and/or breath alcohol test result of...

2010-10-01

97

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. PMID:20056691

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

2010-01-01

98

Unprotected Sexual Behavior Among Heterosexual HIV-Positive Injection Drug Using Men: Associations by Partner Type and Partner Serostatus  

PubMed Central

Few studies have examined sexual risk behaviors of HIV-positive, heterosexual, injection drug using (IDU) men. We investigated such behaviors and associations with risk among sexually active, HIV-positive IDU men who reported only female sex partners in the 3 months prior to baseline interview. We examined associations separately for four non-exclusive groups of men by crossing partner type (main or casual) and partner serostatus (HIV-positive or HIV-negative/unknown). Of 732 male participants, 469 (64%) were sexually active with only female partners. Of these 469 men, 155 (33%) reported sex with HIV-positive main partners, 127 (27%) with HIV-negative or unknown serostatus main partners, 145 (31%) with HIV-positive casual partners, and 192 (41%) with HIV-negative/unknown serostatus casual partners. Significant multivariate associations for unprotected sex with HIV-negative or unknown serostatus main partners were less self-efficacy to use condoms, weaker partner norms supporting condoms, and more negative condom beliefs. Similar correlates were found for unprotected sex with HIV-positive main and casual partners. In addition, alcohol or drug use during sex was a significant correlate of unprotected sex with HIV-positive main partners, while depression was significant for HIV-positive casual partners. For unprotected sex with HIV-negative/unknown status casual partners, self-efficacy for condom use, sex trade, and education were significant multivariate correlates. A combination of broad and tailored intervention strategies based on the relationship pattern of men's lives may provide the most benefit for reducing unprotected sex with female partners. PMID:16736116

Mizuno, Yuko; Metsch, Lisa R.; Garfein, Richard; Tobin, Karin; Knight, Kelly; Latka, Mary H.

2006-01-01

99

Drugs that have been shown to cause drug-induced immune hemolytic anemia or positive direct antiglobulin tests: some interesting findings since 2007.  

PubMed

This review updates new findings in drug-induced immune- hemolytic anemia (DIIHA) since the 2007 review in Immunohematology by these authors. Twelve additional drugs have been added to the three tables listing drugs associated with drug-dependent antibodies, drugs associated with drug-independent antibodies, and drugs associated with nonimmunologic protein adsorption. Other updated findings include (1) piperacillin is currently the most commonly encountered cause of DIIHA, (2) new data on blood group specificity of drug-dependent antibodies, (3) drug-dependent antibodies detected in healthy donors, (4) DIIHA associated with transplantation, and(5) DIIHA associated with chemotherapeutic drugs. PMID:25247621

Garratty, George; Arndt, Patricia A

2014-01-01

100

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

101

The antispasmodic drug mebeverine leads to positive amphetamine results by fluorescence polarization immunoassay (FPIA)--studies on the toxicological analysis of urine by FPIA and GC-MS.  

PubMed

Mebeverine (Duspatal, MB), an antispasmodic drug, is the veratric acid ester of 4-[ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino]butan-1-ol (MB-OH), which is a N-substituted ethylamphetamine derivative. MB is metabolized via ester hydrolysis to MB alcohol (MB-OH) and veratric acid. N-Dehydroxybutylation leads to methoxyethylamphetamine (MO-EA) and, after O-demethylation, to hydroxy EA (HO-EA). N-Bisdealkylation leads to p-methoxyamphetamine (PMA). MO-EA and PMA are also known as designer drugs. Fluorescence polarization immunoassay (FPIA) and gas chromatographic-mass spectrometric studies on the toxicological analysis of MB after ingestion of a single 405-mg oral dose of MB were performed. We could show that intake of MB leads to positive FPIA results for amphetamine. The N-dehydroxybutyl metabolites of MB, MO-EA, HO-EA, and the bis-dealkyl metabolite PMA should be responsible for the positive immunoassay results. Using our systematic toxicological analysis procedure, every positive amphetamine immunoassay could be explained by detection of MO-EA, HO-EA, and/or PMA. Misinterpretation of the origin of MO-EA, HO-EA, or PMA can be avoided by detecting the specific (non-dehydroxybutylated) metabolites of MB, which are excreted for a much longer time after ingestion. PMID:11499887

Kraemer, T; Wennig, R; Maurer, H H

2001-01-01

102

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

PubMed

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

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

2015-02-01

103

Are phylogenetic position, virulence, drug susceptibility and in vivo response to treatment in mycobacteria interrelated?  

PubMed

Phylogenetic analyses on the basis of multiple house-keeping genes and whole genome sequences have offered new insights in the phylogeny of the genus Mycobacterium. This genus yields obligate pathogens, the M. tuberculosis complex and M. leprae, as well as opportunistic pathogens (e.g. M. avium, M. intracellulare, M. kansasii, M. marinum, M. malmoense) and saprophytes (e.g. M. phlei, M. sphagni, M. gordonae). The most virulent mycobacteria, the M. tuberculosis complex, M. leprae and the M. kansasii-M. szulgai-M. marinum-M. ulcerans group are phylogenetically related and infections by these organisms are better treatable than those caused by less virulent and phylogenetically more distantly related Mycobacterium species. The most virulent Mycobacterium species are also characterized by high levels of natural drug susceptibility. In this paper, we review studies of phylogeny, drug susceptibility, and clinical significance to support our hypothesis that drug susceptibility in mycobacteria is acquired and reflects the low level of competition in -and adaptation to- a closer-to-human (environmental) niche. In turn, mycobacteria that inhabit the most competitive environmental niches are the least adapted to humans, thus of low clinical significance, but most tolerant to antibiotics derived from microbes with which they share their habitat, lowering the chances of cure in case of infection. PMID:22036704

van Ingen, Jakko; Boeree, Martin J; van Soolingen, Dick; Iseman, Michael D; Heifets, Leonid B; Daley, Charles L

2012-06-01

104

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

PubMed Central

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

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

2014-01-01

105

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

PubMed

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

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

2014-11-11

106

High Rate of Non-detectable HIV-1 RNA Among Antiretroviral Drug Naive HIV Positive Individuals in Nigeria  

PubMed Central

Plasma HIV-1 RNA concentration, or viral load, is an indication of the magnitude of virus replication and largely correlates with disease progression in an infected person. It is a very useful guide for initiation of therapy and monitoring of response to antiretroviral drugs. Although the majority of patients who are not on antiretroviral therapy (ART) have a high viral load, a small proportion of ART naive patients are known to maintain low levels or even undetectable viral load levels. In this study, we determined the rate of undetectable HIV-1 RNA among ART naive HIV positive patients who presented for treatment at the University College Hospital (UCH), Ibadan, Nigeria from 2005 to 2011. Baseline viral load and CD4 lymphocyte cell counts of 14,662 HIV positive drug naive individuals were determined using the Roche Amplicor version 1.5 and Partec easy count kit, respectively. The detection limits of the viral load assay are 400 copies/mL and 750,000 copies/mL for lower and upper levels, respectively. A total of 1,399 of the 14,662 (9.5%) HIV-1 positive drug naive individuals had undetectable viral load during the study period. In addition, the rate of non-detectable viral load increased over the years. The mean CD4 counts among HIV-1 infected individuals with detectable viral load (266 cells/?L; range = 1 to 2,699 cells/?L) was lower than in patients with undetectable viral load (557 cells/?L; range = 1 to 3,102 cells/?L). About 10% of HIV-1 infected persons in our study population had undetectable viral load using the Roche Amplicor version 1.5. PMID:25512693

Odaibo, Georgina N; Adewole, Isaac F; Olaleye, David O

2013-01-01

107

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

E-print Network

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

Pillow, Jonathan

108

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

PubMed Central

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

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

2009-01-01

109

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. PMID:24834351

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

2014-01-01

110

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

PubMed Central

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

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

2010-01-01

111

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

112

Inhibition of anion and glucose permeabilities by anesthetics in erythrocytes. The mechanisms of action of positively and negatively charged drugs.  

PubMed

(1) The mode of action of anesthetics as inhibitors of Cl- and glucose transports in human red cells was studied. The term anesthetic is taken in its broad meaning as defined by Seeman (Seeman, P. (1972) Pharmacol. Rev. 24, 583-655) and covers anionic and cationic liposoluble compounds which reversibly block the rising phase of the action potential, without effect on the resting membrane potential. (2) Phenothiazine derivatives were chosen as prototypes of anesthetics because they represent a set of compounds having the same basic chemical structure, the phenothiazine ring, but with either a positive or a negative charge. (3) The Cl- self-exchange is inhibited by both cationic and anionic derivatives. However, to obtain the same level of inhibition, it is necessary to use a concentration 10-100 times higher with cationic than with anionic drugs. (4) At a concentration which inhibits Cl- permeability, cationic derivatives induce a very strong morphological change (cup-shaped cells: stomatocytes or spherostomatocytes) and protect erythrocytes against osmotic hemolysis, signifying that the membrane is fully expanded. Conversely, with anionic derivatives, inhibition occurs at a concentration which does not induce any apparent shape change or protect against osmotic hemolysis: there is no significant membrane expansion. (5) Glucose permeability, measured by glucose exit, is inhibited by cationic and anionic phenothiazine, but always at a concentration which fully expands the membrane as indicated by morphological changes and anti-hemolytic effects. It is interesting to point out that whilst glucose exit shows inhibition by cationic derivatives, glucose exchange flux is scarcely altered. (6) It is concluded that cationic and anionic anesthetics are general inhibitors of transmembrane solute movements involving a facilitated-diffusion process. However, the mechanism of inhibition is not identical for all: inhibition of glucose permeability by anionic and cationic anesthetics, as well as inhibition of Cl- permeability by cationic anesthetics may be of a non-specific nature and result from their interaction with the bilayer (this indirect effect is discussed); on the other hand, inhibition of Cl- permeability by anionic anesthetics may result from a specific perturbation of the transport mechanism according to recent evidence in some cases (Cousin, J.L. and Motais, R. (1979) J. Membrane Biol. 46, 125-153; Zaki, L., Ruffing, W. Gärtner, E.M., Fasold, H., Motais, R. and Passow, H. (1977) 11th FEBS Meeting, Copenhagen, A4 17-671. PMID:6105880

Motais, R; Baroin, A; Motais, A; Baldy, S

1980-07-01

113

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

PubMed Central

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

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

2011-01-01

114

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

PubMed

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

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

2013-04-17

115

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

116

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

E-print Network

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

Nizet, Victor

117

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

118

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

PubMed Central

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

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

2014-01-01

119

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

120

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

PubMed

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

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

2015-01-01

121

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

PubMed Central

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

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

2013-01-01

122

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

PubMed Central

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

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

2014-01-01

123

Mutation at Positively Selected Positions in the Binding site for HLA-C Shows KIR2DL1 is a More Refined but Less Adaptable NK cell Receptor than KIR2DL31  

PubMed Central

Through recognition of HLA class I, killer cell immunoglobulin-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 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 can 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 fits 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, Ana; Moesta, Achim K.; Graef, Thorsten; Abi Rached, Laurent; Norman, Paul J.; Guethlein, Lisbeth A.; Fleischhauer, Katharina; Parham, Peter

2012-01-01

124

A randomized clinical trial of a manual-guided risk reduction intervention for HIV-positive injection drug users.  

PubMed

This study randomized 90 HIV-seropositive, methadone-maintained injection drug users (IDUs) to an HIV Harm Reduction Program (HHRP+) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project. The treatment phase lasted 6 months, with follow-ups at 6 and 9 months after treatment entry. Patients in both treatments showed reductions in risk behaviors. However, patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment; at follow-up, they had lower addiction severity scores and were less likely to have engaged in high risk behavior. Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors. PMID:12683743

Margolin, Arthur; Avants, S Kelly; Warburton, Lara A; Hawkins, Keith A; Shi, Julia

2003-03-01

125

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

126

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

PubMed Central

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

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

2012-01-01

127

Injecting drug use is associated with a more rapid CD4 cell decline among treatment naïve HIV-positive patients in Indonesia  

PubMed Central

Background It remains unclear whether the natural course of human immunodeficiency virus (HIV) differs in subjects infected through injecting drug use (IDU) and no data have been published from low- or middle-income countries. We addressed this question in an urban cohort in Indonesia, which is experiencing a rapidly growing HIV epidemic strongly driven by IDU. Methods All antiretroviral treatment (ART) naïve HIV-positive patients who had at least two subsequent CD4 cell counts available before starting ART were included in this study. We examined the association between IDU and CD4 cell decline using a linear mixed model, with adjustment for possible confounders such as HIV viral load and hepatitis C antibodies. Results Among 284 HIV-positive ART naïve patients, the majority were male (56%) with a history of IDU (79% among men). People with a history of IDU had a statistically significant faster decline in CD4 cells (p<0.001). Based on our data, patients with a history of IDU would have an average 33% decline in CD4 cells after one year without ART, compared with a 22% decline among non-users. At two years, the decline would average 66 and 40%, respectively. No other factor was significantly associated with CD4 cell decline. Conclusions We show that a history of IDU is associated with a more rapid CD4 cell natural decline among HIV-positive individuals in Indonesia. These findings have implications for monitoring ART naïve patients with a history of IDU and for starting ART in this group. PMID:24388495

Meijerink, Hinta; Wisaksana, Rudi; Iskandar, Shelly; den Heijer, Martin; van der Ven, Andre J A M; Alisjahbana, Bachti; van Crevel, Reinout

2014-01-01

128

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

SciTech Connect

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

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

2009-05-20

129

DIETARY INTAKE AND BODY MASS INDEX IN HIV-POSITIVE AND HIV-NEGATIVE DRUG ABUSERS OF HISPANIC ETHNICITY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Malnutrition in drug abusers has been attributed to poor diet. However, previous studies are conflicting. Many studies have not considered possible concurrent HIV disease. The purpose of this study was to determine the relationship between drug abuse and dietary intake in Hispanic Americans with and...

130

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

Microsoft Academic Search

Background  Few investigations have assessed risk behaviours and social-structural contexts of risk among injecting drug users (IDUs)\\u000a in Northeast India, where injecting drug use is the major route of HIV transmission. Investigations of risk environments are\\u000a needed to inform development of effective risk reduction interventions.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  This mixed methods study of HIV-positive IDUs in Manipur included a structured survey (n = 75),

Venkatesan Chakrapani; Peter A Newman; Murali Shunmugam; Robert Dubrow

2011-01-01

131

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

PubMed

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

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

2015-02-01

132

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

PubMed Central

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

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

2014-01-01

133

Ebola Drug Shows Promise in Monkey Trial  

MedlinePLUS

... that we can protect non-human primates from Ebola virus, using only a single . . . agent," study lead author ... of VP24 alone is enough to protect against Ebola virus infection, and that targeting VP24 may lead to ...

134

HER2-positive gastric cancer showing marked thickening of the gastric wall on ultrasonographic and computed tomographic scans. a chance phenomenon or a specific behaviour of this cancer type? Report of three cases.  

PubMed

Worldwide, gastric cancer is the fourth most commonly diagnosed type of cancer and the second most common cause of cancer-related death. Recently, it was demonstrated that 15-20% of advanced gastro-oesophageal carcinomas overexpress human epidermal receptor 2 (HER2), one of a family of four identified human epidermal receptors. As in HER2-positive breast cancer, trastuzumab, a monoclonal antibody targeting HER2 receptor, with chemotherapy improves prognosis, time-to-progression and overall survival in patients with advanced gastric cancer. Computed tomography (CT) and ultrasound (US) imaging of gastric cancer has been previously reported, however, to our knowledge HER2-positive gastric adenocarcinoma appearance on US and CT scans has not been previously described and no CT and US images of this variant of adenocarcinoma have been found. We herein report three cases of patients with HER2-positive gastric cancer that showed a marked thickening of the gastric wall on US and CT examination. PMID:25202095

DI Cicilia, Roberto; Mordenti, Patrizia; Anselmi, Elisa; Paties, Carlo; Carella, Egidio; Cavanna, Luigi

2014-09-01

135

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

PubMed Central

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

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

2014-01-01

136

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

137

Acupuncture and Spirituality-Focused Group Therapy for the Treatment of HIV-Positive Drug Users: A Preliminary Study  

Microsoft Academic Search

In this study, 40 HIV-seropositive, cocaine abusing, methadone maintained drug users were randomized to either the standard five-needle National Acupuncture Detoxification Association (NADA) protocol or to a reduced, escalating dose (one to three needle) protocol. In addition to receiving their assigned acupuncture treatments, the last 15 patients also received a spirituality-focused group therapy intervention. Acupuncture treatments were offered five days

Arthur Margolin; S. Kelly Avants; Ruth Arnold

2005-01-01

138

Drug repurposing based on drug-drug interaction.  

PubMed

Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10 835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. PMID:24934184

Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

2015-02-01

139

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

Microsoft Academic Search

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

Joseph T Hanlon; Catherine I Lindblad; Shelly L Gray

2004-01-01

140

On the Stability of Pt(IV) Pro-Drugs with Haloacetato Ligands in the Axial Positions.  

