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1

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

2

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

3

[Incretin mimetic drugs: therapeutic positioning].  

PubMed

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

López Simarro, F

2014-07-01

4

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

PubMed

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

Gramel, Sabine

2005-01-01

5

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

6

Bed Position Matters for Stroke Patients, Report Shows  

MedlinePLUS

... page, please enable JavaScript. Bed Position Matters for Stroke Patients, Report Shows But clear guidelines aren't ... Preidt Thursday, November 6, 2014 Related MedlinePlus Page Stroke THURSDAY, Nov. 6, 2014 (HealthDay News) -- Hospital bed ...

7

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 kids be at risk for substance abuse? Families strive to find the best ways to ...

8

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.

9

Subcutaneous trastuzumab: drug development and current position.  

PubMed

HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use. PMID:24777594

Martín Martorell, P; Bermejo de Las Heras, B; Pérez-Fidalgo, J A; Huerta Alvaro, M; Martín, M; Albanell, J; Lluch Hernández, A

2014-10-01

10

Targeted Drug for Melanoma Shows Promise in Early Clinical Testing  

Cancer.gov

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

11

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.

12

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.

13

Rethinking drug policy: an integrity preserving compromise position  

E-print Network

The "War on Drugs" has been raging for twenty years without resolution. This work attempts to provide a compromise position between the prohibitionists and the legalizers that preserves the integrity of both positions. This compromise position...

Crispino, Azzurra

2006-10-30

14

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.

15

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.

16

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.

17

National Survey Shows Lower Rate of Illicit Drug Use among Adolescents Ages 12 to 17  

MedlinePLUS

... illicit drug use among adolescents ages 12 to 17 Report also shows continued lower rates of current ... and binge drinking among those aged 12 to 17 Tuesday, September 16, 2014 The rate of current ( ...

18

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

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

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

19

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

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

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

20

Positive Urgency Predicts Illegal Drug Use and Risky Sexual Behavior  

PubMed Central

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

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

2009-01-01

21

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

PubMed Central

Safer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50-60,000 people each year. Here we report that fexinidazole, a drug currently in phase I clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg kg?1) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC99 value for at least 24h following a single oral dose. A once daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of visceral leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat visceral leishmaniasis. In African trypanosomes, the mode of action of nitro-drugs involves reductive activation via an NADH-dependent bacterial-like nitroreductase. Overexpression of the leishmanial homologue of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating visceral leishmaniasis. PMID:22301556

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

2012-01-01

22

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

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

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

23

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

Cancer.gov

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

24

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

PubMed

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, CO, from 2000 through 2004 using targeted sampling. The sample was primarily men, White (48%), 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 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

2009-09-01

25

Drugs developed for treatment of diabetes show protective effects in Alzheimer's and Parkinson's diseases.  

PubMed

Type 2 diabetes has been identified as a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). In the brains of patients with AD and PD, insulin signaling is impaired. This finding has motivated new research that showed good effects using drugs that initially had been developed to treat diabetes. Preclinical studies showed good neuroprotective effects applying insulin or long lasting analogues of incretin peptides. In transgenic animal models of AD or PD, analogues of the incretin GLP-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality and reduced the symptoms of the diseases. Amyloid plaque load and synaptic loss as well as cognitive impairment had been prevented in transgenic AD mouse models, and dopaminergic loss of transmission and motor function has been reversed in animal models of PD. On the basis of these promising findings, several clinical trials are being conducted with the first encouraging clinical results already published. In several pilot studies in AD patients, the nasal application of insulin showed encouraging effects on cognition and biomarkers. A pilot study in PD patients testing a GLP-1 receptor agonist that is currently on the market as a treatment for type 2 diabetes (exendin-4, Byetta) also showed encouraging effects. Several other clinical trials are currently ongoing in AD patients, testing another GLP-1 analogue that is on the market (liraglutide, Victoza). Recently, a third GLP-1 receptor agonist has been brought to the market in Europe (Lixisenatide, Lyxumia), which also shows very promising neuroprotective effects. This review will summarise the range of these protective effects that those drugs have demonstrated. GLP-1 analogues show promise in providing novel treatments that may be protective or even regenerative in AD and PD, something that no current drug does. PMID:25331995

Hölscher, Christian

2014-10-25

26

Phosphaturic mesenchymal tumors show positive staining for somatostatin receptor 2A (SSTR2A).  