PubMed

The design of Pt(IV) pro-drugs as anticancer agents is predicated on the assumption that they will not undergo substitution reactions before entering the cancer cell. Attempts to improve the cytotoxic properties of Pt(IV) pro-drugs included the use of haloacetato axial ligands. Herein, we demonstrate that Pt(IV) complexes with trifluoroacetato (TFA) or dichloroacetato (DCA) ligands can be unstable under biologically relevant conditions and readily undergo hydrolysis, which results in the loss of the axial TFA or DCA ligands. The half-lives for Pt(IV) complexes with two TFA or DCA ligands at pH?7 and 37?°C range from 6 to 800?min, which is short relative to the duration of cytotoxicity experiments that last 24-96?h. However, complexes with two monochloroacetato (MCA) or acetato axial ligands are stable under biologically relevant conditions. The loss of the axial ligands depends primarily on the electron-withdrawing strength of the axial ligands, but also upon the nature of the equatorial ligands. We were unable to find obvious correlations between the structures of the Pt(IV) complexes and the rates of decay of the parent compounds. The X-ray crystal structures of the bis-DCA and bis-MCA Pt(IV) derivatives of oxaliplatin did not reveal any significant structural differences that could explain the observed differences in stability. PMID:25529335

Wexselblatt, Ezequiel; Raveendran, Raji; Salameh, Sawsan; Friedman-Ezra, Aviva; Yavin, Eylon; Gibson, Dan

2015-02-01

141

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). PMID:22889235

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

2012-01-01

142

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

PubMed Central

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

Cheng, Kejun; Rice, Kenner C.

2013-01-01

143

Target-independent prediction of drug synergies using only drug lipophilicity.  

PubMed

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

Yilancioglu, Kaan; Weinstein, Zohar B; Meydan, Cem; Akhmetov, Azat; Toprak, Isil; Durmaz, Arda; Iossifov, Ivan; Kazan, Hilal; Roth, Frederick P; Cokol, Murat

2014-08-25

144

The interval between initiation of anti-tuberculosis treatment in patients with culture-positive pulmonary tuberculosis and receipt of drug-susceptibility test results.  

PubMed

Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media. PMID:17297247

Joh, Joon-Sung; Lee, Chang Hoon; Lee, Ji Eun; Park, Young-Kil; Bai, Gill-Han; Kim, Eui-Chong; Han, Sung Koo; Shim, Young-Soo; Yim, Jae-Joon

2007-02-01

145

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

PubMed Central

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

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

2014-01-01

146

Prevalence of sexually acquired antiretroviral drug resistance in a community sample of HIV-positive men who have sex with men in New York City.  

PubMed

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

Goldsamt, Lloyd A; Clatts, Michael C; Parker, Monica M; Colon, Vivian; Hallack, Renee; Messina, Maria G

2011-05-01

147

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

PubMed Central

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

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

2011-01-01

148

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

PubMed

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

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

2011-12-01

149

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. PMID:21104390

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

2011-01-01

150

Drug addiction.  

PubMed

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 CB(1) antagonist/inverse agonist rimonabant has been shown to reduce the behavioral effects of stimuli associated with drugs of abuse, including nicotine, alcohol, cocaine, and marijuana. Thus, the endocannabinoid system represents a promising target for development of new treatments for drug addiction. PMID:21104390

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

2009-01-01

151

TraA and its N-terminal relaxase domain of the Gram-positive plasmid pIP501 show specific oriT binding and behave as dimers in solution  

PubMed Central

TraA is the DNA relaxase encoded by the broad-host-range Grampositive plasmid pIP501. It is the second relaxase to be characterized from plasmids originating from Gram-positive organisms. Full-length TraA (654 amino acids) and the N-terminal domain (246 amino acids), termed TraAN246, were expressed as 6×His-tagged fusions and purified. Small-angle X-ray scattering and chemical cross-linking proved that TraAN246 and TraA form dimers in solution. Both proteins revealed oriTpIP501 (origin of transfer of pIP501) cleavage activity on supercoiled plasmid DNA in vitro. oriT binding was demonstrated by electrophoretic mobility shift assays. Radiolabelled oligonucleotides covering different parts of oriTpIP501 were subjected to binding with TraA and TraAN246. The KD of the protein–DNA complex encompassing the inverted repeat, the nick site and an additional 7 bases was found to be 55 nM for TraA and 26 nM for TraAN246. The unfolding of both protein constructs was monitored by measuring the change in the CD signal at 220 nm upon temperature change. The unfolding transition of both proteins occurred at approx. 42 °C. CD spectra measured at 20 °C showed 30% ?-helix and 13% ?-sheet for TraA, and 27% ?-helix and 18% ?-sheet content for the truncated protein. Upon DNA binding, an enhanced secondary structure content and increased thermal stability were observed for the TraAN246 protein, suggesting an induced-fit mechanism for the formation of the specific relaxase–oriT complex. PMID:15554903

Kopec, Jolanta; Bergmann, Alexander; Fritz, Gerhard; Grohmann, Elisabeth; Keller, Walter

2004-01-01

152

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

PubMed Central

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

2013-01-01

153

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

PubMed Central

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

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

2013-01-01

154

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

2014-10-01

155

Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.  

PubMed

The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9?±?4.9 years. The median duration on antiretroviral therapy was 16.2?±?12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases. PMID:24352130

Jordan, Mr; Obeng-Aduasare, Y; Sheehan, H; Hong, Sy; Terrin, N; Duong, Dv; Trung, Nv; Wanke, C; Kinh, Nv; Tang, Am

2013-12-18

156

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

PubMed Central

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

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

2014-01-01

157

Sexual risk taking and club drug use across three age cohorts of HIV-positive gay and bisexual men in New York City  

Microsoft Academic Search

This study examined club drug use (i.e., cocaine, ecstasy, ketamine, gamma-hydroxybutyrate [GHB], and methamphetamine) and unprotected anal intercourse (UAI) in an ethnically and racially diverse sample of 166 New York City-based seropositive, club drug-using, gay and bisexual men, ages 19–61, and considered these behaviors in relation to age category (20s, 30s, and 40 +) and number of years living with

Molly K. Pappas; Perry N. Halkitis

2011-01-01

158

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

159

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

Microsoft Academic Search

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

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

2007-01-01

160

Drug Addiction  

Microsoft Academic Search

\\u000a Many drugs of abuse, including cannabinoids, opioids, alcohol and nicotine, can alter the levels of endocannabinoids in the\\u000a brain. Recent studies show that release of endocannabinoids in the ventral tegmental area can modulate the reward-related\\u000a effects of dopamine and might therefore be an important neurobiological mechanism underlying drug addiction. There is strong\\u000a evidence that the endocannabinoid system is involved in

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

161

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

PubMed Central

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

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

2014-01-01

162

TBM shows superior sample size estimates over traditional clinical measures; fewer patients are needed for evaluating new drugs. A 24-month trial provides most power, except when patient attrition exceeds 15-16%/year, in which case a 12-month trial is opt  

E-print Network

TBM shows superior sample size estimates over traditional clinical measures; fewer patients cognitive measures in their precision and power to track disease progression, greatly reducing sample size estimates for drug trials. In the largest TBM study to date, we studied how sample size estimates

Thompson, Paul

163

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

164

CD30+ lymphomatoid drug reactions.  

PubMed

We report 5 cases of cutaneous CD30+ lymphomatoid drug reactions that occurred shortly after the onset of drug exposure and resolved promptly upon withdrawal of the offending agents. The cases showed protean dermatologic manifestations ranging from diffuse erythema with desquamation to macules, papules, and annular plaques. The suspect drugs were amlodipine (a calcium channel blocker) for 2 cases, sertraline (a selective serotonin reuptake inhibitor) for 1 case, gabapentin for 1 case, and levofloxacin (a fluoroquinolone) versus cefepime (a fourth generation cephalosporin), and metoprolol (a beta blocker), in the fifth case. The histopathologic findings included varying combinations of spongiotic dermatitis, lichenoid infiltrates, and interface dermatitis with a dermal infiltrate of large atypical lymphocytes. Three of the 5 cases contained as much as 30% CD30+ staining of all lymphocytes, whereas the remaining 2 showed 5%-15% positivity. Three patients had a history of allergy or immune dysregulation. Increased knowledge of CD30 positivity in lymphomatoid drug reactions may be relevant in an era of targeted drug therapies. Recognition of these findings may help clinicians to tailor appropriate clinical evaluation and treatment including a review of medications and the removal of possible offending agents. PMID:23328787

Pulitzer, Melissa P; Nolan, Katherine A; Oshman, Robin G; Phelps, Robert G

2013-05-01

165

Down-regulation of miR-199b associated with imatinib drug resistance in 9q34.1 deleted BCR/ABL positive CML patients.  

PubMed

Chronic myeloid leukemia (CML) occurs due to t(9,22) (q34;q11) and molecularly BCR/ABL gene fusion. About 15-18% Philadelphia positive CML patients have gene deletions around the translocation breakpoints on 9q34.1. The microRNAs (miRNAs), namely miR-219-2 and miR-199b, centromeric to the ABL1 gene are frequently lost in CML patients. We have designed a study to determine miR-219-2 and miR-199b expression levels which would help to understand the prognosis of imatinib therapy. A total of 150 CML patients were analyzed to identify 9q deletion. Fluorescent in-situ hybridization (FISH) was performed using BCR/ABL dual color, dual fusion probe to study the signal pattern and BAC probes for miR-199b and miR-219-2 (RP11-339B21 and RP11-395P17) to study the miRNA deletions. The expression level of miRNA was analyzed by real-time polymerase chain reaction (RT-PCR). FISH analysis revealed 9q34.1 deletion in 34 (23%) CML patients. The deletions were not detected using BAC probes for miRNAs in 9q deleted patients. The expression analysis showed down-regulation of miR-199b and miR-219-2 in the 9q deleted patients (34 CML) as compared to a pool of patients without deletion. However, miR-199b (9q34.11) was significantly (p=0.001) down-regulated compared to miR-219-2. The follow-up study showed that the miR-199b was found to be strongly associated with imatinib resistance, as 44.11% patients showed resistance to imatinib therapy. Hence, the deletion in 9q34.1 region (ABL) plays an important role in disease pathogenesis. Eventually, miRNAs can provide new therapeutic strategies and can be used as a prognostic indicator. PMID:24680705

Joshi, Dolly; Chandrakala, S; Korgaonkar, Seema; Ghosh, Kanjaksha; Vundinti, Babu Rao

2014-06-01

166

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

Microsoft Academic Search

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

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

2008-01-01

167

The Diane Rehm Show  

NSDL National Science Digital Library

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

168

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

PubMed

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

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

2014-02-01

169

Club Drugs  

MedlinePLUS

... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

170

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

171

Drug Tolerance, Drug Addiction, and Drug Anticipation  

Microsoft Academic Search

Environmental cues associated with drugs often elicit withdrawal symptoms and relapse to drug use. Such cues also modulate drug tolerance. The contribution of drug-associated stimuli to withdrawal and tolerance is emphasized in a Pavlovian-conditioning analysis of drug administration. Conditional responses occur in the presence of cues that have been associated with the drug in the past, such as the setting

Shepard Siegel

2005-01-01

172

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

173

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.

2009-04-06

174

Do Elephants Show Empathy?  

Microsoft Academic Search

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

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

2008-01-01

175

ISU Demonstration Road Show  

NSDL National Science Digital Library

The Idaho State University Department of Physics conducts science demonstration shows at SE Idaho schools. Four different presentations are currently available; "Forces and Motion", "States of Matter", "Electricity and Magnetism", and "Sound and Waves". Student activities and descriptions of the demonstrated material are also provided.

Shropshire, Steven

2004-04-06

176

Stage a Water Show  

ERIC Educational Resources Information Center

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

Frasier, Debra

2008-01-01

177

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

178

Show-Me Magazine  

NSDL National Science Digital Library

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

2008-01-01

179

Reconceptualising drug markets and drug dealers — the need for change  

Microsoft Academic Search

This paper outlines how, in many ways, the drug market is not what it is commonly assumed to be and that, as such, we need to reconceptualise how we understand both the drug market and the drug dealer. It briefly reviews the research showing that many of the core activities thought to characterise drug markets and drug dealing are unreasonably

Ross Coomber

2010-01-01

180

Mars Slide Show  

NASA Technical Reports Server (NTRS)

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

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

2006-01-01

181

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

PubMed

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

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

2011-01-01

182

Drugs of abuse, driving and traffic safety.  

PubMed

Roadside studies indicate that 1-15% of drivers drive under the influence of one or more drugs of abuse. After drug use, drivers are more often culpable for an accident than non-users. Information on drugs and traffic safety comes from roadside studies, epidemiological research, experimental studies on driving-related skills, and on-the-road driving tests. Road-side studies show that drivers most frequently test positive for the use of alcohol and/or cannabis. These two drugs affect driving ability in a dose-dependent matter and result in poor vehicle control, especially when used in combination. Drivers on cocaine, ecstasy and amphetamine show no impairment on basic driving skills, but often overestimate their driving skills. In combination with impaired decision making, this increases risk taking during driving. Only few studies looked at the effects on driving of other drugs of abuse, such as ketamine, inhalants and anabolic steroids, but suggest a negative effect on driving performance. In conclusion, most drugs of abuse negatively affect driving ability, especially when used in combination with alcohol or another drug. It is of concern that a substantial number of drug users are not aware that their driving is impaired. PMID:20088818

Penning, Renske; Veldstra, Janet L; Daamen, Anne P; Olivier, Berend; Verster, Joris C

2010-03-01

183

NPR: The Picture Show  

NSDL National Science Digital Library

National Public Radio's "The Picture Show" photo blog is a great way to avoid culling through the thousands of less interesting and engaging photographs on the web. With a dedicated team of professionals, this blog brings together different posts that profile various sets of photographs that cover 19th century war in Afghanistan, visual memories of WWII, unpublished photographs of JFK's presidential campaign, and abandoned buildings on the islands in Boston Harbor. Visitors can search through previous posts, use social media features to share the photo features with friends, and also sign up to receive new materials via their RSS feed. There's quite a nice mix of material here, and visitors can also comment on the photos and recommend the collection to friends and others.

184

Solar Light Show  

NSDL National Science Digital Library

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

de Nie, Michael Willem.

185

Egg: the Arts Show  

NSDL National Science Digital Library

"Egg is a new TV show about people making art across America" from PBS. This accompanying Website presents excerpts from sixteen episodes of the series, with three more "hatching soon," such as Close to Home, profiling three photographers: Jeanine Pohlhaus, whose pictures document her father's struggle with mental illness; Gregory Crewdson's photos of Lee, Massachusetts; and Joseph Rodriguez's photos of Hispanics in New York City. Excerpts include video clips, gallery listings where the artists' work can be seen, and short interviews with artists. Some episodes also offer "peeps," glimpses of material not shown on TV, such as the Space episode's peep, Shooting Stars, that provides directions for astrophotography, taking photographs of star trails. Other sections of the site are airdates, for local listings; see and do usa, where vacationers can search for art events at their destinations; and egg on the arts, a discussion forum.

186

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 ...

187

Public medical shows.  

PubMed

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

Walusinski, Olivier

2014-01-01

188

The Great Cometary Show  

NASA Astrophysics Data System (ADS)

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

2007-01-01

189

Synthesis and characterization of positively charged tPA as a prodrug using a heparin\\/protamine-based drug-delivery system  

Microsoft Academic Search

Positively charged peptides [(Arg)-Cys] were sucessfully linked to tissue-specific plasminogen activator (tPA) using cross-linking\\u000a agent N-succinimidyl 3-(2-pyridyldithio) propionate. Specific amidolytic activity of this tPA\\/(Arg)-Cys (termed modified tPA,\\u000a mtPA) was 3900 IU\\/?g as compared to 5800 IU\\/?g of the parent tPA. Both activation of plasminogen with mtPA (Km=2.7 mM?1) and tPA (Km=1.1 mM?1) in a purified system followed Michaelis-Menten kinetics. In

Jun F. Liang; Yong T. Li; Maureen E. Connell; Victor C. Yang

2000-01-01

190

Drug Reactions  

MedlinePLUS

... version Drug Reactions Drug Reactions What is an adverse drug reaction? Medicines can treat or prevent illness and ... medicines can cause problems. These problems are called adverse drug reactions. You should know what to do if ...

191

Drug Safety  

MedlinePLUS

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

192

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

Microsoft Academic Search

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

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

2003-01-01

193

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

ERIC Educational Resources Information Center

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

Elliott, Karen; Shelley, Kyna

2006-01-01

194

Redefining America's "War on Drugs"  

E-print Network

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

McQuade, D. Tyler

195

Microfluidic device for drug delivery  

NASA Technical Reports Server (NTRS)

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

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

2010-01-01

196

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

E-print Network

, industrial, consumer, and portable electronics". The IC group produces power ICs for motor drivers, motor), industrial, automotive and portable electronics markets. Electrical Engineering No Entry LevelCompany: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description

New Hampshire, University of

197

Generic Drugs  

MedlinePLUS

... about brand-name drugs. Resources Consumer Reports Best Buy Drugs can help you find lower-cost generic ... produced by Consumers Union and Consumer Reports Best Buy Drugs, a public information project supported by grants ...

198

Club Drugs  

MedlinePLUS

... include GHB, Rohypnol®, ketamine, and others. MDMA (Ecstasy) , Methamphetamine , and LSD (Acid) , are considered club drugs and ... drugs within this classification of drugs. En Español Methamphetamine (Research Reports) Published April 1998 . Revised September 2013 . ...

199

Preclinical validation of Aurora kinases-targeting drugs in osteosarcoma  

PubMed Central

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

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

2013-01-01

200

Drug interactions with alcohol.  

PubMed

Ethanol and drugs can affect each other's absorption, distribution, metabolism, and excretion. When ingested together, ethanol can increase drug absorption by enhancing the gastric solubility of drugs and by increasing gastrointestinal blood flow. However, high concentrations of ethanol induce gastric irritation causing a pyloric spasm which in turn may delay drug absorption and/or reduce bioavailability. The 'quality' of the alcoholic beverage, independent of its ethanol content, can contribute to altered absorption of a drug. Ethanol is not bound to plasma proteins extensively enough to modify drug distribution. However, serum albumin levels in chronic alcoholics may be abnormally low so that some drugs, e.g. diazepam, have an increased volume of distribution. In addition to the amount ingested, the duration of regular intake determines the effect of ethanol on drug metabolism. Acute intake of ethanol inhibits the metabolism of many drugs but long term intake of ethanol at a high level (greater than 200g of pure ethanol per day) can induce liver enzymes to metabolise drugs more efficiently. At the present time there are no accurate means, with the possible exception of liver biopsy, to clinically predict the capacity of an alcoholic to metabolise drugs. Several drugs can inhibit the metabolism of ethanol at the level of alcohol dehydrogenase. Individual predisposition determines the severity of this drug-ethanol interaction. During its absorption phase, ethanol inhibits the secretion of antidiuretic hormone and is also able to induce increased excretion of a drug through the kidneys. However, chronic alcoholics with water retention may show reduced excretion of drugs via this route. At the pharmacodynamic level, ethanol can enhance the deleterious effects of sedatives, certain anxiolytics, sedative antidepressants and antipsychotics and anticholinergic agents, on performance. Mechanisms of lethal interactions between moderate overdoses of ethanol and anxiolytics/opiates/sedatives are poorly understood. On the other hand, certain peptides, 'nonspecific' stimulants, dopaminergic agents and opiate antagonists can antagonise alcohol-induced inebriation to a significant degree. PMID:387374

Linnoila, M; Mattila, M J; Kitchell, B S

1979-10-01

201

Drug Facts  

MedlinePLUS Videos and Cool Tools

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

202

In silico modeling to predict drug-induced phospholipidosis  

SciTech Connect

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

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

2013-06-01

203

Patents Associated with High-Cost Drugs in Australia  

PubMed Central

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

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

2013-01-01

204

Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function  

PubMed Central

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

Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

2014-01-01

205

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

E-print Network

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

Grissino-Mayer, Henri D.

206

Soccer Tournament ELI Talent Show  

E-print Network

Highlights Soccer Tournament ELI Talent Show Notes from your Teachers Notes from the Office very quickly! ELI Talent Show As you probably already know, the ELI is going to have its second annual Talent Show. The talent show is open to ELI students, faculty, staff, and LAs. Acts can include

Pilyugin, Sergei S.

207

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

E-print Network

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

Gross, Louis J.

208

Drug Interactions  

MedlinePLUS

... opium Drugs to treat erectile dysfunction, such as Viagra Drugs used to treat tuberculosis, especially rifampin Other ... could result in an unwanted pregnancy. WHAT ABOUT HERBAL PRODUCTS? There has been very little research on ...

209

Club Drugs  

MedlinePLUS

Club drugs are group of psychoactive drugs. They act on the central nervous system and can cause changes ... K, and Jet Rohypnol, also known as Roofies Methamphetamine, also known as Speed, Ice, Chalk, Meth, Crystal, ...

210

Prescription Drugs  

MedlinePLUS

... at once. This effect increases the risk for addiction and overdose. Side effects. Prescription drugs are designed ... of these types of medications can lead to addiction. And, abusing any type of drug that causes ...

211

Show Them You Really Want the Job  

ERIC Educational Resources Information Center

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

Perlmutter, David D.

2012-01-01

212

Fellowships & Positions  

Cancer.gov

Fellowships & Positions The NCI Division of Cancer Prevention is part of the National Institutes of Health (NIH), U.S. Department of Health and Human Services. Current Openings Position Title Number of Openings Cancer Prevention Fellowship Program

213

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 — ...

214

Drug Cravings  

NSDL National Science Digital Library

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

Science Update;

2003-07-14

215

Drug kinetics and drug resistance in optimal chemotherapy  

Microsoft Academic Search

A system of differential equations for the control of tumor cells growth in a cycle nonspecific chemotherapy is presented. First-order drug kinetics and drug resistance are taken into account in a class of optimal control problems. The results show that the strategy corresponding to the maximum rate of drug injection is optimal for the Malthusian model of cell growth (which

J. L. Boldrini; R. C. Bassanezi

1995-01-01

216

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 ...

217

ELI Talent Show Final Exams  

E-print Network

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

Pilyugin, Sergei S.

218

Influences of motivational contexts on prescription drug misuse and related drug problems.  

PubMed

Prescription drug misuse has emerged as a significant problem among young adults. While the effects of motivational contexts have been demonstrated for illicit drugs, the role of motivational contexts in prescription drug misuse remains understudied. Using data from 400 young adults recruited via time-space sampling, we examined the role of motivational contexts in the frequency of misuse of three prescription drug types as well as drug-related problems and symptoms of dependency. Both negative and positive motivations to use drugs are associated with increases in prescription drug misuse frequency. Only negative motivations are associated directly with drug problems and drug dependence, as well as indirectly via prescription pain killer misuse. Addressing positive and negative motivational contexts of prescription drug misuse may not only provide a means to reduce misuse and implement harm reduction measures, but may also inform the content of treatment plans for young adults with prescription drug misuse problems. PMID:25115134

Kelly, Brian C; Rendina, H Jonathon; Vuolo, Mike; Wells, Brooke E; Parsons, Jeffrey T

2015-01-01

219

10 CFR 707.14 - Action pursuant to a determination of illegal drug use.  

Code of Federal Regulations, 2011 CFR

...DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES ...determination of use of illegal drugs by that employee (for example...tested positive for use of illegal drugs), the employee may...positive test result for illegal drugs. (2)...

2011-01-01

220

10 CFR 707.14 - Action pursuant to a determination of illegal drug use.  

Code of Federal Regulations, 2012 CFR

...DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES ...determination of use of illegal drugs by that employee (for example...tested positive for use of illegal drugs), the employee may...positive test result for illegal drugs. (2)...

2012-01-01

221

10 CFR 707.14 - Action pursuant to a determination of illegal drug use.  

Code of Federal Regulations, 2013 CFR

...DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES ...determination of use of illegal drugs by that employee (for example...tested positive for use of illegal drugs), the employee may...positive test result for illegal drugs. (2)...

2013-01-01

222

10 CFR 707.14 - Action pursuant to a determination of illegal drug use.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES ...determination of use of illegal drugs by that employee (for example...tested positive for use of illegal drugs), the employee may...positive test result for illegal drugs. (2)...

2010-01-01

223

10 CFR 707.14 - Action pursuant to a determination of illegal drug use.  

Code of Federal Regulations, 2014 CFR

...DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES ...determination of use of illegal drugs by that employee (for example...tested positive for use of illegal drugs), the employee may...positive test result for illegal drugs. (2)...

2014-01-01

224

Fixed drug eruption to tartrazine.  

PubMed

An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions. PMID:9431719

Orchard, D C; Varigos, G A

1997-11-01

225

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

PubMed Central

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

Kurzban, Robert; Dukes, Amber; Weeden, Jason

2010-01-01

226

Satellite positioning  

NASA Technical Reports Server (NTRS)

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

Colombo, Oscar L.; Watkins, Michael M.

1991-01-01

227

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

228

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

229

Contribution of Saccadic Motion to Intravitreal Drug Transport: Theoretical Analysis  

PubMed Central

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

Balachandran, Ram K.

2011-01-01

230

Drug Rash (Unclassified Drug Eruption) in Adults  

MedlinePLUS

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

231

Drug Research  

NASA Technical Reports Server (NTRS)

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

1989-01-01

232

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

233

Interoception and Drug Addiction  

PubMed Central

The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an “embodied” experience of drug uses together with the individual’s predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. PMID:23855999

Paulus, Martin P.; Stewart, Jennifer L.

2013-01-01

234

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

235

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. PMID:19421369

Jiang, Bingbing; Li, Bingyun

2009-01-01

236

Can antiarrhythmic drugs cause arrhythmia?  

PubMed

The recognition that certain types of ventricular premature beats, specifically repetitive forms, may be forerunners of more serious tachyarrhythmias has led to the practice of prophylactic therapy with antiarrhythmic drugs to suppress these forms in patients who have underlying cardiac disease. Several antiarrhythmic drugs are available for oral therapy, and many others are undergoing investigation. The usefulness of these agents is often limited by frequent side effects, which include idiosyncratic and unpredictable reactions that are not related to drug level. One such effect is the aggravation of the arrhythmia being treated. Noninvasive drug testing in 245 patients for a total of 1024 single drug tests showed 113 studies (11 per cent) to have been aggravated by the antiarrhythmic drug. At least one drug was proarrhythmic in 78 patients (32 per cent). Aggravation of arrhythmia is a potentially serious drug complication that occurs with all antiarrhythmic agents. PMID:6480877

Podrid, P J

1984-07-01

237

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

238

Map showing of UT's Main,  

E-print Network

$ $ Map showing locations of UT's Main, Scott Park, and Health Science Campuses Student Parking HEALTH SCIENCE CAMPUS GLENDALE BANCROFT NEBRASKA DETROIT FERI A NG BUILDING DIRECTORY AC Scott Park..........................................WBReceiving..........................................WB Minority Business Development Ctr....FAMinority Business Development Ctr....FA NorthwestNorthwest State

Viola, Ronald

239

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

240

Diarrheal Disease in Show Swine  

E-print Network

or short-term diarrhea followed by systemic or blood stream infection. E-439 3-07 *Visiting Professor, Swine Practice, College of Veterinary Medicine and Biomedical Sciences, The Texas A&M University System. Diarrheal Disease in Show Swine Bruce Lawhorn...

Lawhorn, D. Bruce

2007-02-27

241

Browse the archive Show summaries  

E-print Network

for consumers? www.fightthepowergrab.o Slide Shows for Physics MathType for science and math presentations that a "fast ignition" laser facility could make a significant contribution to fusion research, as well than magnets to confine the plasma, will be investigated by the National Ignition Facility (NIF

242

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.

243

Prescription Drug Abuse  

MedlinePLUS

... and drugs > Prescription drug abuse Overview FAQ Prescription drug abuse Sometimes you may need prescription drugs to treat ... medicine given by a health care provider . Prescription drug abuse is when you use a prescription drug in ...

244

Towards global network positioning  

Microsoft Academic Search

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

T. S. Eugene Ng; Hui Zhang

2001-01-01

245

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

246

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.

247

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

PubMed

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

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

2014-09-01

248

Random drug tests at work: the probability of identifying frequent and infrequent users of illicit drugs.  

PubMed

Random drug testing in the workplace has become more common since federal guidelines were issued in 1988, despite the criticism that most positive tests are the result of occasional use of illicit drugs. In order to determine the relative probabilities of detecting frequent versus infrequent users of illicit drugs, a survey of 15 experts in the drug abuse field was conducted. Based on the responses, it was estimated that 55% of employed people who used any illicit drugs in the prior year were annual drug users, 37% were monthly users, and 8% were daily users. Analysis using probability theory indicated that among workplace drug users who test positive, 52% will be daily users, 41% will be monthly users, and only 7% will be annual users. At a 50% testing rate, random drug tests identify 40% of daily users, 8% of monthly users and only 1% of annual users during the course of a year. The estimated rate of illicit drug use among employees is approximately eight times the average random testing positive rate. Random drug tests in the workplace are effective in identifying near daily users of illicit drugs, but they are less effective at identifying infrequent drug users. Employers have found that random drug testing is a deterrent to both frequent and occasional use of illicit drugs. PMID:8555274

DuPont, R L; Griffin, D W; Siskin, B R; Shiraki, S; Katze, E

1995-01-01

249

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

250

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

E-print Network

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

New Hampshire, University of

251

Golgi Positioning  

PubMed Central

The Golgi apparatus in mammalian cells is positioned near the centrosome-based microtubule-organizing center (Fig. 1). Secretory cargo moves inward in membrane carriers for delivery to Golgi membranes in which it is processed and packaged for transport outward to the plasma membrane. Cytoplasmic dynein motor proteins (herein termed dynein) primarily mediate inward cargo carrier movement and Golgi positioning. These motors move along microtubules toward microtubule minus-ends embedded in centrosomes. Centripetal motility is controlled by a host of regulators whose precise functions remain to be determined. Significantly, a specific Golgi receptor for dynein has not been identified. This has impaired progress toward elucidation of membrane-motor-microtubule attachment in the periphery and, after inward movement, recycling of the motor for another round. Pericentrosomal positioning of the Golgi apparatus is dynamic. It is regulated during critical cellular processes such as mitosis, differentiation, cell polarization, and cell migration. Positioning is also important as it aligns the Golgi along an axis of cell polarity. In certain cell types, this promotes secretion directed to the proximal plasma membrane domain thereby maintaining specializations critical for diverse processes including wound healing, immunological synapse formation, and axon determination. PMID:21504874

Yadav, Smita; Linstedt, Adam D.

2011-01-01

252

Drug-Drug Interactions: Antiretroviral Drugs and Recreational Drugs.  

PubMed

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

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

2014-11-26

253

Drug allergy  

PubMed Central

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

Warrington, Richard

2012-01-01

254

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

PubMed Central

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

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

2014-01-01

255

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

PubMed

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

Couto, Mariana; Silva, Diana; Ferreira, Ana; Cernadas, Josefina R

2014-09-01

256

Genome position and gene amplification  

Microsoft Academic Search

BACKGROUND: Amplifications, regions of focal high-level copy number change, lead to overexpression of oncogenes or drug resistance genes in tumors. Their presence is often associated with poor prognosis; however, the use of amplification as a mechanism for overexpression of a particular gene in tumors varies. To investigate the influence of genome position on propensity to amplify, we integrated a mutant

Pavla Gajduskova; Antoine M Snijders; Serena Kwek; Ritu Roydasgupta; Jane Fridlyand; Taku Tokuyasu; Daniel Pinkel; Donna G Albertson

2007-01-01

257

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

258

Drug delivery Combinatorial Drug Conjugation Enables Nanoparticle  

E-print Network

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

Zhang, Liangfang

259

Neural Effects of Positive and Negative Incentives during Marijuana Withdrawal  

PubMed Central

In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms. PMID:23690923

Filbey, Francesca M.; Dunlop, Joseph; Myers, Ursula S.

2013-01-01

260

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

Microsoft Academic Search

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

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

2007-01-01

261

Relationships between positive real, passive dissipative, & positive systems  

Microsoft Academic Search

This paper shows how: i) (strongly) positive real; ii) (asymptotically stable) dissipative (strictly-input) passive; and iii) (Lm2-stable strictly) positive; continuous time system definitions are equivalent for linear time invariant (LTI) systems. In parallel this paper shows how: i) (strictly) positive real; ii) (asymptotically stable) dissipative (strictly-input) passive; and iii) (lm2-stable strictly) positive; discrete time system definitions are equivalent for LTI

N. Kottenstette; Panos J. Antsaklis

2010-01-01

262

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

263

Why we should be vigilant: drug cytotoxicity observed with in vitro transporter inhibition studies.  

PubMed

From routine in vitro drug-transporter inhibition assays, observed inhibition is typically assumed from direct interaction with the transporter. Other mechanisms that possibly reduce substrate uptake are not frequently fully examined. The objective of this study was to investigate the association of transporter inhibition with drug cytotoxicity. From a pool of drugs that were identified as known ASBT or OCTN2 inhibitors, 21 drugs were selected to screen inhibitory potency of their prototypical substrate and cytotoxicity against three human sodium-dependent solute carrier (SLC) transporters: apical sodium-dependent bile acid transporter (ASBT), organic cation/carnitine transporter (OCTN2), and the excitatory amino acid transporter 4 (EAAT4) in stable cell lines. Twenty drugs showed apparent inhibition in OCTN2-MDCK and ASBT-MDCK. Four dihydropyridine calcium channel blockers were cytotoxic to MDCK cells, and the observed cytotoxicity of three of them accounted for their apparent OCTN2 inhibition, and consequently were classified as non-OCTN2 inhibitors. Meanwhile, since their cytotoxicity only moderately contributed to ASBT inhibition, these three were still considered ASBT inhibitors. Four other drugs showed apparent inhibition in EAAT4-HEK cells, and cytotoxicity of three drugs corresponded with their inhibition of this transporter. Therefore, cytotoxicity significantly affected EAAT4 observations. Results showed the potential of cytotoxicity as a mechanism that can account for apparent in vitro transporter inhibition. Drug cytotoxicity varied in different cell lines, which could increase false positives for pharmacophore development. PMID:20599790

Zheng, Xiaowan; Diao, Lei; Ekins, Sean; Polli, James E

2010-10-01

264

Racial Differences in Graduation Rates From Adult Drug Treatment Courts  

Microsoft Academic Search

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

Jerome McKean; Kiesha Warren-Gordon

2011-01-01

265

AIDSinfo Drug Database  

MedlinePLUS

... Widgets Order Publications Skip Nav AIDS info Drug Database Home > Drugs Español Text Size Drugs by class ... health care providers and patients. Search the Drug Database Help × Search by drug name Performs a search ...