PubMed

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome associated with tumors that secrete phosphaturic hormones, most notably fibroblast growth factor 23 (FGF23). The majority of tumors associated with this syndrome show stereotypical histological features and are now known as phosphaturic mesenchymal tumors (PMTs). We postulated that immunohistochemistry for somatostatin receptor 2A (SSTR2A) could be used to definitively identify PMTs or other tumors that cause TIO. Immunohistochemistry for FGF23 and SSTR2A was performed on 15 tumors from 14 patients with a definite diagnosis of TIO. All showed positive staining for both markers. While FGF23 staining was quite focal in some tumors, SSTR2A showed diffuse strong expression. In 40 control tumors not known to be associated with the clinical or biochemical features of TIO, FGF23 expression was found in 2 cases (one aneurysmal bone cyst and one osteosarcoma). SSTR2A expression was found in 9 control tumors (4 synovial sarcomas, 2 hemangiomas, 2 aneurysmal bone cysts and one osteosarcoma). Only one tumor (an aneurysmal bone cyst) showed positive staining for both FGF23 and SSTR2A. SSTR2A also commonly stained neoplastic and non-neoplastic endothelial cells. We conclude that neither FGF23 nor SSTR2A expression are specific for the diagnosis of PMT. However both stains are highly sensitive. Because of its diffuse strong expression and widespread availability, immunohistochemistry for SSTR2A is useful to confirm the diagnosis of PMT in an appropriate setting particularly if material is limited. Negative staining can serve as an excellent rule out test for this diagnosis. PMID:24060005

Houang, Michelle; Clarkson, Adele; Sioson, Loretta; Elston, Marianne S; Clifton-Bligh, Roderick J; Dray, Michael; Ranchere-Vince, Dominique; Decouvelaere, Anne-Valerie; de la Fouchardiere, Arnaud; Gill, Anthony J

2013-12-01

27

Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimer's disease.  

PubMed

Type 2 diabetes is a risk factor for developing Alzheimer's disease (AD). In the brains of AD patients, insulin signalling is desensitised. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and analogues such as liraglutide are on the market as treatments for type 2 diabetes. We have previously shown that liraglutide showed neuroprotective effects in the APPswe/PS1?E9 mouse model of AD. Here, we test the GLP-1 receptor agonist lixisenatide in the same mouse model and compare the effects to liraglutide. After ten weeks of daily i.p. injections with liraglutide (2.5 or 25 nmol/kg) or lixisenatide (1 or 10 nmol/kg) or saline of APP/PS1 mice at an age when amyloid plaques had already formed, performance in an object recognition task was improved in APP/PS1 mice by both drugs at all doses tested. When analysing synaptic plasticity in the hippocampus, LTP was strongly increased in APP/PS1 mice by either drug. Lixisenatide (1 nmol/kg) was most effective. The reduction of synapse numbers seen in APP/PS1 mice was prevented by the drugs. The amyloid plaque load and dense-core Congo red positive plaque load in the cortex was reduced by both drugs at all doses. The chronic inflammation response (microglial activation) was also reduced by all treatments. The results demonstrate that the GLP-1 receptor agonists liraglutide and lixisenatide which are on the market as treatments for type 2 diabetes show promise as potential drug treatments of AD. Lixisenatide was equally effective at a lower dose compared to liraglutide in some of the parameters measured. PMID:25107586

McClean, Paula L; Hölscher, Christian

2014-11-01

28

Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli  

PubMed Central

Prior neuroimaging studies support the hypothesis that anticipation, an important component of anxiety, may be mediated by activation within the insular and medial prefrontal cortices including the anterior cingulate cortex. However, there is an insufficient understanding of how affective anticipation differs across anxiety groups in emotional brain loci and networks. We examined 14 anxiety positive (AP) and 14 anxiety normative (AN) individuals completing an affective picture anticipation task during functional magnetic resonance imaging (fMRI). Brain activation was examined across groups for cued anticipation (to aversive or pleasant stimuli). Both groups showed greater activation in the bilateral anterior insula during cued differential anticipation (i.e., aversive vs. pleasant) and activation on the right was significantly higher in AP compared to AN subjects. Functional connectivity showed that the left anterior insula was involved in a similar network during pleasant anticipation in both groups. The left anterior insula during aversive and the right anterior insula during all anticipation conditions co-activated with a cortical network consisting of frontal and parietal lobes in the AP group to a greater degree. These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psychiatric traits. PMID:21181800

Simmons, Alan; Stein, Murray B.; Strigo, Irina A; Arce, Estibaliz; Hitchcock, Carla; Paulus, Martin P.

2011-01-01

29

Zinc-positive boutons in the cerebral cortex of lizards show glutamate immunoreactivity  

Microsoft Academic Search

Summary Zinc-positive boutons, originating in the medial cortex of lizards, exhibit glutamate immunoreactivity. This finding supports the presumed homology between lizard zinc-positive boutons and the hippocampal mossy fibres of mammals, which are also glutamate-immunoreactive and zinc-positive.

F. J. Martinez-Guijarro; E. Soriano; J. A. Del Rio; C. Lopez-Garcia

1991-01-01

30

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

MedlinePLUS

... Lupus in Mice A drug delivery system using nanoparticle technology that allows for better targeting of specific ... be effectively programmed to seek specific cells. Although nanoparticle drug delivery systems have been used experimentally to ...

31

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

Microsoft Academic Search

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

Steven Grant; Carlo Contoreggi; Edythe D. London

2000-01-01

32

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

NSDL National Science Digital Library

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

APS Communications Office (American Physiological Society Communications Office)

2006-04-17

33

Pregnancy outcome among HIV positive and negative intravenous drug users  

Microsoft Academic Search

Objective: To analyze determinants of pregnancy outcome, among HIV infected and uninfected intravenous drug users. Study design: A total of 315 pregnant current intravenous drug users, IVDU (151 HIV infected and 164 HIV uninfected subjects) were referred to the Center for Pregnant Drug Addicts of the Mangiagalli Clinic, Milan, Italy, for internatal care and delivery between 1985 and 1993. Results:

Anna Bucceri; Laura Luchini; Laura Rancilio; Emilio Grossi; Gabriele Ferraris; Gabriele Rossi; Mario Vignali; Fabio Parazzini

1997-01-01

34

Positive and negative aspects of participation in illicit drug research: Implications for recruitment and ethical conduct  

Microsoft Academic Search

Improved understanding of incentives and barriers to drug user research participation may improve study recruitment, retention and outcomes and enhance the ethical acceptability of illicit drug research. In Melbourne, Australia during 2001–2004, 507 injecting drug users were recruited from Needle and Syringe Programs and asked to nominate the ‘best’ and ‘worst’ things about research. Commonly reported positive aspects of drug

Monica J. Barratt; Josephine S. Norman; Craig L. Fry

2007-01-01

35

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

PubMed Central

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

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

2013-01-01

36

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

Cancer.gov

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

37

Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity  

Microsoft Academic Search

Background: Drugs can induce different immunologic reactions; T-cell mediated responses produce the most severe reactions. Although in vitro studies show that T cells recognize drugs or their metabolites and induce an effector cytotoxic response, direct in vivo evidence of involvement is lacking. T lymphocytes produce cytotoxic markers that are responsible for 2 major pathways to cell death: granule-mediated exocytosis (perforin

Sinforiano J. Posadas; Antonia Padial; Maria J. Torres; Cristobalina Mayorga; Laura Leyva; Elena Sanchez; Javier Alvarez; Antonino Romano; Carlos Juarez; Miguel Blanca

2002-01-01

38

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.

39

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.

40

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

41

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.

42

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

PubMed

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

Sams-Dodd, Frank

2007-04-01

43

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

ERIC Educational Resources Information Center

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

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

2005-01-01

44

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.

45

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.

46

Differences in treatment outcome between male alcohol dependent offenders of domestic violence with and without positive drug screens.  