266

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

PubMed Central

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

2010-01-01

267

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

268

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

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

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

269

A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery  

E-print Network

A New Brain Drug Delivery Strategy: Focused Ultrasound-Enhanced Intranasal Drug Delivery Hong Chen1 the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within

Konofagou, Elisa E.

270

Utility of Alkylaminoquinolinyl Methanols as New Antimalarial Drugs?  

PubMed Central

Mefloquine has been one of the more valuable antimalarial drugs but has never reached its full clinical potential due to concerns about its neurologic side effects, its greater expense than that of other antimalarials, and the emergence of resistance. The commercial development of mefloquine superseded that of another quinolinyl methanol, WR030090, which was used as an experimental antimalarial drug by the U.S. Army in the 1970s. We evaluated a series of related 2-phenyl-substituted alkylaminoquinolinyl methanols (AAQMs) for their potential as mefloquine replacement drugs based on a series of appropriate in vitro and in vivo efficacy and toxicology screens and the theoretical cost of goods. Generally, the AAQMs were less neurotoxic and exhibited greater antimalarial potency, and they are potentially cheaper than mefloquine, but they showed poorer metabolic stability and pharmacokinetics and the potential for phototoxicity. These differences in physiochemical and biological properties are attributable to the “opening” of the piperidine ring of the 4-position side chain. Modification of the most promising compound, WR069878, by substitution of an appropriate N functionality at the 4 position, optimization of quinoline ring substituents at the 6 and 7 positions, and deconjugation of quinoline and phenyl ring systems is anticipated to yield a valuable new antimalarial drug. PMID:16966402

Dow, G. S.; Heady, T. N.; Bhattacharjee, A. K.; Caridha, D.; Gerena, L.; Gettayacamin, M.; Lanteri, C. A.; Obaldia, N.; Roncal, N.; Shearer, T.; Smith, P. L.; Tungtaeng, A.; Wolf, L.; Cabezas, M.; Yourick, D.; Smith, K. S.

2006-01-01

271

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

272

Satellite positioning  

NASA Astrophysics Data System (ADS)

The Fifth International Geodetic Symposium on Satellite Positioning was held in Las Cruces, N.Mex., March 13-17, 1989. It was cosponsored by the Defense Mapping Agency and the National Geodetic Survey of the National Oceanic and Atmospheric Administration. More than 385 geodesists, engineers, scientists, surveyors, instrument manufacturers, and managers from 32 countries attended the symposium.The keynote address and 96 papers including 9 invited papers and 10 poster papers were presented in the 5-day meeting. In addition, there were three well-attended workshops with lively technical discussions. The invited guest presentations at the symposium luncheon and banquet provided very useful and interesting information.

Stein, William L.; Kumar, Muneendra

273

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

274

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

PubMed

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

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

2009-01-01

275

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

E-print Network

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

Gross, Louis J.

276

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

277

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

NASA Astrophysics Data System (ADS)

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

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

2014-07-01

278

Deficient supplies of drugs for life threatening diseases in an African community  

PubMed Central

Background In Malawi essential drugs are provided free of charge to patients at all public health facilities in order to ensure equitable access to health care. The country thereby spends about 30% of the national health budget on drugs. In order to investigate the level of drug shortages and eventually find the reasons for the drugs shortages in Malawi, we studied the management of the drug supplies for common and life threatening diseases such as pneumonia and malaria in a random selection of health centres. Methods In July and August 2005 we visited eight out of a total of 37 health centres chosen at random in the Lilongwe District, Malawi. We recorded the logistics of eight essential and widely used drugs which according to the treatment guidelines should be available at all health centres. Five drugs are used regularly to treat pneumonia and three others to treat acute malaria. Out-of-stock situations in the course of one year were recorded retrospectively. We compared the quantity of each drug recorded on the Stock Cards with the actual stock of the drug on the shelves at the time of audit. We reviewed 8,968 Patient Records containing information on type and amount of drugs prescribed during one month. Results On average, drugs for treating pneumonia were out of stock for six months during one year of observation (median value 167 days); anti-malarial drugs were lacking for periods ranging from 42 to138 days. The cross-sectional audit was even more negative, but here too the situation was more positive for anti-malarial drugs. The main reason for the shortage of drugs was insufficient deliveries from the Regional Medical Store. Benzyl penicillin was in shortest supply (4% received). The median value for non-availability was 240 days in the course of a year. The supply was better for anti-malarial drugs, except for quinine injections (9 %). Only 66 % of Stock Card records of quantities received were reflected in Patient Records showing quantities dispensed. Conclusion We conclude that for the eight index drugs the levels of supply are unacceptable. The main reason for the observed shortage of drugs at the health centres was insufficient deliveries from the Regional Medical Store. A difference between the information recorded on the Stock Cards at the health centres and that recorded in the Patient Records may have contributed to the overall poor drug supply situation. In order to ensure equitable access to life saving drugs, logistics in general should be put in order before specific disease management programmes are initiated. PMID:17573958

Lufesi, Norman N; Andrew, Marit; Aursnes, Ivar

2007-01-01

279

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

280

Benign positional vertigo  

MedlinePLUS

Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal positional ... ear has fluid-filled tubes called semicircular canals. When ...

281

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.

282

Drug therapy  

Microsoft Academic Search

Because of the lack of understanding of the basis of fibromyalgia, therapy remains empiric. This article reviews the different drug elements used in fibromyalgia, including psychotropic agents (antidepressants, sedatives and hypnotics), anti-inflammatories, analgesics and other pharmacological compounds. The strength of evidence for the therapeutic effect of each medicinal modality is presented, with the emphasis on results of randomized controlled trials.The

Dan Buskila

1999-01-01

283

Drug Resistance  

MedlinePLUS

... day and exactly as prescribed. What is drug resistance? Once a person becomes infected with HIV, the virus begins to multiply (make copies of itself) in the body. As HIV multiplies, it sometimes mutates (changes form) and produces variations of itself. Variations of ...

284

Drug delivery and nanoparticles: Applications and hazards  

PubMed Central

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. PMID:18686775

De Jong, Wim H; Borm, Paul JA

2008-01-01

285

Positioning of Nuclei in Arabidopsis Root Hairs  

PubMed Central

In growing Arabidopsis root hairs, the nucleus locates at a fixed distance from the apex, migrates to a random position during growth arrest, and moves from branch to branch in a mutant with branched hairs. Consistently, an artificial increase of the distance between the nucleus and the apex, achieved by entrapment of the nucleus in a laser beam, stops cell growth. Drug studies show that microtubules are not involved in the positioning of the nucleus but that subapical fine F-actin between the nucleus and the hair apex is required to maintain the nuclear position with respect to the growing apex. Injection of an antibody against plant villin, an actin filament-bundling protein, leads to actin filament unbundling and movement of the nucleus closer to the apex. Thus, the bundled actin at the tip side of the nucleus prevents the nucleus from approaching the apex. In addition, we show that the basipetal movement of the nucleus at root hair growth arrest requires protein synthesis and a functional actin cytoskeleton in the root hair tube. PMID:12417712

Ketelaar, Tijs; Faivre-Moskalenko, Cendrine; Esseling, John J.; de Ruijter, Norbert C. A.; Grierson, Claire S.; Dogterom, Marileen; Emons, Anne Mie C.

2002-01-01

286

Drug addiction: the neurobiology of disrupted self-control.  

PubMed

The nature of addiction is often debated along moral versus biological lines. However, recent advances in neuroscience offer insights that might help bridge the gap between these opposing views. Current evidence shows that most drugs of abuse exert their initial reinforcing effects by inducing dopamine surges in limbic regions, affecting other neurotransmitter systems and leading to characteristic plastic adaptations. Importantly, there seem to be intimate relationships between the circuits disrupted by abused drugs and those that underlie self-control. Significant changes can be detected in circuits implicated in reward, motivation and/or drive, salience attribution, inhibitory control and memory consolidation. Therefore, addiction treatments should attempt to reduce the rewarding properties of drugs while enhancing those of alternative reinforcers, inhibit conditioned memories and strengthen cognitive control. We posit that the time has come to recognize that the process of addiction erodes the same neural scaffolds that enable self-control and appropriate decision making. PMID:17070107

Baler, Ruben D; Volkow, Nora D

2006-12-01

287

Cigars Loaded with Harmful Toxins, Study Shows  

MedlinePLUS

... agents as cigarette smoking," lead author Dr. Jiping Chen, an epidemiologist at the U.S. Food and Drug ... carcinogen, are comparable in cigar and cigarette smokers," Chen said. Another expert in respiratory health agreed that ...

288

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

289

Drug models of schizophrenia  

PubMed Central

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

Steeds, Hannah; Carhart-Harris, Robin L.

2015-01-01

290

Drug models of schizophrenia.  

PubMed

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

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

2015-02-01

291

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 b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

Campbell, T J; Williams, K M

2001-01-01

292

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. PMID:9803978

Campbell, T J; Williams, K M

1998-01-01

293

DRUG NAME (INSERT DRUG NAME)  

Cancer.gov

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

294

Potential P-Glycoprotein-Mediated Drug-Drug Interactions of Antimalarial Agents in Caco-2 cells  

PubMed Central

Antimalarials are widely used in African and Southeast Asian countries, where they are combined with other drugs for the treatment of concurrent ailments. The potential for P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) between antimalarials and P-gp substrates was examined using a Caco-2 cell-based model. Selected antimalarials were initially screened for their interaction with P-gp based on the inhibition of rhodamine-123 (Rho-123) transport in Caco-2 cells. Verapamil (100 ?M) and quinidine (1 ?M) were used as positive inhibition controls. Lumefantrine, amodiaquin, and artesunate all showed blockade of Rho-123 transport. Subsequently, the inhibitory effect of these antimalarials on the bi-directional passage of digoxin (DIG) was examined. All of the drugs decreased basal-to-apical (B-A) P-gp-mediated DIG transport at concentrations of 100 ?M and 1 mM. These concentrations may reflect therapeutic doses for amodiaquin and artesunate. Therefore, clinically relevant DDIs may occur between certain antimalarials and P-gp substrates in general. PMID:22764293

Oga, Enoche F.; Sekine, Shuichi; Shitara, Yoshihisa; Horie, Toshiharu

2012-01-01

295

Drugs of abuse detection in saliva based on actuated optical method  

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

296

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

ERIC Educational Resources Information Center

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

James, William H.; Moore, David D.

1997-01-01

297

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. PMID:21103142

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

2010-01-01

298

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia  

PubMed Central

Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is under-recognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fiban-dependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20 × 109/L); bleeding complications; onset 5 to 10 days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and ideally should be reproducible across laboratories. Improved standardization and accessibility of laboratory testing should be a focus of future research. PMID:23845922

Arnold, Donald M.; Nazi, Ishac; Warkentin, Theodore E.; Smith, James W.; Toltl, Lisa J.; George, James N.; Kelton, John G.

2013-01-01

299

Transpapillary Drug Delivery to the Breast  

PubMed Central

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

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

2014-01-01

300

Drugs and Alcohol: Their Relative Crash Risk  

PubMed Central

Objective: The purpose of this study was to determine (a) whether among sober (blood alcohol concentration [BAC] = .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; (b) whether among drinking (BAC > .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; and (c) whether alcohol and other drugs interact in increasing crash risk. Method: We compared BACs for the 2006, 2007, and 2008 crash cases drawn from the U.S. Fatality Analysis Reporting System (FARS) with control drug and blood alcohol data from participants in the 2007 U.S. National Roadside Survey. Only FARS drivers from states with drug information on 80% or more of the drivers who also participated in the 2007 National Roadside Survey were selected. Results: For both sober and drinking drivers, being positive for a drug was found to increase the risk of being fatally injured. When the drug-positive variable was separated into marijuana and other drugs, only the latter was found to contribute significantly to crash risk. In all cases, the contribution of drugs other than alcohol to crash risk was significantly lower than that produced by alcohol. Conclusions: Although overall, drugs contribute to crash risk regardless of the presence of alcohol, such a contribution is much lower than that by alcohol. The lower contribution of drugs other than alcohol to crash risk relative to that of alcohol suggests caution in focusing too much on drugged driving, potentially diverting scarce resources from curbing drunk driving. PMID:24411797

Romano, Eduardo; Torres-Saavedra, Pedro; Voas, Robert B.; Lacey, John H.

2014-01-01

301

Street Drugs and Pregnancy  

MedlinePLUS

... been added to your dashboard . Street drugs and pregnancy A street drug (also called illegal or illicit ... are abused How can street drugs harm your pregnancy? Using street drugs can cause problems for you ...

302

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.

303

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

304

Drug abuse first aid  

MedlinePLUS

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

305

Familiar drugs may prevent cancer  

Microsoft Academic Search

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

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

2001-01-01

306

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

307

Understanding and Counseling the Chronic Drug User  

ERIC Educational Resources Information Center

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

Dyer, Wayne W.; Vriend, John

1975-01-01

308

[Drug Exposed Infants and Their Families.  

ERIC Educational Resources Information Center

This bulletin issue addresses the theme of drug-exposed infants and the services required by these infants and their families. "Cocaine-Exposed Infants: Myths and Misunderstandings" (Barbara J. Myers and others) comments on the negative accounts of drug-exposed babies presented by mass media and reviews the mix of positive and negative findings…

Fenichel, Emily, Ed.

1992-01-01

309

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.

310

Interaction network among functional drug groups  

PubMed Central

Background More attention has been being paid to combinatorial effects of drugs to treat complex diseases or to avoid adverse combinations of drug cocktail. Although drug interaction information has been increasingly accumulated, a novel approach like network-based method is needed to analyse that information systematically and intuitively Results Beyond focussing on drug-drug interactions, we examined interactions between functional drug groups. In this work, functional drug groups were defined based on the Anatomical Therapeutic Chemical (ATC) Classification System. We defined criteria whether two functional drug groups are related. Then we constructed the interaction network of drug groups. The resulting network provides intuitive interpretations. We further constructed another network based on interaction sharing ratio of the first network. Subsequent analysis of the networks showed that some features of drugs can be well described by this kind of interaction even for the case of structurally dissimilar drugs. Conclusion Our networks in this work provide intuitive insights into interactions among drug groups rather than those among single drugs. In addition, information on these interactions can be used as a useful source to describe mechanisms and features of drugs. PMID:24555875

2013-01-01

311

Impact of Psychotropic Drugs on QT Interval Dispersion in Adult Patients  

PubMed Central

Background Drug-induced increase in QT dispersion has been associated with potentially fatal ventricular arrhythmias. Little is known about the use of psychotropic substances, alone or in combination with other drugs on QT dispersion. Objectives To evaluate the impact of psychotropic drugs on QT interval dispersion in adults. Methods An observational cohort study was designed involving 161 patients hospitalized from an emergency department at a tertiary hospital, divided into psychotropic users or non-users. Demographic, clinical, laboratory data and drugs used on a regular basis were collected on admission, in addition to 12-lead electrocardiogram with QT dispersion measurement. Results QT dispersion was significantly higher in the psychotropic user group compared to non-users (69.25 ± 25.5 ms vs. 57.08 ± 23.4 ms; p = 0.002). The QT interval corrected by Bazzett formula was also higher in the psychotropic drugs user group, with statistical significance. (439.79 ± 31.14 ms vs. 427.71 ± 28.42 ms; p = 0.011). A regression analysis model showed a positive association between the number of psychotropic drugs used and QT interval dispersion, with r = 0.341 and p < 0.001. Conclusions The use of psychotropic drugs was associated with increased QT dispersion and this increase was accentuated, as the number of psychotropic drugs used was higher. PMID:24830389

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

2014-01-01

312

Anti-tumor necrosis factor drug survival in axial spondyloarthritis is independent of the classification criteria.  

PubMed

To compare the impact of meeting specific classification criteria [modified New York (mNY), European Spondyloarthropathy Study Group (ESSG), and Assessment of SpondyloArthritis international Society (ASAS) criteria] on anti-tumor necrosis factor (anti-TNF) drug retention, and to determine predictive factors of better drug survival. All patients fulfilling the ESSG criteria for axial spondyloarthritis (SpA) with available data on the axial ASAS and mNY criteria, and who had received at least one anti-TNF treatment were retrospectively retrieved in a single academic institution in Switzerland. Drug retention was computed using survival analysis (Kaplan-Meier), adjusted for potential confounders. Of the 137 patients classified as having axial SpA using the ESSG criteria, 112 also met the ASAS axial SpA criteria, and 77 fulfilled the mNY criteria. Drug retention rates at 12 and 24 months for the first biologic therapy were not significantly different between the diagnostic groups. Only the small ASAS non-classified axial SpA group (25 patients) showed a nonsignificant trend toward shorter drug survival. Elevated CRP level, but not the presence of bone marrow edema on magnetic resonance imaging (MRI) scans, was associated with significantly better drug retention (OR 7.9, ICR 4-14). In this cohort, anti-TNF drug survival was independent of the classification criteria. Elevated CRP level, but not positive MRI, was associated with better drug retention. PMID:25070142

Zufferey, Pascal; Ghosn, Jacqueline; Becce, Fabio; Ciurea, Adrian; Aubry-Rozier, Bérengère; Finckh, Axel; So, Alexander K

2014-07-29

313

Patterns of Drug Use in Fatal Crashes  

PubMed Central

Aims To characterize drug prevalence among fatally injured drivers, identify significant associations (i.e., day of week, time of day, age, gender), and compare findings with those for alcohol. Design Descriptive and logistic mixed-model regression analyses of Fatality Analysis Reporting System data. Setting U.S. states with drug test results for >80% of fatally injured drivers, 1998-2010. Participants Drivers killed in single-vehicle crashes on public roads who died at the scene of the crash (N=16,942). Measurements Drug test results, blood alcohol concentration (BAC), gender, age, and day and time of crash. Findings Overall, 45.1% of fatally injured drivers tested positive for alcohol (39.9% BAC>0.08) and 25.9% for drugs. The most common drugs present were stimulants (7.2%) and cannabinols (7.1%), followed by “other” drugs (4.1%), multiple drugs (4.1%), narcotics (2.1%), and depressants (1.5%). Drug-involved crashes occurred with relative uniformity throughout the day while alcohol-involved crashes were more common at night (p<.01). The odds of testing positive for drugs varied depending upon drug class, driver characteristics, time of day, and the presence of alcohol. Conclusions Fatal single vehicle crashes involving drugs are less common than those involving alcohol and the characteristics of drug-involved crashes differ depending upon drug class and whether alcohol is present. Concerns about drug-impaired driving should not detract from the current law enforcement focus on alcohol-impaired driving. PMID:23600629

Romano, Eduardo; Pollini, Robin A.