PubMed

Men who are violent toward their partners tend to have a dual problem with alcohol and drug use, yet little is known about differences between men with single rather than dual problems. This study was one of the first to evaluate differences between alcohol dependent men who were arrested for Intimate Partner Violence (IPV) with and without concurrent illicit drug use. Seventy-eight participants were randomly assigned to manual-guided group behavioral therapies (Cognitive Behavioral Therapy or Twelve Step Facilitation) and assessed across 12 weeks of treatment. Despite denying drug use at baseline, thirty-two clients (43%) tested positive for illicit drug use (cocaine and marijuana) during the 12 weeks of treatment. The study specifically addressed whether there were differences between clients using alcohol only versus individuals using both alcohol + drugs in terms of 1) baseline characteristics; 2) treatment compliance (e.g., attendance and substance use during treatment; and 3) treatment outcomes (alcohol, drug use, anger management, and aggression at the completion of treatment). The results showed that there were comparatively few differences between the alcohol versus the alcohol + drug using groups at baseline. Regarding treatment compliance and retention, alcohol + drug using participants attended significantly fewer sessions, had significantly fewer percent days abstinence from alcohol use, significantly more total days of positive breathalyzer results. Regarding treatment outcomes across anger management and aggression scores, the alcohol + drug using participants had significantly more impairments in anger management styles from pre- to post-treatment. However, there were no differences between the groups across verbal or physical aggression. Both groups improved in their verbal aggression from pre- to post-treatment. The findings suggest that alcohol dependent men who continue to use illicit drugs may require additional interventions to effectively control their drug use and, their anger management styles. PMID:17367953

Easton, Caroline J; Mandel, Dolores; Babuscio, Theresa; Rounsaville, Bruce J; Carroll, Kathleen M

2007-10-01

47

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

48

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

49

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.

50

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

51

Risk behaviours among HIV positive injecting drug users in Myanmar: a case control study  

PubMed Central

Background The severity of HIV/AIDS pandemic linked to injecting drug use is one of the most worrying medical and social problems throughout the world in recent years. Myanmar has one of the highest prevalence rates of HIV among the IDUs in the region. Aim The objective of the study was to determine the risk behaviours among HIV positive injecting drug users in Myanmar. Methods A non matched case control study was conducted among 217 respondents registered with a non governmental organization's harm reduction center. 78 HIV positive IDUs were used as cases and 139 non HIV positive IDUs as controls. The study was conducted between April-May 2009. Data was analysed using SPSS version 15 and the study was ethically conducted. Results Factors like age, marital status, age first used drugs, drug use expenditure, reason for drug use, age first used injection were found to be significant. Other risk factors found significantly associated with HIV among IDU were education (OR 2.3), location of respondent (OR 2.4) type of syringe first used (OR 5.1), sharing syringe at the first injection (OR 4.5) and failure of drug detoxification programme (OR 4.9). More HIV positive IDUs were returning used syringes in the centre (OR 3.3). Conclusions Prudent measures such as access to sterile syringes and continuous health education programmes among IDUs and their sexual partners are required to reduce high risk behaviours of IDUs in Myanmar. PMID:20515507

2010-01-01

52

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

PubMed Central

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

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

2013-01-01

53

Gender, Drug Use, and Perceived Social Support Among HIV Positive Patients  

Microsoft Academic Search

We investigated the relationships among gender, drug use, and perceived social support in 176 HIV positive patients recruited\\u000a with their informal caregivers in HIV clinics. Perceived caregiver support, emotional support, tangible support, and conflict\\u000a were assessed. Current drug use was defined as heroin and\\/or cocaine use within 6 months prior to baseline. Gender was not\\u000a significantly associated with any of the

Gabriella Rothman; Bradley J. Anderson; Michael D. Stein

2008-01-01

54

Positive predictive values of abused drug immunoassays on the Beckman Synchron in a veteran population.  

PubMed

The pressure to reduce the cost of analytic testing makes it tempting to discontinue routine confirmation of urine specimens positive for drugs of abuse by immunoassay. Beyond the economic motivation, the requirement for confirmation should be driven by the positive predictive value of the screening tests. We have quantitated positive predictive values of our screening immunoassays in a large metropolitan Veterans Affairs Medical Center. We reviewed the confirmatory rate of urine specimens positive for drugs of abuse with Beckman Synchron reagents from June 1998 to June 1999 and tabulated the false-positive screening rate. There were 175 instances of false-positive screens during the 13 months we analyzed. Positive predictive values ranged from 0% (amphetamine) to 100% (THC). We determined that the low positive predictive value of the amphetamine assay in our laboratory was primarily due to the use of ranitidine (Zantac). Urine specimens containing greater than 43 microg/mL ranitidine were positive in our amphetamine assay. This concentration is routinely exceeded in our patients taking ranitidine. In our clinical and analytic setting, the Beckman THC assay did not require confirmation. The positive predictive values of the Beckman opiate, cocaine, barbiturate, propoxyphene, and methadone immunoassays dictate routine confirmatory testing in specimens that screen positive for these substances. Finally, because of its extreme sensitivity to ranitidine, the Beckman amphetamine assay has little utility in our laboratory setting. PMID:11327349

Dietzen, D J; Ecos, K; Friedman, D; Beason, S

2001-04-01

55

OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer.  

PubMed

The RANK/RANKL/OPG pathway is well known for bone destruction in skeletal metastases but has also been implicated in osteoclast-independent roles in tumorigenesis and de novo metastasis. Experimental data suggest contribution of progesterone to tumorigenesis may be mediated by RANKL. Importantly, modulation of this pathway became possible through the availability of denosumab, an artificial counterpart of OPG, but significant gaps remain in the translation of preclinical findings on the pathway. We analyzed gene expression of RANK, RANKL and OPG from 40 Affymetrix datasets encompassing 4467 primary breast cancers and focused on ER positive disease. We did not observe a significant prognostic value of RANK and RANKL mRNA expression. In contrast, OPG was associated with a better prognosis among 1941 ER positive cancers (HR 0.64, 95% CI 0.53-0.77; P < 0.0001) using a cutoff from its highly bimodal expression. We detected considerable heterogeneity regarding the prognostic value of OPG between different datasets. This heterogeneity could neither be attributed to technical reasons nor to differences in standard clinical parameters or treatments of the cohorts. Interestingly, the prognostic value of the progesterone receptor and of OPG showed similar cohort specific effects. Still both factors were no surrogates for each other but contributed independent prognostic value in multivariate analyses. Thus, both OPG and PgR are independently associated with good prognosis in ER positive breast cancer. However both markers share common cohort specific differences in contrast to proliferation markers as Ki67 which may be based on the underlying biology. PMID:24785095

Sänger, Nicole; Ruckhäberle, Eugen; Bianchini, Giampaolo; Heinrich, Tomas; Milde-Langosch, Karin; Müller, Volkmar; Rody, Achim; Solomayer, Erich Franz; Fehm, Tanja; Holtrich, Uwe; Becker, Sven; Karn, Thomas

2014-10-01

56

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

ERIC Educational Resources Information Center

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

Guthmann, Debra S.; Sandberg, Katherine A.

57

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

Microsoft Academic Search

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

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

2006-01-01

58

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

PubMed

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

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

2011-03-18

59

Stress processes in HIV-positive African American mothers: Moderating effects of drug abuse history  

Microsoft Academic Search

This study examined the mechanism by which stressors, dissatisfaction with family, perceived control, social support, and coping were related to psychological distress in a sample of HIV-positive African American mothers. Additional analyses explored whether women who had a history of a drug abuse or dependence diagnosis differed either on levels of the study variables or the model pathways. The results

Myron J. Burns; Daniel J. Feaster; Victoria B. Mitrani; Christina Ow; José Szapocznik

2008-01-01

60

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

PubMed Central

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

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

2012-01-01

61

[SICI-GISE position paper on drug-coated balloon use in the coronary district].  

PubMed

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogeneous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjunctive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. At present, a variety of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian Society of Interventional Cardiology (SICI-GISE) decided to coordinate the efforts of a group of renowned experts in this field, in order to produce a position paper on the correct use of drug-coated balloons in all settings of coronary artery disease, giving a class of indication to each one, based on clinical evidence. This position paper represents a quick reference for operators, investigators and manufacturers to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice. PMID:24121894

Cortese, Bernardo; Sgueglia, Gregory A; Berti, Sergio; Biondi-Zoccai, Giuseppe; Colombo, Antonio; Limbruno, Ugo; Bedogni, Francesco; Cremonesi, Alberto

2013-10-01

62

An allosteric modulator of HIV-1 protease shows equipotent inhibition of wild-type and drug-resistant proteases.  

PubMed

NMR and MD simulations have demonstrated that the flaps of HIV-1 protease (HIV-1p) adopt a range of conformations that are coupled with its enzymatic activity. Previously, a model was created for an allosteric site located between the flap and the core of HIV-1p, called the Eye site (Biopolymers 2008, 89, 643-652). Here, results from our first study were combined with a ligand-based, lead-hopping method to identify a novel compound (NIT). NIT inhibits HIV-1p, independent of the presence of an active-site inhibitor such as pepstatin A. Assays showed that NIT acts on an allosteric site other than the dimerization interface. MD simulations of the ligand-protein complex show that NIT stably binds in the Eye site and restricts the flaps. That bound state of NIT is consistent with a crystal structure of similar fragments bound in the Eye site (Chem. Biol. Drug Des. 2010, 75, 257-268). Most importantly, NIT is equally potent against wild-type and a multidrug-resistant mutant of HIV-1p, which highlights the promise of allosteric inhibitors circumventing existing clinical resistance. PMID:25062388

Ung, Peter M-U; Dunbar, James B; Gestwicki, Jason E; Carlson, Heather A

2014-08-14

63

Thirsty heroin addicts show different fMRI activations when exposed to water-related and drug-related cues.  