2013-01-01

314

Risk Behaviors Among HIV-Positive Gay and Bisexual Men at Party-Oriented Vacations  

PubMed Central

Objective: This study examined substance use (intended and actual), unprotected sex, and HIV disclosure practices (disclosure and questioning) among HIV-positive men who have sex with men (MSM) at two party-oriented vacations, where substance use and sexual risk may be heightened. Method: A random sample of 489 MSM attending one of two party-oriented vacations participated in PartyIntents, a short-term longitudinal survey. Nearly half (47%) completed a follow-up assessment at the event or online for up to 2 weeks after the event. We examined rates of baseline intentions to use substances, actual substance use, and unprotected intercourse among HIV-positive men in attendance.Rates among HIV-negative men were estimated for comparison. Multiple logistic regression was used to assess the impact of illegal drug use and HIV status on unprotected anal intercourse (UAI). Results: HIV-positive attendees (17%) were significantly more likely than HIV-negative attendees to use nitrite inhalants (or “poppers”) (24.3% vs. 10.7%). HIV-positive attendees were also significantly more likely to have insertive UAI (64.3% vs. 34.1%) and receptive UAI (68.8% vs. 22.2%). Multivariate models showed associations between HIV status and illegal drug use with UAI (for HIV status, odds ratio [OR] = 4.5, p = .001; for any illegal drug use, OR = 16.4, p < .001). There was no evidence that the influence of drug use moderated risk by HIV status. Rates of HIV disclosure and questioning did not differ by HIV status. Conclusions: HIV-positive men attending these events engaged in higher rates of illegal drug use and sexual risk than HIV-negative men. Prevention campaigns targeting MSM at high-risk events should include messages geared toward HIV-positive men. PMID:23200162

Fisher, Michael P.; Ramchand, Rajeev; Bana, Sarah; Iguchi, Martin Y.

2013-01-01

315

Atomic Level Rendering of DNA-Drug Encounter  

PubMed Central

Computer simulations have been demonstrated to be important for unraveling atomic mechanisms in biological systems. In this study, we show how combining unbiased molecular dynamic simulations with appropriate analysis tools can successfully describe metal-based drug interactions with DNA. To elucidate the noncovalent affinity of cisplatin’s family to DNA, we performed extensive all-atom molecular dynamics simulations (3.7 ?s total simulation length). The results show that the parent drug, cisplatin, has less affinity to form noncovalent adducts in the major groove than its aquo complexes. Furthermore, the relative position in which the drugs enter the major groove is dependent on the compound’s net charge. Based on the simulations, we estimated noncovalent binding free energies through the use of Markov state models. In addition, and to overcome the lack of experimental information, we employed two additional methods: Molecular Mechanics Poisson-Boltzmann Surface Area (MMPB-SA) and steered molecular dynamics with the Jarzynski estimator, with an overall good agreement between the three methods. All complexes show interaction energies below 3 kcal/mol with DNA but the charged hydrolysis products have slightly more favorable binding free energies than the parent drug. Moreover, this study sets the precedent for future unbiased DNA-ligand simulations of more complex binders. PMID:24461017

Lucas, Maria F.; Cabeza de Vaca, Israel; Takahashi, Ryoji; Rubio-Martínez, Jaime; Guallar, Víctor

2014-01-01

316

Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury)  

E-print Network

Drug Formulation / Drug Delivery Raj Suryanarayanan (Sury) Department of Pharmaceutics College)Physical Pharmaceutics (Materials Science) Suryanarayanan, Sun Drug Delivery K di ll P bh P Si l Wi dKandimalla, Prabha, Panyam, Siegel, Wiedmann 2 #12;#12;Center for Translational Drug Delivery Developing

Blanchette, Robert A.

317

Evolutionary inspirations for drug discovery.  

PubMed

Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs. PMID:20724009

Zhang, Hong-Yu; Chen, Ling-Ling; Li, Xue-Juan; Zhang, Jian

2010-10-01

318

Hepatitis C virus infection among drug addicts in Italy.  

PubMed

There is a lack of updated nationwide records regarding hepatitis C virus (HCV) infection among drug addicts in Italy. The prevalence and characteristics of HCV infection in a national sample of drug addicts in Italy were determined. Five hundred forty-three drug addicts (mean age 35.3 years, 85.1% males), selected from 25 Italian Centers for Substance Dependence were enrolled to be evaluated for anti-HCV, HCV-RNA, HCV genotype, HBV markers, anti-HDV, and anti-HIV during the period of April-November 2009. Anti-HCV prevalence was 63.9%. HCV-RNA was detected in 68.3% of patients positive for anti-HCV. Genotypes 1 and 3 prevailed (49.3% and 39.7%, respectively). However, 9.3% of the subjects had genotype 4, a rate over threefold higher than the one observed in 1996 among drug addicts in central Italy. Needle sharing was the strongest independent predictor of the likelihood to contract an HCV infection (OR 8.9; 95% CI: 5.0-16.0). Only 19.3% of subjects received antiviral treatment for HCV. The prevalence of HBsAg and HIV positivity was 2.8% and 3.1%, respectively. The pattern of HBV markers showed that nearly one-third of subjects had been vaccinated, while 42.3% were negative for any marker of HCV. The prevalence of HCV infection is high among drug addicts in Italy. The incidence of Genotype 4 is increasing and this may lead to the spreading of the disease to the general population in the near future. Efforts should be made to improve the rate of antiviral treatment for drug addicts with HCV infection and vaccination against hepatitis B. PMID:22930509

Stroffolini, T; D'Egidio, P F; Aceti, A; Filippini, P; Puoti, M; Leonardi, C; Almasio, P L

2012-10-01

319

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.

320

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

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

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

321

[Drug induced eosinophilic pleural effusion].  

PubMed

The hypersensitivity reactions induced by drugs, some widely used, like central nervous system medication, can have various presentations. The lung is a frequent target for such events. We present the case of 40-year-old male patient, non-smoker, with infant encephalopaty, seizures since age of 6 with polimorphic crisis (mainly absences), with anticonvulsivant treatment since 2011 (carbamazepine, sodium valproate, levetiracetam), with no respiratory medical history. Current symptoms started two weeks before, with chest pain, dry cough. He received no antibiotics. Chest X-ray and thoracic CT scan (27 June 2013) showed a left pleral effusion. Left exploratory thoracocentesis extracted 20 ml reddish pleural fluid: eosinophilic exsudate (60%) with normal adenosin deaminase. He also presents moderate blood eosinophilia (13.7%-1780/mm3). Pulmonary infarction with secondary pleurisy, thoracic trauma, acute pancreatitis with secondary pleurisy were excluded. No Loeffler transient infiltrates were documented, serology for Toxocara is IgG positive (historical) and not significant for current episode, no symptoms suggestive for toxocarosis (characteristic to young children, patient had no liver enlargement etc.), no hidatidosis or trichinelosis were found. As an exclusion diagnosis, a hypersensitivity reaction to anticonvulsivant medication was considered (mentioned in literature) carbamazepine and sodium valproate (even if medication was taken for a longer time), with blood and pleural eosinophilia. Together with the neurologist, the mentioned drugs were stopped and he was started on lamotrigine 2 tb/day and levetiracetam 1 tb/day, well tolerated, no absences were noticed. Total remission of blood eosinophilia and partial remission of pleural effusion were noticed. Subsequent follow-ups confirm favourable evolution, with healing of pleurisy and normal blood cell count, which are stable at 7 months after changing anticonvulsivant treatment. PMID:25241560

Vasilescu, Raluca

2014-01-01

322

Construction of Drug Network Based on Side Effects and Its Application for Drug Repositioning  

PubMed Central

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

Ye, Hao; Liu, Qi; Wei, Jia

2014-01-01

323

Drug-Induced Parkinsonism  

PubMed Central

Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders. PMID:22523509

Shin, Hae-Won

2012-01-01

324

[Resistance to antituberculous drugs].  

PubMed

Mycobacteria responsible for tuberculosis (M. tuberculosis, M. bovis, M. africanum) are susceptible to a very small number of antibiotics. As soon as these drugs were used in humans all gave rise to the selection of resistant mycobacteria. Study of the mechanisms of acquired resistance, with the help of the genetics of mycobacteria, led to a more accurate understanding of the mode of action of antituberculous drugs. The antibiotics isoniazid, pyrazinamide, ethionamide and ethambutol are mycobacteria-specific because they inhibit the synthesis of mycolic acids, which are specific constituants of the bacterial wall. Mutations responsible for resistance to these drugs affect genes coding for activator enzymes (katg for isoniazid, pncA for pyrazinamide) or genes coding for their target (inhA for isoniazid/ethionamide, embB for ethambutol). With rifamycins, aminosides and quinolones, mechanisms of action and resistance are the same for mycobacteria as for non-mycobacterial organisms. No plasmid or resistance transposon has been described in M. tuberculosis. Currently a test for the quick detection of resistance to rifampicin is widely available but in the future DNA chips may allow the simultaneous detection of multiple resistances. Monitoring of antituberculous drugs shows that in France the prevalence of multiresistance ( resistance to both isoniazid and rifampicin) is 0.5%, primary resistance (before treatment) is 9%, and secondary resistance (after treatment) is 16%. PMID:16129320

Veziris, N; Cambau, E; Sougakoff, W; Robert, J; Jarlier, V

2005-08-01

325

[Comparative study of drug efficacy and drug additives between generic drugs and original drugs].  

PubMed

In the present study, we tested three kinds of sleeping drugs, consisting mainly of triazolam, brotizolam, and flunitrazepam, to compare the drug efficacy of generic drugs with that of original drugs. After these drugs were administered orally to mice, drug efficacy was evaluated in terms of ambulation, onset time of sleep, and duration of sleep in the open field test. For all kinds of sleep-inducing drugs, the drug efficacy of most generic drugs is not necessarily equal to that of the original drug. The main reason for the difference appears to be due to differences in the rate of absorption of the main drug. Any other differences between an original drug and a generic drug are caused by drug additives, the crystal form of the main drug, the formulation, and so on. In this study, the formulation was not the reason for the differences because all of the drugs were pulverized in a mortar and had no special coating. The drug additives for all the drugs are listed and the drug efficacy compared. Unfortunately, the information was not sufficient to shed any light on the differences in drug efficacy. For effective drug therapy, more information on drug additives should be provided. PMID:18057791

Katoh, Hiromi; Yoshii, Michiko; Ozawa, Koichiro

2007-12-01

326

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

327

CCMR: Drug Delivery Using Nanoparticles  

NSDL National Science Digital Library

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

Lin, Joyce

2005-08-17

328

Methadone and its role in drug-related fatalities in Cologne 1989-2000.  

PubMed

All drug-associated deaths from 1989 to 2000 were analysed at the Institute of Forensic Medicine in Cologne. Information concerning sex, gender, drug consumption, time, place and circumstances of death were analysed. A number of 605 cases were recorded; in 518 cases a toxicological analysis was possible and in 171 an autopsy was performed. When it was possible to determine the cause of death form the information available, acute drug intoxication was recorded in 65%. Heroin head the list of identified substances. Sixty-three percent of the specimens showed a combination of several substances, especially a combination of morphine, benzodiazepines, other medications and alcohol. In comparison with other studies the percentage of methadone-positive specimens is low, even though the proportion of specimens positive for methadone increased from 1989 to 2000. This analysis is discussed using background information concerning the management of substitution therapy and the available literature. PMID:12711204

Grass, H; Behnsen, S; Kimont, H-G; Staak, M; Käferstein, H

2003-04-01

329

Studies Of Positive-Position-Feedback Control  

NASA Technical Reports Server (NTRS)

Report discusses theoretical and experimental studies of positive-position-feedback control for suppressing vibrations in large flexible structures. Positive-position-feedback control involves placement of actuators and sensors on structure; control voltages applied to actuators in response to outputs of sensors processed via compensator algorithm. Experiments demonstrate feasibility of suppressing vibrations by positive position feedback, and spillover of vibrational energy into uncontrolled modes has stabilizing effect if control gain sufficiently small.

Fanson, James L.; Caughey, Thomas K.

1992-01-01

330

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

331

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

332

Dynamics of Shoreline Position  

NASA Astrophysics Data System (ADS)

Change in the position of a shoreline over time results from the interaction of a large number of processes, which appear to produce a random pattern of change. Complexity analysis has been applied to a twenty-year record of mean high water shoreline positions surveyed approximately biweekly along four transects at Duck, NC. A Lomb Periodogram permits spectral analysis of the unevenly spaced data. The spectral analysis reveals that the signal is a 1/f noise with b, the scaling exponent, equal to one. Properties of 1/f noises are power-scaling, long-range persistence, and slight non-stationarity. Power-scaling signals exhibit spectral density that increase with wavelength, and contain no characteristic wavelength. Long-range persistence of a signal measures the temporal correlation among values of like magnitude relative to the mean. Non-stationarity of a signal measures the drift of the mean over time. Runs (successive movement in the same direction) for both erosion and accretion range from 1 to 7 consecutive surveys lasting from weeks to months and conform to a Gaussian distribution. The magnitudes of lateral excursions of shoreline position conforms to a Gaussian distribution with a mean of zero and a standard deviation of 3 meters. The size distribution of both runs and lateral excursions show a balance between erosion and accretion. The distributions derived from the field data were used to create a synthetic signal that is statistically identical to the shoreline position time series. In contrast to the field time series, the synthetic signal is uniformly spaced (daily) and is run for 100 years. The synthetic signal exhibits erosional and accretionary runs and excursions at all scales and drifts within a narrow envelope of plus or minus 30 meters. The size distributions of both runs and excursions in shoreline position indicate that they result from a Poissonian process, i.e. random, with no memory, analogous to a fair coin toss. But, the persistence measure, b=1, indicates that the position of the runs and excursions is not random in time. Thus, similar shoreline positions tend to cluster in time, so that a particular shoreline position is more likely to be followed by a similar position, rather than randomly distributed in time. The analysis indicates that the physical processes operating at this beach are self-organizing over a broad range of time scales, resulting in a stable shoreline position in the face of a high rate of sea level rise (calculated to be 5 cm/decade at this site).

Barton, C. C.; Dismukes, J. S.; Morton, R. A.

2002-12-01

333

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

334

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

ERIC Educational Resources Information Center

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

Page, Richard C.

1983-01-01

335

16 genes by positional approaches was reported (20). Retrospective analysis shows that 44% (7  

E-print Network

of structural and func- tional genomics, to comparative biology, and to the isolation of human disease genes, 339 (1996). The GB4 RH panel consists of 93 hamster cell lines, each retaining about 32% of the human RH panel consists of 83 hamster lines with a 16% retention freq

Terrace, Herbert S.

336

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

ERIC Educational Resources Information Center

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

DeRicco, Lawrence A.

337

Study Shows Elevated Number of Cancers in US HIV Positive Population  

Cancer.gov

In 2010, an estimated 7,760 new cancers were diagnosed among the nearly 900,000 Americans known to be living with HIV infection. According to the first comprehensive study in the United States, approximately half of these cancers were in excess of what would be expected if HIV-infected people had the same cancer risk as the general population.

338

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

PubMed Central

Background In this article, the test implementation of a school-oriented drug prevention program “Study without Drugs” is discussed. The aims of this study were to determine the results of the process evaluation and to determine whether the proposed school-oriented drug prevention program during a pilot project was effective for the participating pupils. Methods Sixty second-grade pupils at a junior high school in Paramaribo, Suriname participated in the test implementation. They were divided into two classes. For the process evaluation the students completed a structured questionnaire focusing on content and teaching method after every lesson. Lessons were qualified with a score from 0–10. The process was also evaluated by the teachers through structured interviews. Attention was paid to reach, dose delivered, dose received, fidelity, connection, achieved effects/observed behaviors, areas for improvement, and lesson strengths. The effect evaluation was conducted by using the General Liniair Model (repeated measure). The research (-design) was a pre-experimental design with pre-and post-test. Results No class or sex differences were detected among the pupils with regard to the assessment of content, methodology, and qualification of the lessons. Post-testing showed that participating pupils obtained an increased knowledge of drugs, their drug-resisting skills were enhanced, and behavior determinants (attitude, subjective norm, self-efficacy, and intention) became more negative towards drugs. Conclusions From the results of the test implementation can be cautiously concluded that the program “Study without Drugs” may yield positive results when applied in schools). Thus, this pilot program can be considered a step towards the development and implementation of an evidence-based school-oriented program for pupils in Suriname. PMID:24920468

2014-01-01

339

Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics  

PubMed Central

Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

2014-01-01

340

Prescription drug misuse, illicit drug use, and their potential risk and protective correlates in a Hispanic college student sample.  

PubMed

Illicit substance use has increased in Hispanics. Recent trends also warrant focus on prescription drug misuse, given its increased prevalence among college students. The aims of this study were to assess prescription drug misuse and illicit drug use in Hispanic students, as well as potential theoretically and empirically based risk and protective factors. Hispanic students (n = 435; 59% female) from a U.S. university located on the border with México completed a sociodemographic survey, licit, illicit, and prescription drug use frequency questionnaires, an attitudes and beliefs about prescription drugs survey, the Short Acculturation Scale for Hispanics, the Depression, Anxiety, and Stress Scales, the Collectivist Coping Styles Measure, and the Multidimensional Scale of Perceived Social Support. A hierarchical logistic regression assessed prescription drug misuse predictors including demographics, licit/illicit substance use, attitudes toward prescription drug use, acculturation, distress symptoms, coping style, perceived social support, and the interaction between distress symptoms and acculturation. A negative binomial regression assessed predictors of past 30-day illegal drug use (the same predictors as the previous model except illicit drug use). Results indicated that positive attitudes toward prescription drugs, higher anxiety, and lower depressive symptomatology increased the odds of prescription drug misuse. Past 30-day alcohol use, positive attitudes toward prescription drugs, and higher acculturation predicted past 30-day illicit drug use. Prescription drug misuse was differentially associated with distress symptoms, whereas the convergence model of acculturation was supported regarding illegal drug use. Inconsistent with hypotheses, protective factors were not significantly associated with substance use. PMID:23750694

Cabriales, José Alonso; Cooper, Theodore V; Taylor, Thom

2013-06-01

341

Variable Wing Sweep Positions  

NASA Technical Reports Server (NTRS)

Navy combat air patrol aircraft model, tested at Langley, shows two extreme positions of variable-sweep wing. This is one of the important LaRC-derived generic test configurations that defined the advantages of the outboard pivot location for variable sweep, and provided the breakthrough required for recent applications of the concept. Photograph published in Winds of Change, 75th Anniversary NASA publication (page 131) and Crafting Flight (page 66) by James Schultz.

1963-01-01

342

Obese women show greater delay discounting than healthy-weight women  

Microsoft Academic Search

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

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

2008-01-01

343

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 babies who ... HIV/AIDS Click here to learn more about effects of specific drugs . VIDEO: Why Are Drugs So Hard to Quit? ...

344

Drugs Approved for Rhabdomyosarcoma  

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

345

Computer Integrated Drug Prevention  

Microsoft Academic Search

Drug prevention education provides an important first line of defense against future drug use. Many drug prevention strategies have been developed which teach youngsters of all ages how to say no to drugs. Nevertheless, the problem of drug use and abuse continues to escalate, and younger children, particularly those undergoing harsh psychosocial stress (e.g., hunger, lack of housing, broken homes,

Michael Gropper; Zvi Liraz; David Portowicz; Mickey Schindler

1996-01-01

346

Effects of drugs on mucus clearance.  

PubMed

Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which is a quaternary ammonium compound, has been suggested to decrease CC significantly. Bromhexine, ambroxol and neutral saline seemed not to alter CC, either positively or negatively. Finally, treatment with either amiloride, recombinant human deoxyribonuclease, bromhexine, ambroxol, N-acetylcysteine, S-carboxymethylcysteine or hypertonic saline has been suggested as a possible cause of clinical improvement in patients, such as the experience of dyspnoea, the case of expectoration or the frequency of infective exacerbations. Other agents did not show a clinical benefit. PMID:10515429

Houtmeyers, E; Gosselink, R; Gayan-Ramirez, G; Decramer, M

1999-08-01

347

Drug induced rhabdomyolysis  

PubMed Central

Rhabdomyolysis is a clinical condition of potential life threatening destruction of skeletal muscle caused by diverse mechanisms including drugs and toxins. Given the fact that structurally not related compounds cause an identical phenotype pinpoints to common targets or pathways, responsible for executing rhabdomyolysis. A drop in myoplasmic ATP paralleled with sustained elevations in cytosolic Ca2+ concentration represents a common signature of rhabdomyolysis. Interestingly, cardiac tissue is hardly affected or only secondary, as a consequence of imbalance in electrolytes or acid–base equilibrium. This dogma is now impaired by compounds, which show up with combined toxicity in heart and skeletal muscle. In this review, cases of rhabdomyolysis with novel recently approved drugs will be explored for new target mechanisms in the light of previously described pathomechanisms. PMID:22560920

Hohenegger, Martin

2012-01-01

348

Hydroxylation of diclofenac: an illustration of the complementary roles of biomimetic metalloporphyrin catalysts and yeasts expressing human cytochromes P450 in drug metabolism studies  

Microsoft Academic Search

Preparative hydroxylation of aromatic compounds such as drugs remain a difficult challenge. Here we show that the two main human metabolites of the anti-inflammatory drug diclofenac, 5-hydroxy- and 4?-hydroxy-diclofenac, can be prepared from diclofenac in high yields by using two complementary model systems for human cytochromes P450. The former, which results from hydroxylation of the most reactive aromatic position of

Samya Othman; Virginie Mansuy-Mouries; Claude Bensoussan; Pierrette Battioni; Daniel Mansuy

2000-01-01

349

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

Federal Register 2010, 2011, 2012, 2013, 2014

...of the CCF, the new drug analytes MDMA, MDA, and MDEA are added, as are ``[Delta...confirmed positive drug test for MDMA, MDA, or MDEA, as appropriate, to the MRO...box--must write in the specific MDMA, MDA, or MDEA analyte in the...

2010-09-27

350

21 CFR 1301.37 - Order to show cause.  

Code of Federal Regulations, 2010 CFR

...Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND DISPENSERS OF CONTROLLED SUBSTANCES Action on Application for Registration: Revocation Or Suspension of Registration §...

2010-04-01

351

21 CFR 1301.37 - Order to show cause.  

Code of Federal Regulations, 2014 CFR

...Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND DISPENSERS OF CONTROLLED SUBSTANCES Action on Application for Registration: Revocation Or Suspension of Registration §...

2014-04-01

352

21 CFR 1301.37 - Order to show cause.  

Code of Federal Regulations, 2012 CFR

...Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND DISPENSERS OF CONTROLLED SUBSTANCES Action on Application for Registration: Revocation Or Suspension of Registration §...

2012-04-01

353

21 CFR 1301.37 - Order to show cause.  

Code of Federal Regulations, 2011 CFR

...Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND DISPENSERS OF CONTROLLED SUBSTANCES Action on Application for Registration: Revocation Or Suspension of Registration §...

2011-04-01

354

21 CFR 1301.37 - Order to show cause.  

Code of Federal Regulations, 2013 CFR

...Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND DISPENSERS OF CONTROLLED SUBSTANCES Action on Application for Registration: Revocation Or Suspension of Registration §...

2013-04-01

355

Drug Overdose Deaths, Hospitalizations,  

E-print Network

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

MacAdam, Keith

356

Postmarket Drug Safety Information  

MedlinePLUS

... postmarket drug safety information to improve transparency and communication to patients and healthcare providers. Studies and Clinical Trials of ... Safety Information Index to Drug-Specific Information For ... News & Events Includes drug safety announcements from CDER ...

357

Drug Retention Times  

SciTech Connect

The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

Center for Human Reliability Studies

2007-05-01

358

Drug Retention Times  

SciTech Connect

The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

Center for Human Reliability Studies

2007-05-01

359

Prescription Drug Abuse  

MedlinePLUS

... more dangerous than people think. In fact, it's drug abuse. And it's just as illegal as taking street ... on the street like other illegal drugs. Prescription drug abuse continues to rise. In 2012, 24% of teens ...

360

Drug-induced hepatitis  

MedlinePLUS

Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

361

Position Measurements Obeying Momentum Conservation  

E-print Network

We present a hitherto unknown fundamental limitation to a basic measurement: that of the position of a quantum object when the total momentum of the object and apparatus is conserved. This result extends the famous Wigner-Araki-Yanase (WAY) theorem, and shows that accurate position measurements are only practically feasible if there is a large momentum uncertainty in the apparatus.

Paul Busch; Leon Loveridge

2010-05-04

362

Nano-advantage in enhanced drug delivery with biodegradable nanoparticles: contribution of reduced clearance.  

PubMed

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

Kadam, Rajendra S; Bourne, David W A; Kompella, Uday B

2012-07-01

363

Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance  

PubMed Central

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

Kadam, Rajendra S.; Bourne, David W. A.

2012-01-01

364

Experimental and Mathematical Studies on the Drug Release Properties of Aspirin Loaded Chitosan Nanoparticles  

PubMed Central

The study of drug release dynamic is aiming at understanding the process that drugs release in human body and its dynamic characteristics. It is of great significance since these characteristics are closely related to the dose, dosage form, and effect of the drugs. The Noyes-Whitney function is used to represent how the solid material is dissolved into solution, and it is well used in study of drug dynamic. In this research, aspirin (acetylsalicylic acid (ASA)) has been encapsulated with different grades of chitosan (CS) varying in molecular weight (Mw) for the purpose of controlled release. The encapsulation was accomplished by ionic gelation technology based on assembly of positively charged chitosan and negatively charged sodium tripolyphosphate (TPP). The encapsulation efficiency, loading capacity, and drug release behavior of aspirin loaded chitosan nanoparticles (CS-NPs) were studied. It was found that the concentration of TPP and Aspirin, molecular weights of chitosan have important effect on the drug release patterns from chitosan nanoparticles. The results for simulation studies show that the Noyes-Whitney equation can be successfully used to interpret the drug release characteristics reflected by our experimental data. PMID:24987696

Wan, Ajun; Shi, Yifei; Zhang, Yueyue; Chen, Yupeng

2014-01-01

365

Ferromagnetic seeding for the magnetic targeting of drugs and radiation in capillary beds  

NASA Astrophysics Data System (ADS)

A new implant assisted-magnetic drug targeting approach is introduced and theoretically analyzed to demonstrate its feasibility. This approach uses ferromagnetic particles as seeds for collecting magnetic drug carrier particles at the desired site in the body, such as in a capillary bed near a tumor. Based on the capture cross section ( ?c) approach, a parametric study was carried out using a 2-D mathematical model to reveal the effects of the magnetic field strength ( ?0H0=0.01-1.0 T), magnetic drug carrier particle radius ( Rp=20-500 nm), magnetic drug carrier particle ferromagnetic material content ( xfm,p=20-80 wt%), average blood velocity ( uB=0.05-1.0 cm/s), seed radius ( Rs=100-2000 nm), number of seeds ( Ns=1-8), seed separation ( h=0-8 Rs), and magnetic drug carrier particle and seed ferromagnetic material saturation magnetizations (iron, SS 409, magnetite, and SS 304) on the performance of the system. Increasing the magnetic field strength, magnetic drug carrier particle size, seed size, magnetic drug carrier particle ferromagnetic material content, or magnetic drug carrier particle or seed saturation magnetization, all positively and significantly affected ?c, while increasing the average blood velocity adversely affected it. Increasing the number of seeds or decreasing the seed separation, with both causing less significant increases in ?c, verified that cooperative magnetic effects exist between the seeds that enhance the performance. Overall, these theoretical results were encouraging as they showed the viability of this minimally invasive, implant assisted-magnetic drug targeting approach for targeting drugs or radiation in capillary beds.

Avilés, Misael O.; Ebner, Armin D.; Ritter, James A.

2007-03-01

366

Polymers influencing transportability profile of drug  

PubMed Central

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

Gaikwad, Vinod L.; Bhatia, Manish S.

2013-01-01

367

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

PubMed Central

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

Strickland, Justin C.; Smith, Mark A.

2014-01-01

368

The Impact of Reverse Trendelenburg Versus Head-up Position on Intraoperative Bleeding of Elective Rhinoplasty  

PubMed Central

Background: In spite of several efforts for decreasing blood loss, our experience sometimes shows that some patients bleed more profusely during rhinoplasty. Patient position could have deep impact on bleeding amount during surgical procedures. Objective: In this study, we aimed to compare reverse trendelenburg position and head-up position on intra-operative bleeding of elective rhinoplasty. This was to check the effects of reverse trendelenburg position and head up position on the intraoperative bleeding of elective rhinoplasty. Methods: In this study, 30 ASA I (American Society of Anesthesiology physical condition classification) patients between 18 and 40 years of age who were candidate to rhinoplasty operations for first time were included. Patients were randomly assigned to reverse trendelenburg or head-up position. Exclusion criteria was any history or lab indicating coagulation problems or using any drug. All gauzes used and the blood that accumulated in the aspirator throughout the operation were calculated. Results: Our results showed that the mean amount of blood loss in reverse trendelenburg was lower (77.00 ± 13.20 ml) than head-up position (83.33 ± 21.18 ml), although, there was no statistical difference between two groups. However, there was no significant differences among two groups in different aspects of hemodynamic determinants and bleeding amount during and after rhinoplasty. Conclusions: Our results showed that patient bleeding is not increased because of positioning per se. In conclusion, perhaps in the future reverse trendelenburg will be given more often during rhinoplasry. PMID:24498500

Nooraei, Navid; Dabbagh, Ali; Niazi, Feizolah; Mohammadi, Siamak; Mohajerani, Seyed Amir; Radmand, Golnar; Hashemian, Seyed Mohammad Reza

2013-01-01

369

In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer's disease  

PubMed Central

Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects. Aims The aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate. Methods and materials Physico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis. Result and discussion Quercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was ?8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score ?7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity. Conclusion This in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this compound in future. PMID:24563598

Islam, Md. Rezaul; Zaman, Aubhishek; Jahan, Iffat; Chakravorty, Rajib; Chakraborty, Sajib

2013-01-01

370

Diagnosing Dementia—Positive Signs  

MedlinePLUS

... Navigation Bar Home Current Issue Past Issues Diagnosing Dementia—Positive Signs Past Issues / Fall 2007 Table of ... easy, affordable blood test that could accurately diagnose Alzheimer's disease (AD)—even before symptoms began to show? Researchers ...

371

Positive position control of robotic manipulators  

NASA Technical Reports Server (NTRS)

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

Baz, A.; Gumusel, L.

1989-01-01

372

Talent Show Notes from the Office  

E-print Network

Highlights Paintball Talent Show Notes from the Office Spring B Places of Origin Birthdays's Weekly. Talent Show ­ Tryouts We're so excited about the Talent Show! We have a long list of students, March 24. This is also the last day to sign up to be in the Talent Show. We also need a Master

Pilyugin, Sergei S.

373

Psychological distress and quality of life in drug-using and non-drug-using HIV-infected women  

Microsoft Academic Search

Background: Quantitative research on women infected with human Immunodeficiency virus (HIV) has predominantly invoked drug users. The present study assessed the psychosodal burden of HIV infection and identified some possible determinants in both drug-using and non-drug-using women. Method: Twenty-three hard-drug-using and 55 non-using HIV-positive women aged 18-64 years participated. Psychological distress (SCL-90, with eight scales and total score) and health-related

MIEKE J. E. TE; ERNA A. GAAL

374

Empowering Women? The Oprah Winfrey Show  

Microsoft Academic Search

The Oprah Winfrey Show, the most-watched US daytime talk show, aims to empower women. This article examines the show's representations of gender and how images of `race', sexuality and class cross-cut them. It considers the show's status as television psychology. It explores the show's translation of aspects of black feminism to television, and discusses the social implications of its `super-real'

Corinne Squire

1994-01-01

375

Computer-Assisted Instruction: What the Research Shows.  

ERIC Educational Resources Information Center

Briefly reviews current research on the effectiveness of computer-assisted instruction (CAI) and microcomputers. The Hawthorne Effect and research results for elementary, secondary, and college level students are discussed, courseware requirements are described, and research studies showing positive and negative effects of CAI are listed. (LRW)

Bracey, Gerald W.

1987-01-01

376

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

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

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

377

41. VIEW LOOKING IN TANK, SHOWING TRAINING DURING ASCENT (WEARING ...  

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

41. VIEW LOOKING IN TANK, SHOWING TRAINING DURING ASCENT (WEARING STEINKE HOOD) AT RIGHT, DIVING INSTRUCTOR AT LEFT MAINTAINING HIS POSITION ON THE WIRE No date - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

378

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

379

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

380

Analysis of plethysmographic waveform changes induced by beach chair positioning under general anesthesia.  