PubMed

Relapse to drug use is frequently preceded or caused by craving, an intense desire for drug. Advances in functional brain imaging techniques make it possible to directly investigate this special mental state in vivo and non-invasively. Extant imaging studies on craving have been mostly on cocaine which is the dominant drug abused in the U.S. Employing functional MRI, we examined substance specificity of the neural circuitry underlying craving for heroin. Heroin is the primary drug abused in south-east Asia and has, particularly, become a serious social problem for China in recent years. Following abstinence from water and drug, 14 active heroin addicts (all male, mean age 33.2 years, average drug use history 7.1 years) underwent scanning inside a 1.5T Philips MR scanner during exposure to water-related, drug-related, and neutral cues. Water-related cues elicited anterior cingulate activation (Brodmann's area BA 32/24). Drug-related cues activated bilateral inferior frontal cortex (BA 44/45), confirming the critical role of prefrontal cortex in drug craving. Results suggest heroin craving may involve different neural substrates than do desire from basic physiological drives, such as thirst. As the first fMRI study of heroin craving, our study adds to the scant but much-needed brain imaging literature on heroin addiction. PMID:16406379

Xiao, Zhuangwei; Lee, Tatia; Zhang, John X; Wu, Qiulin; Wu, Renhua; Weng, Xuchu; Hu, Xiaoping

2006-06-28

64

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

PubMed

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

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

2012-08-01

65

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

PubMed Central

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

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

2012-01-01

66

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

PubMed Central

In a herd of 20 sheep in Sweden, a country where brucellosis has never been diagnosed in sheep or goats, a total of six sheep were found serologically positive to Brucella melitensis in two different rounds of sampling. Yersinia enterocolitica serotype O:9 could at the time of the second sampling be isolated from four sheep, one of them at the same time serologically positive for B. melitensis. The article describes the case and gives some background information on brucellosis and Y. enterocolitica in general as well as a more specific description of the Swedish surveillance program for B. melitensis and the test procedures used. The problem with false-positive reactions, in particular its implications for surveillance programs in low prevalence or officially brucellosis-free countries, is discussed. PMID:23240071

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

2012-01-01

67

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

PubMed

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

Anderson, Jeffrey M

2011-07-01

68

Promotion as Prevention: Positive Youth Development as Protective against Tobacco, Alcohol, Illicit Drug, and Sex Initiation  

Microsoft Academic Search

The present study was designed to examine the association of positive youth development with the likelihood of tobacco, alcohol, marijuana, hard drug, and sex initiation between 5th and 10th grades. A national, largely middle-class sample of 5,305 adolescents, participating in a longitudinal study funded by the National 4-H Council (although not all participants were enrolled in 4-H or other after-school

Seth J. Schwartz; Erin Phelps; Jacqueline V. Lerner; Shi Huang; C. Hendricks Brown; Selva Lewin-Bizan; Yibing Li; Richard M. Lerner

2010-01-01

69

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

Cancer.gov

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

70

Efficacy and safety of anti-tuberculosis drugs in HIV-positive patients: A prospective study  