PubMed

During shoulder surgery, patients typically are placed in the beach chair position. In rare cases, this positioning has resulted in devastating outcomes of postoperative cerebral ischemia (Cullen and Kirby in APSF Newsl 22(2):25-27, 2007; Munis in APSF Newsl 22(4):82-83, 2008). This study presents a method to noninvasively and continuously hemodynamically monitor patients during beach chair positioning by using the photoplethysmograph signal recorded from a commercial pulse oximeter. Twenty-nine adults undergoing shoulder surgery were monitored before and after beach chair positioning with electrocardiogram, intermittent blood pressure, end tidal carbon dioxide, and photoplethysmograph via Nellcor finger pulse oximeter. Fast Fourier transform (FFT) was used to perform frequency-domain analysis on the photoplethysmograph (PPG) signal for data segments taken 80-120 s before and after beach chair positioning. The amplitude density of respiration-associated PPG oscillations was quantified measuring the height of the FFT peak at respiratory frequency. Results were reported as (median, interquartile range) and statistical analysis was performed using Wilcoxon sign rank test. Data were also collected when vasoactive drugs phenylephrine and ephedrine were used to maintain acceptable mean arterial pressure during a case. With beach chair positioning, all subjects who did not receive vasoactive drugs showed an increase in the FFT amplitude density of respiration-associated PPG oscillations (p < 0.0001) without change in pulse-associated PPG oscillations. The PPG was more accurate at monitoring the change to beach chair position than blood pressure or heart rate. With vasoactive drugs, pulse-associated PPG oscillations decreased only with phenylephrine while respiration-associated oscillations did not change. Frequency domain analysis of the PPG signal may be a better tool than traditional noninvasive hemodynamic parameters at monitoring patients during beach chair position surgery. PMID:24420341

Zhu, Richard; Atteya, Gourg; Shelley, Kirk H; Silverman, David G; Alian, Aymen A

2014-12-01

381

POSITION TITLE: PROMOTIONS ASSISTANT POSITION SUMMARY  

E-print Network

of branding SFU Rec, promoting programs and services, and creating a welcoming environment towards them. Excellent organizational, interpersonal, and communication skills (written & verbal: PROMOTIONS ASSISTANT POSITION SUMMARY This volunteer position is an essential part of branding SFU Rec

382

The development of multiple drug use among anabolic-androgenic steroid users: six subjective case reports  

PubMed Central

Background The inappropriate use of anabolic androgenic steroids (AAS) was originally a problem among athletes but AAS are now often used in nonsport situations and by patients attending regular addiction clinics. The aim of this study was to improve understanding of the development of multiple drug use in patients seeking treatment at an addiction clinic for AAS-related problems. Methods We interviewed six patients (four men and two women) with experience of AAS use who were attending an addiction clinic for what they believed were AAS-related problems. The patients were interviewed in-depth about their life stories, with special emphasis on social background, substance use, the development of total drug use and subjective experienced psychological and physical side effects. Results There was significant variation in the development of drug use in relation to social background, onset of drug use, relationship to AAS use and experience of AAS effects. All patients had initially experienced positive effects from AAS but, over time, the negative experiences had outweighed the positive effects. All patients were dedicated to excess training and took AAS in combination with gym training, indicating that the use of these drugs is closely related to this form of training. Use of multiple drugs was common either in parallel with AAS use or serially. Conclusion The study shows the importance of understanding how AAS use can develop either with or without the concomitant use of other drugs of abuse. The use of AAS can, however, progress to the use of other drugs. The study also indicates the importance of obtaining accurate, comprehensive information about the development of AAS use in designing treatment programmes and prevention strategies in this area. PMID:19040748

Skårberg, Kurt; Nyberg, Fred; Engström, Ingemar

2008-01-01

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

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

MedlinePLUS

... Images Flu Prevention Toolkit Influenza Types Seasonal Avian Swine Variant Pandemic Other Get Email Updates To receive ... antivirals/summary-clinicians.htm . Influenza Types Seasonal Avian Swine Variant Pandemic Other Get Email Updates To receive ...

385

Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistance.  

PubMed

Quorum sensing (QS) is a bacterial communication process that depends on the bacterial population density. It involves small diffusible signaling molecules which activate the expression of myriad genes that control diverse array of functions like bioluminescence, virulence, biofilm formation, sporulation, to name a few. Since QS is responsible for virulence in the clinically relevant bacteria, inhibition of QS appears to be a promising strategy to control these pathogenic bacteria. With indiscriminate use of antibiotics, there has been an alarming increase in the number of antibiotic resistant pathogens. Antibiotics are no longer the magic bullets they were once thought to be and therefore there is a need for development of new antibiotics and/or other novel strategies to combat the infections caused by multidrug resistant organisms. Quorum sensing inhibition or quorum quenching has been pursued as one of such novel strategies. While antibiotics kill or slow down the growth of bacteria, quorum sensing inhibitors (QSIs) or quorum quenchers (QQs) attenuate bacterial virulence. A large body of work on QS has been carried out in deadly pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio fischeri, V. harveyi, Escherichia coli and V. cholerae etc to unravel the mechanisms of QS as well as identify and study QSIs. This review describes various aspects of QS, QSI, different model systems to study these phenomena and recent patents on various QSIs. It suggests QSIs as attractive alternatives for controlling human, animal and plant pathogens and their utility in agriculture and other industries. PMID:23394143

Bhardwaj, Ashima K; Vinothkumar, Kittappa; Rajpara, Neha

2013-04-01

386

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

PubMed

The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (?-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively.Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions.Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative. PMID:25590496

Delaveris, Gerd Jorunn Møller; Hoff-Olsen, Per; Rogde, Sidsel

2015-03-01

387

New Hampshire Guide 4-H Dog Shows  

E-print Network

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

New Hampshire, University of

388

Prevalence of extended-spectrum ?-lactamase positive bacteria in radiologically positive urinary tract infection.  

PubMed

The increase in antibiotic resistance among uropathogens is a global problem. The present study was an effort to assess the current antibiotic resistance pattern and plasmid profiles of some multi drug resistant bacteria isolated from urinary tract infection (UTI). Among 44 clinical samples of radiologically positive UTI, 44 microorganisms belonging to 9 genus were isolated. Of the patients, 24 were female and 20 were male. Highest incidence was found in age group of 30-45 years. Total bacterial count of the urine samples were high in most the patients. E. coli and coagulase-negative Staphylococcus spp. were most prevalent. Most of the isolates showed higher antibiotic resistance against the antibiotics used. 6 of the 44 isolate was resistant to 10 different types of antibiotics. Of the isolated uropathogens, 40.9% were ESBL positive. 7 of the isolates had no plasmid and 9 isolate had 140 MDa plasmid whereas other isolates pose smaller plasmids of different sizes. Assessment of transfer of antibiotic resistance between different genuses revealed transfer of resistance within genus. Radiological imaging showed strong correlation with microbiological findings of the patients. PMID:24839589

Masud, Md Rana; Afroz, Hafsa; Fakruddin, Md

2014-01-01

389

Do initial responses to drugs predict future use or abuse?  

PubMed Central

DE WIT, H., T.J. Phillips. Do initial responses to drugs predict future use or abuse? Individuals vary in their initial reactions to drugs of abuse, in ways that may contribute to the likelihood of subsequent drug use. In humans, most drugs of abuse produce positive subjective states such as euphoria and feelings of wellbeing, which may facilitate repeated use. In nonhumans, many drugs initially increase locomotor activity and produce discriminative stimulus effects, both of which have been considered to be models of human stimulant and subjective states. Both humans and nonhumans vary in their sensitivity to early acute drug effects, in ways that may predict future use or self-administration, and some of these variations appear to be genetic in origin. However, it is not known exactly how the initial responses to drugs in either humans or nonhumans relate to subsequent use or abuse. In humans, positive effects of drugs facilitate continued use of a drug while negative effects discourage use, and in nonhumans, greater genetic risk for drug intake is predicted by reduced sensitivity to drug aversive effects; but whether these initial responses affect escalation of drug use, and the development of dependence is currently unknown. Although early use of a drug is a necessary step in the progression to abuse and dependence, other variables may be of greater importance in the transition from use to abuse. Alternatively, the same variables that predict initial acute drug effects and early use may significantly contribute to continued use, escalation and dependence. Here we review the existing evidence for relations between initial direct drug effects, early use, and continued use. Ultimately, these relations can only be determined from systematic longitudinal studies with comprehensive assessments from early drug responses, to progression of problem drug use. In parallel, additional investigation of initial responses in animal models as predictors of drug use will shed light on the underlying mechanisms. PMID:22542906

Phillips, Tamara J.

2012-01-01

390

Drug Discovery Prospect from Untapped Species: Indications from Approved Natural Product Drugs  

PubMed Central

Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery. PMID:22808057

Qin, Chu; Tao, Lin; Liu, Xin; Shi, Zhe; Zhang, Cun Long; Tan, Chun Yan; Chen, Yu Zong; Jiang, Yu Yang

2012-01-01

391

Drug Delivery by Tattooing to Treat Cutaneous Leishmaniasis  

PubMed Central

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

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

2014-01-01

392

Inside Gun Shows What Goes On  

E-print Network

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

Leistikow, Bruce N.

393

Inside Gun Shows What Goes On  

E-print Network

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

Nguyen, Danh

394

Inside Gun Shows What Goes On  

E-print Network

Gun Shows Work Buying and Selling What's for Sale Culture Politics Interventions v 1 11 55 91 159 219Preface Inside Gun Shows What Goes On When Everybody Thinks Nobody's Watching #12;#12;Inside Gun-Violence Effort. She put gun shows on my radar and is an ace straw-purchase spotter. Thanks also to Barbara Claire

Leistikow, Bruce N.

395

Graphing Current Drug Data  

NSDL National Science Digital Library

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

396

discoveries in drugs and  

E-print Network

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

Glasser, Benjamin J.

397

Drugs and Young People  

MedlinePLUS

Drug abuse is a serious public health problem.It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

398

Inheritance and Drug Response  

Microsoft Academic Search

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

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

2003-01-01

399

ETHICS AND DRUG RESISTANCE  

Microsoft Academic Search

ABSTRACTThis paper reviews the dynamics behind, and ethical issues associated with, the phenomenon of drug resistance. Drug resistance is an important ethical issue partly because of the severe consequences likely to result from the increase in drug resistant pathogens if more is not done to control them. Drug resistance is also an ethical issue because, rather than being a mere

MICHAEL J. SELGELID

2007-01-01

400

Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy.  

PubMed

There is wide variability in the response of individuals to standard doses of drug therapy. This is an important problem in clinical practice, where it can lead to therapeutic failures or adverse drug events. Polymorphisms in genes coding for metabolizing enzymes and drug transporters can affect drug efficacy and toxicity. Pharmacogenomics aims to identify individuals predisposed to high risk of toxicity and low response from standard doses of anticancer drugs. This chapter focuses on the clinical significance of polymorphisms in drug-metabolizing enzymes and drug transporters in influencing efficacy and toxicity of anticancer therapy. The most important examples to demonstrate the influence of pharmacogenomics on anticancer therapy are thiopurine methyltransferase (TPMT), UGT (uridine diphosphate glucuronosyltransferase) 1A1*28, and DPD (dihydropyrimidine dehydrogenase) *2A, respectively, for 6-mercaptopurine, irinotecan, and 5-fluorouracil therapy. However, in most other anticancer therapies no clear association has been found for polymorphisms in drug-metabolizing enzymes and drug transporters and pharmacokinetics or pharmacodynamics of anticancer drugs. Evaluation of different regimens and tumor types showed that polymorphisms can have different, sometimes even contradictory, pharmacokinetic and pharmacodynamic effects in different tumors in response to different drugs. The clinical application of pharmacogenomics in cancer treatment therefore requires more detailed information regarding the different polymorphisms in drug-metabolizing enzymes and drug transporters. A greater understanding of complexities in pharmacogenomics is needed before individualized therapy can be applied on a routine basis. PMID:18370231

Bosch, Tessa M

2008-01-01

401

Novel central nervous system drug delivery systems.  

PubMed

For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

2014-05-01

402

Black Youths and Illegal Drugs.  

ERIC Educational Resources Information Center

Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug

Joseph, Janice; Pearson, Patricia G.

2002-01-01

403

Implicit and Explicit Drug-Related Cognitions during Detoxification Treatment are Associated with Drug Relapse: An Ecological Momentary Assessment Study  

PubMed Central

Objective Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments (EMA), we examined whether craving and cognitions assessed during drug detoxification treatment were associated with relapse. Method Participants were 68 heroin-dependent inpatients undergoing clinical detoxification at an addiction treatment center. Participants carried around a personal digital assistant (PDA) for 1-week. Participants completed up to 4 random assessments (RAs) per day. They also completed an assessment when they experienced a temptation to use drugs (TA). At each assessment, participants reported their craving and attitudes to drugs. Implicit cognitions were assessed with a drug Stroop task (attentional bias) and an Implicit Association Test (implicit attitudes). Results Individuals who relapsed during the study week exhibited a larger attentional bias and more positive implicit attitudes to drugs than non-relapsers at TAs (but not RAs). In addition, compared to non-relapsers, relapsers reported higher levels of craving and more positive explicit attitudes to drugs at TAs compared to RAs. Additional within-subject analyses revealed that attentional bias for drugs at TAs increased before relapse. Conclusions Drug-related cognitive processes assessed using EMA were associated with relapse during drug detoxification. Real-time assessment of craving and cognitions may help to identify individuals at risk of relapse, and when they are at risk of relapse. PMID:23231572

Marhe, Reshmi; Waters, Andrew J.; van de Wetering, Ben J. M.; Franken, Ingmar H. A.

2012-01-01

404

[Drug residues in food fish].  

PubMed

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

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

1990-07-01

405

Rethinking drug policy: an integrity preserving compromise position  

E-print Network

of LSD (lysergic acid diethylamide) has been available since the 1950?s, widespread use has been curtailed by strict controls on LSD?s precursor chemical, ergotamine tartrate. Pure LSD is not generally found on the streets because its chemicals...

Crispino, Azzurra

2006-10-30

406

Smart drugs: green shuttle or real drug?  

PubMed

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

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

2013-11-01

407

Drug Absorption Principles  

Microsoft Academic Search

Pharmacokinetics describes drug absorption, distribution, metabolism, and excretion processes. Absorption is the rate and\\u000a extent at which drugs reach the systemic circulation from the site of administration. Distribution of a drug includes all\\u000a the processes that are involved from the time when the drug reaches the circulation to the time when it (or a metabolite of\\u000a the drug) leaves the

Xianhua Cao; Lawrence X. Yu; Duxin Sun

408

Antibody-drug conjugate (ADC) clinical pipeline: a review.  

PubMed

Biological therapies play an increasing role in cancer treatment, although the number of naked antibodies showing clinical efficacy as single agent remains limited. One way to enhance therapeutic potential of antibodies is to conjugate them to small molecule drugs. This combination is expected to bring together the benefits of highly potent drugs on the one hand and selective binders of specific tumor antigens on the other hand. However, designing an ADC is more complex than a simple meccano game, requiring thoughtful combination of antibody, linker, and drugs in the context of a target and a defined cancer indication. Lessons learned from the first-generation antibody-drug conjugate (ADC) and improvement of the technology guided the design of improved compounds which are now in clinical trials. Brentuximab vedotin (Adcetris(®)), an anti-CD30 antibody conjugated to a potent microtubule inhibitor for the treatment of Hodgkin's lymphoma and anaplastic large cell lymphomas, is the only marketed ADC today. A total of 27 ADC are currently undergoing clinical trials in both hematological malignancies and solid tumor indications. Among them, T-DM1 (trastuzumab emtansine), an ADC comprised of trastuzumab conjugated to DM1, via a non-cleavable linker, is showing very promising results in phase III for the treatment of HER2-positive refractory/relapsed metastatic breast cancer. Other compounds, such as CMC-544, SAR3419, CDX-011, PSMA-ADC, BT-062, and IMGN901 currently in clinical trials, targeting varied antigens and bearing different linker and drugs, contribute to the learning curve of ADC, as do the discontinued ADC. Current challenges include improvement of the therapeutic index, linked to a careful selection of the targets, a better understanding of ADC mechanism of action, the management and understanding of ADC off-target toxicities, as well as the selection of appropriate clinical settings (patient selection, dosing regimen) where these molecules can bring highest clinical benefit. PMID:23913138

Sassoon, Ingrid; Blanc, Véronique

2013-01-01

409

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.

410

Effective drug delivery by PEGylated drug conjugates  

Microsoft Academic Search

The current review presents an update of drug delivery using poly(ethylene glycol) (PEG), that focuses on recent developments in both protein and organic drugs. Certainly the past 10 years has resulted in a renaissance of the field of PEG drug conjugates, initiated by the use of higher molecular weight PEGs (Mw>20,000), especially 40,000 which is estimated to have a plasma

Richard B. Greenwald; Yun H. Choe; Jeffrey McGuire; Charles D. Conover

2003-01-01

411

Diabetes Drug Metformin Safe for Patients with Kidney Disease: Review  

MedlinePLUS

... JavaScript. Diabetes Drug Metformin Safe for Patients With Kidney Disease: Review Alternative medications more costly, have more side ... medication, is usually not prescribed for people with kidney disease, a new analysis shows the drug may be ...

412

Psychedelic Drug Flashbacks: Psychotic Manifestation or Imaginative Role Playing?  

ERIC Educational Resources Information Center

Examines possible differences in psychopathological characteristics among flashbackers, nonflashback drug users, and nondrug user controls. Results indicate that flashbackers show no more general maladjustment than the nonflashback drug users. (Author)

Matefy, Robert E.; Krall, Roger

1975-01-01

413

Positive basis for surface skein algebras.  