PubMed Central

Objectives: To assess the efficacy and safety of anti-tuberculosis drugs in HIV-positive patients at a tertiary care teaching hospital. Materials and Methods: As a part of an ongoing study of opportunistic infections (OIs) in HIV-positive patients, drug treatment in patients suffering from tuberculosis was assessed to determine its efficacy and safety. Based on prevalence data for last three years, a purposive sampling of study population was carried out in this observational, prospective, single centre study. Tuberculosis (TB) was the most common OI observed. The selected patients were followed up for a period of one year to evaluate the clinical course and outcome of OIs, and the efficacy and safety of drugs used was checked. Results: Tuberculosis was observed in 89 out of 134 enrolled patients. These included 79 adults and 10 children. Males (66.2%) were commonly affected. Extra pulmonary TB (73%) was the most common manifestation with abdominal TB observed in 55 (61.7%) patients. All patients were treated in accordance with the Revised National Tuberculosis Control Programme (RNTCP) guidelines as recommended by National AIDS Control Organization (NACO), India. Outcome of TB was assessable in 70 patients. Majority (82.8%) of the patients were cured, while 12 patients (17.1%) died during the course of treatment. A total of 149 ADRs were observed in 67 (75.2%) patients. Majority of ADRs (n = 147) were non-serious and did not warrant a change in therapy. Discoloration of urine was the most common ADR observed. Conclusion: TB is the most common opportunistic infection in HIV-positive patients with abdominal TB being the most common manifestation. RNTCP and NACO guidelines are adhered to in these patients. Anti-tuberculosis drugs are well tolerated and effective in majority of the patients. PMID:24130377

Kapadia, Jigar D.; Desai, Chetna K.; Solanki, Manish N.; Shah, Asha N.; Dikshit, R. K.

2013-01-01

71

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

72

Coping among HIV negative and HIV positive female injection drug users.  

PubMed

The study examined the psychosocial determinants of coping ability in a cohort of 249 HIV positive and HIV negative female injection drug users (IDUs), using a cross-sectional retrospective design. Information collected using a structured questionnaire included data on psychosocial risk and protective factors in the personality, family, and peer domains, HIV status, and coping ability. Coping ability was associated with conventionality, greater control of emotions, less psychopathology, and family cohesion in both HIV positive and HIV negative subjects. The psychosocial factors affected coping in HIV positive and HIV negative IDUs via two different mediational models. The interactional findings supported the influence of risk/protective interactions in both groups. The findings demonstrate the impact of the interplay between personality factors and external support on coping ability in female IDUs. PMID:10407459

Brook, D W; Brook, J S; Whiteman, M; Roberto, J; Masci, J R; Amundsen, F; de Catalogne, J

1999-06-01

73

Social networks and HCV viremia among anti-HCV positive rural drug users  

PubMed Central

Summary Though social networks are known to play an important role in drug-using behaviors associated with HCV infection, literature on social networks and HCV is inconsistent. This exploratory study examined HCV RNA distribution within a social network of anti-HCV positive rural Appalachia nonmedical prescription opioid users (NMPOUs). Participants were tested serologically for HCV RNA, and behavioral, demographic, and network data were collecting using interview-administered questionnaires. Multivariate analyses were performed using logistic regression. Behavioral and demographic characteristics did not differ by RNA status. In the multivariate model, recent injection drug users were more likely to be RNA-positive (OR: 4.06, 95% CI: 1.04 – 15.83), and turnover into one’s drug network was significantly protective (OR: 0.15, 95% CI: 0.03-0.75). This is the first study to date to examine HCV distribution among rural NMPOUs from a network perspective and demonstrates that network characteristics significantly contribute to the epidemiology of HCV in this understudied, high-risk population. PMID:22717190

YOUNG, A. M.; JONAS, A. B.; HAVENS, J. R.

2012-01-01

74

Loss and regeneration: influences on the reproductive decisions of HIV positive, drug-using women.  

PubMed

Current approaches to the reduction of perinatal transmission of HIV infection among drug-using women focus on the content of counseling sessions which may include suggestions to abstain from sexual intercourse, to use barrier contraceptives, or to terminate pregnancy. The broader social and cultural issues which may influence some HIV positive women's decisions to have children (such as prolonged, unwanted separation from existing children; the need for appropriate drug treatment; empowerment through educational and vocational opportunities; and the meanings associated with motherhood, children, and HIV/AIDS) are not addressed in these efforts. This study of the reproductive decisions and meanings associated with children and motherhood among drug-using, female methadone patients describes some of the social and cultural influences on reproductive decisions. The findings suggest that discontinuous mother-child coresidence; locally produced theories of perinatal transmission; and the culturally constructed meanings associated with motherhood and children influence decisions to bear children among HIV infected, drug-using women. Relevant policy issues are discussed. PMID:7877463

Pivnick, A

1994-11-01

75

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

Cancer.gov

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

76

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

PubMed Central

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

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

2002-01-01

77

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

Cancer.gov

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

78

Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients  

PubMed Central

Background Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. Methods We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. Results For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared to recommended dosages based on the level of estimated kidney function, 3% to 19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. Conclusions The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function. PMID:23963249

Okparavero, Aghogho A; Tighiouart, Hocine; Krishnasami, Zipporah; Wyatt, Christina M; Graham, Hiba; Hellinger, James; Inker, Lesley A

2014-01-01

79

Kinetic analysis shows that vitamin A disposal rate in humans is positively correlated with vitamin A stores.  