PubMed

We show that the twisted SL2 skein algebra of a surface has a natural basis (the bracelets basis) that is positive, in the sense that the structure constants for multiplication are positive integers. PMID:24982193

Thurston, Dylan Paul

2014-07-01

414

The Physics of Equestrian Show Jumping  

ERIC Educational Resources Information Center

This article discusses the kinematics and dynamics of equestrian show jumping. For some time I have attended a series of show jumping events at Spruce Meadows, an international equestrian center near Calgary, Alberta, often referred to as the "Wimbledon of equestrian jumping." I have always had a desire to write an article such as this…

Stinner, Art

2014-01-01

415

Salton Sea Satellite Image Showing Fault Slip  

USGS Multimedia Gallery

Landsat satellite image (LE70390372003084EDC00) showing location of surface slip triggered along faults in the greater Salton Trough area. Red bars show the generalized location of 2010 surface slip along faults in the central Salton Trough and many additional faults in the southwestern section of t...

416

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

417

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.

418

Livestock Shows Quick Reference Health Requirements  

E-print Network

15 MARKET STEER INFO Knoxville Spring Junior Cattle Exposition Ownership Deadline: March 1 Tattooed Deadline: 90 days prior to show Tattooed and Ear Tagged: 90 days prior to show Entries Due to UT: May 1 INFO Knoxville Spring Junior Cattle Exposition Ownership Deadline: March 15 Tattooed and Ear Tagged

Grissino-Mayer, Henri D.

419

Artificial Nucleosome Positioning Sequences  

NASA Astrophysics Data System (ADS)

We have used the emerging rules for the sequence dependence of DNA bendability to design and test a series of DNA molecules that incorporate strongly into nucleosomes. Competitive reconstitution experiments showed the superiority in histone octamer binding of DNA molecules in which segments consisting exclusively of A and T or G and C, separated by 2 base pairs (bp), are repeated with a 10-bp period. These repeated (A/T)3NN(G/C)3NN motifs are superior in nucleosome formation to natural positioning sequences and to other repeated motifs such as AANNNTTNNN and GGNNNCCNNN. Studies of different lengths of repetitive anisotropically flexible DNA showed that a segment of ? 40 bp embedded in a 160-bp fragment is sufficient to generate nucleosome binding equivalent to that of natural nucleosome positioning sequences from 5S RNA genes. Bending requirements along the surface of the nucleosome seem to be quite constant, with no large jumps in binding free energy attributable to protein-induced kinks. The most favorable sequences incorporate into nucleosomes more strongly by 100-fold than bulk nucleosomal DNA, but differential bending free energies are small when normalized to the number of bends: a free energy difference of only about 100 cal/mol per bend (1 cal = 4.184 J) distinguishes the best bending sequences and bulk DNA. We infer that the distortion energy of DNA bending in the nucleosome is only weakly dependent on DNA sequence.

Shrader, Thomas E.; Crothers, Donald M.

1989-10-01

420

Planetary Positions on Medieval Maps  

Microsoft Academic Search

A RECENT issue (Feb. 27) of the Illustrated London News contained a reproduction of an old map believed to have been used, and possibly drawn, by Columbus. At the side of the world map is a map showing the celestial `spheres' according to the Ptolemaic system. It is of special interest because it shows the positions * of the heavenly

Duncan MacNaughton

1932-01-01

421

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 of ...

422

Drug-induced esophageal strictures.  

PubMed Central

A retrospective study of 55 patients with a benign esophageal stricture showed that in 11 patients (20%) the cause was a drug-induced lesion due to potassium chloride (3), tetracyclines (3), aspirin (2), vitamin C (1), phenytoin (1), and quinidine (1). Five of the 11 patients would have been diagnosed as having a reflux etiology of their stricture if 24-hour esophageal pH monitoring was not performed. Six patients responded to dilatation and five patients required resection or bypass. A prospective study of 18 asymptomatic volunteers showed a high incidence of esophageal lodgment of a radiolabeled medicinal capsule, with subsequent dissolution and release of the isotope. This occurred most frequently in elderly subjects and was reduced by increasing the volume of water chaser. The sites of lodgment correspond to the location of the observed strictures in the patient population. An in vitro study showed that, when the causative drugs were mixed with saliva, dissolution occurred within 60 minutes and was associated with significant changes in pH. These investigations show that drug-induced esophageal strictures are more common than previously appreciated, and can be confused with a reflux etiology. Diagnosis is suggested by a history of drug ingestion, location of the stricture, and a normal esophageal acid exposure on 24-hour pH monitoring. The severity of the esophageal injury is variable and requires dilatation to resection for therapy. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:3606243

Bonavina, L; DeMeester, T R; McChesney, L; Schwizer, W; Albertucci, M; Bailey, R T

1987-01-01

423

Antiarrhythmic drug selection.  

PubMed

The selection of an effective and well-tolerated antiarrhythmic drug requires a systematic approach. Two methods for evaluating drug effect are routinely used--noninvasive techniques involving monitoring and exercise testing, and an invasive approach utilizing electrophysiologic testing. Each method has strengths and weaknesses and they must be applied to the appropriate patient. The evaluation of drug effect involves two types of testing. The acute drug test is a rapid screening of drug action, while a short-term maintenance period confirms drug efficacy and permits exposure of side effects. One of the most serious toxic effects is drug-induced aggravation of arrhythmia. An additional benefit of a systematized protocol is the identification of several effective agents that may be administered in combination to enhance antiarrhythmic drug effect. If an effective and well-tolerated drug is prescribed, recurrent malignant arrhythmia can be prevented. PMID:3555284

Podrid, P J

1987-01-01

424

Religion and drug use by adolescents  

Microsoft Academic Search

Introduction Many international studies show that religion is an important dimension modulating the use of alcohol and drugs by adolescents. Objectives: to determine which religious variables are associated to frequent or heavy use of alcohol, tobacco and drugs among adolescents in inter- mediate and high schools in Campinas, Brazil. Methods: A cross-sectional study using a self-report anonymous questionnaire was administered

Paulo Dalgalarrondo; Meire Aparecida Soldera

2004-01-01

425

Toward a Rational View of Hallucinogenic Drugs.  

ERIC Educational Resources Information Center

The enactment of California's "LSD Bill" is presented as an example of poor judgment in drug legislation on the state level. An appraisal of the nonmedical use of hallucinogens centering around the types of users, and the results of drug use, shows that the principal social impact of hallucinogens is on the personalities and values of the users.…

McGlothlin, William H.

426

Drug and Alcohol Arrests Increased in 1999.  

ERIC Educational Resources Information Center

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

Nicklin, Julie L.

2001-01-01

427

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

428

Systems that prevent unwanted represcription of drugs withdrawn because of adverse drug events: a systematic review  

PubMed Central

Represcription of medication that was withdrawn after the occurrence of an adverse drug event (including allergy), is a recognized medication safety issue on a patient level. We performed a systematic review to identify systems (electronic and nonelectronic) that can prevent the represcription of drugs withdrawn because of an adverse drug event and the effects of these systems. The review was performed using PRISMA and Cochrane guidelines. PubMed and Embase were searched for articles describing systems that can prevent represcription of drugs that had been withdrawn for causing an adverse drug event. Information on the characteristics of the studies, systems, and if present results achieved with such systems, was extracted. The results showed that of 6793 articles screened, 137 full-text articles were assessed for eligibility. A total of 45 studies describing 33 systems (28 electronic) were included. The five nonelectronic systems used allergy bracelets or allergy labels on hospital medical records or on drug orders. Systems differed in the way adverse drug events were documented and how users were alerted to drug represcription. Most systems functioned within a specific healthcare setting. Of 12 studies that compared pre- and post-intervention periods or wards with and without intervention, 7 showed a reduction in represcription after adverse drug event. In conclusion, several systems have been developed that can prevent the represcription of drugs that elicited an adverse drug event, but the evidence that these systems are effective is limited. PMID:25083253

Jansen, Paul A.F.; Grouls, René J.E.; van Marum, Rob J.; Verberne, Marianne A.J.W.; Aussems, Lieke M.A.; Egberts, Toine C.G.; Korsten, Erik H.M.

2013-01-01

429

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

PubMed

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

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

2014-06-01

430

Scientific issues in drug testing: council on scientific affairs  

SciTech Connect

Testing for drugs in biologic fluids, especially urine, is a practice that has become widespread. The technology of testing for drugs in urine has greatly improved in recent years. Inexpensive screening techniques are not sufficiently accurate for forensic testing standards, which must be met wihen a person's employment or reputation may be affected by results. This is particularly a concern during screening of a population in which the prevalence of drug use is very low, in which the predictive value of a positive result would be quite low. Physicians should be aware that results from drug testing can yield accurate evidence of prior exposure to drugs, but they do not provide information about patterns of drug use, about abuse of or dependence on drugs, or about mental or physical impairments that may result from drug use.

Not Available

1987-06-12

431

Bayesian active learning for drug combinations.  

PubMed

The dynamics of complex diseases are governed by intricate interactions of myriad factors. Drug combinations, formed by mixing several single-drug treatments at various doses, can enhance the effectiveness of the therapy by targeting multiple contributing factors. The main challenge in designing drug combinations is the highly nonlinear interaction of the constituent drugs. Prior work focused on guided space-exploratory heuristics that require discretization of drug doses. While being more efficient than random sampling, these methods are impractical if the drug space is high dimensional or if the drug sensitivity is unknown. Furthermore, the effectiveness of the obtained combinations may decrease if the resolution of the discretization grid is not sufficiently fine. In this paper, we model the biological system response to a continuous combination of drug doses by a Gaussian process (GP). We perform closed-loop experiments that rely on the expected improvement criterion to efficiently guide the exploration process toward drug combinations with the optimal response. When computing the criterion, we marginalize out the GP hyperparameters in a fully Bayesian manner using a particle filter. Finally, we employ a hybrid Monte Carlo algorithm to rapidly explore the high-dimensional continuous search space. We demonstrate the effectiveness of our approach on a fully factorial Drosophila dataset, an antiviral drug dataset for Herpes simplex virus type 1, and simulated human Apoptosis networks. The results show that our approach significantly reduces the number of required trials compared to existing methods. PMID:23846437

Park, Mijung; Nassar, Marcel; Vikalo, Haris

2013-11-01

432

Drug repositioning: playing dirty to kill pain.  

PubMed

The number of approved new molecular entity drugs has been decreasing as the pharmaceutical company investment in research and development is increasing. As we face this painful crisis, called an innovation gap, there is increasing awareness that development of new uses of existing drugs may be a powerful tool to help overcome this obstacle because it takes too long, costs too much and can be risky to release drugs developed de novo. Consequently, drug repositioning is emerging in different therapeutic areas, including the pain research area. Worldwide, pain is the main reason for seeking healthcare, and pain relief represents an unmet global clinical need. Therefore, development of analgesics with better efficacy, safety and cost effectiveness is of paramount importance. Despite the remarkable advancement in research on cellular and molecular mechanisms underlying pain pathophysiology over the past three decades, target-based therapeutic opportunities have not been pursued to the same extent. Phenotypic screening remains a more powerful tool for drug development than target-based screening so far. It sounds somewhat heretical, but some multi-action drugs, rather than very selective ones, have been developed intentionally. In the present review, we first critically discuss the utility of drug repositioning for analgesic drug development and then show examples of 'old' drugs that have been successfully repositioned or that are under investigation for their analgesic actions. We conclude that drug repositioning should be more strongly encouraged to help build a bridge between basic research and pain relief worldwide. PMID:24327258

Bastos, Leandro Francisco Silva; Coelho, Márcio Matos

2014-01-01

433

Transplant Problems That May Show Up Later  

MedlinePLUS

... soon after transplant Next Topic Other transplant issues Transplant problems that may show up later The type ... called Second Cancers Caused by Cancer Treatment . Post-transplant lymphoproliferative disorder Post-transplant lymphoproliferative ( lim -fo-pruh- ...

434

Do dogs (Canis familiaris) show contagious yawning?  

PubMed

We report an experimental investigation into whether domesticated dogs display contagious yawning. Fifteen dogs were shown video clips of (1) humans and (2) dogs displaying yawns and open-mouth expressions (not yawns) to investigate whether dogs showed contagious yawning to either of these social stimuli. Only one dog performed significantly more yawns during or shortly after viewing yawning videos than to the open-mouth videos, and most of these yawns occurred to the human videos. No dogs showed significantly more yawning to the open-mouth videos (human or dog). The percentage of dogs showing contagious yawning was less than chimpanzees and humans showing this behavior, and considerably less than a recently published report investigating this behavior in dogs (Joly-Mascheroni et al. in Biol Lett 4:446-448, 2008). PMID:19452178

Harr, Aimee L; Gilbert, Valerie R; Phillips, Kimberley A

2009-11-01

435

Nutrition and Feeding of Show Poultry  

E-print Network

The championship potential of a chicken or turkey is determined by genetics, but proper nutrition can help an animal achieve that genetic potential. This publication outlines four principles critical to developing a nutrition program for show...

Cartwright, A. Lee

2003-11-03

436

Perceived Need for Treatment among Drug Using Arrestees in Four Cities.  

ERIC Educational Resources Information Center

Explores the need for drug-abuse treatment among drug-using arrestees in four U.S. cities. Results show that 30% to 55% of drug-using arrestees perceived a need for treatment. Explains that the most important predictors for perceived need for treatment are previous experience with drug treatment, having previously injected a drug, and having no…

Sabin, Edward P.

1998-01-01

437

10. POWELL STREET RECONSTRUCTION: Photocopy of October 1971 photograph showing ...  

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

10. POWELL STREET RECONSTRUCTION: Photocopy of October 1971 photograph showing a Powell-type yoke in place in the street. Photo taken on Powell Street near Ellis during repair work on the conduit. Note brick work of original 1887 conduit walls, and position of the slot rails, track rails, and cable in relationship to the yokes. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

438

Positive Classroom Environments = Positive Academic Results  

ERIC Educational Resources Information Center

This article discusses the effects of a positive classroom environment and its impact on student behavior and achievement. It also provides strategies for developing expectations for student achievement and the importance of parental involvement. A positive classroom environment is essential in keeping behavior problems to a minimum. There are a…

Wilson-Fleming, LaTerra; Wilson-Younger, Dylinda

2012-01-01

439

Want Positive Behavior? Use Positive Language  

ERIC Educational Resources Information Center

Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

Wood, Chip; Freeman-Loftis, Babs

2012-01-01

440

Capillary electrophoresis for drug analysis  

NASA Astrophysics Data System (ADS)

Capillary electrophoresis (CE) is a high resolution separation technique which is amenable to a wide variety of solutes, including compounds which are thermally degradable, non-volatile and highly polar, and is therefore well suited for drug analysis. Techniques which have been used in our laboratory include electrokinetic chromatography (ECC), free zone electrophoresis (CZE) and capillary electrochromatography (CEC). ECC, which uses a charged run buffer additive which migrates counter to osmotic flow, is excellent for many applications, including, drug screening and analyses of heroin, cocaine and methamphetamine samples. ECC approaches include the use of micelles and charged cyclodextrins, which allow for the separation of complex mixtures. Simultaneous separation of acidic, neutral and basic solutes and the resolution of optical isomers and positional isomers are possible. CZE has been used for the analysis of small ions (cations and anions) in heroin exhibits. For the ECC and CZE experiments performed in our laboratory, uncoated capillaries were used. In contrast, CEC uses capillaries packed with high performance liquid chromatography stationary phases, and offers both high peak capacities and unique selectivities. Applications include the analysis of cannabinoids and drug screening. Although CE suffers from limited concentration sensitivity, it is still applicable to trace analysis of drug samples, especially when using injection techniques such as stacking, or detection schemes such as laser induced fluorescence and extended pathlength UV.

Lurie, Ira S.

1999-02-01

441

Clinically relevant drug interactions with antiepileptic drugs  

PubMed Central

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

Perucca, Emilio

2006-01-01

442

Adverse drug reactions in veterinary patients associated with drug transporters.  

PubMed

For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

Mealey, Katrina L

2013-09-01

443

Adverse drug events in hospital: pilot study with trigger tool  

PubMed Central

OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension. PMID:24626548

Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia

2013-01-01

444

Antiplatelet and Anticoagulant Drugs in Interventional Radiology  

SciTech Connect

In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

Altenburg, Alexander; Haage, Patrick, E-mail: patrick.haage@helios-kliniken.de [University Hospital Witten/Herdecke, Department of Diagnostic and Interventional Radiology, HELIOS Klinikum Wuppertal (Germany)

2012-02-15

445

Thalidomide Shows Activity Against AIDS-Related Kaposi's Sarcoma  

Cancer.gov

The drug thalidomide, used in the 1950s and 1960s as a sedative which led to birth defects in newborns of mothers who took the drug, has now been shown to have clinical activity against Kaposi's sarcoma (KS).

446

Ask Your Pharmacist Generic Drugs  

E-print Network

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

447

[Endocrine effects of antiepileptic drugs].  

PubMed

Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was reported to enhance leptin and insulin blood level and increased body weight, whereas topiramate showed an opposite effect. In contrast to thyroid and gonadal hormones, only a few data concern antiepileptic drug action in HPA axis. To this end, no effect of antiepileptic drugs on adrenocorticotropic hormone (ACTH)/cortisol circadian rhytmicity was found. Valproate decreased CRH release in rats, whereas lamotrigine stabilized ACTH/cortisol secretion. Moreover, felbamate was found to inhibit stress-induced corticosterone release in mice. Interestingly, recent data suggest that felbamat and some other new antiepileptic drugs may inhibit transcriptional activity of glucocorticoid receptors. Summing up, the above data suggest that traditional antiepileptic drugs may cause endocrine disturbances, especially in gonadal hormones. PMID:19205363

Le?kiewicz, Monika; Budziszewska, Bogus?awa; Laso?, W?adys?aw

2008-01-01