PubMed

Vitamin A (VA) kinetics, storage, and disposal rate were determined in well-nourished Chinese and U.S. adults using model-based compartmental analysis. [(2)H(8)]Retinyl acetate (8.9 micromol) was orally administered to U.S. (n = 12; 59 +/- 9 y; mean +/- SD) and Chinese adults (n = 14; 54 +/- 4 y) and serum tracer and VA concentrations were measured from 3 h to 56 d. Using the Windows version of the Simulation, Analysis and Modeling software, we determined that the average time from dosing until appearance of labeled retinol in serum was greater in U.S. subjects (40.6 +/- 8.47 h) than in Chinese subjects (32.2 +/- 5.84 h; P < 0.01). Model-predicted total traced mass (898 +/- 637 vs. 237 +/- 109 micromol), disposal rate (14.7 +/- 5.87 vs. 5.58 +/- 2.04 micromol/d), and system residence time (58.9 +/- 28.7 vs. 42.9 +/- 14.6 d) were greater in U.S. than in Chinese subjects (P < 0.05). The model-predicted VA mass and VA mass estimated by deuterated retinol dilution at 3 and 24 d did not differ. VA disposal rate was positively correlated with VA traced mass in Chinese (R(2) = 0.556), U.S. (R(2) = 0.579), and all subjects (R(2) = 0.808). Additionally, VA disposal rate was significantly correlated with serum retinol pool size (R(2) = 0.227) and retinol concentration (R(2) = 0.330) in all subjects. Our results support the hypothesis that VA stores are the principle determinant of VA disposal rate in healthy, well-nourished adults. PMID:18424609

Cifelli, Christopher J; Green, Joanne B; Wang, Zhixu; Yin, Shian; Russell, Robert M; Tang, Guangwen; Green, Michael H

2008-05-01

80

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

81

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

82

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper.  

PubMed

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity. PMID:23617635

Brockow, K; Garvey, L H; Aberer, W; Atanaskovic-Markovic, M; Barbaud, A; Bilo, M B; Bircher, A; Blanca, M; Bonadonna, B; Campi, P; Castro, E; Cernadas, J R; Chiriac, A M; Demoly, P; Grosber, M; Gooi, J; Lombardo, C; Mertes, P M; Mosbech, H; Nasser, S; Pagani, M; Ring, J; Romano, A; Scherer, K; Schnyder, B; Testi, S; Torres, M; Trautmann, A; Terreehorst, I

2013-06-01

83

Delusion of pregnancy in a drug-naďve young woman showing hyperprolactinemia and hypothyroidism: a case report.  

PubMed

The present article reports the case of a delusional pregnancy that developed in a drug-naďve young woman affected by paranoid schizophrenia and Hashimoto-related hyperprolactinemia. The literature in this field has addressed the phenomenon of distorted thoughts of pregnancy being elicited by physical changes due to drug-induced hyperprolactinemia. The present report gives account of a case of delusional pregnancy that developed in a schizophrenic patient with concurrent hyperprolactinemia induced by a primary endocrine disease. In this instance, however, amelioration of delusional beliefs did not ensue from hyperprolactinemia normalization, but was mostly due to cognitive restructuring of distorted thinking (together with the antipsychotic treatment). This finding confirms the importance of considering the key role of the interaction of biological, cognitive and psychological mechanisms in the construction of inaccurate beliefs and feelings about pregnancy. PMID:24199783

Penta, Elena; Lasalvia, Antonio

2013-01-01

84

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

E-print Network

This study compared the celebrity illegal drug overdose deaths of River Phoenix, Chris Farley, and Brad Renfro to the prescription drug overdose deaths of Anna Nicole Smith, Heath Ledger, and Brittany Murphy. This research used quantitative...

Wood, Michelle

2011-12-31

85

Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey  

Microsoft Academic Search

Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance\\u000a use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This\\u000a study examined the association between school drug testing programs and student substance use in schools with different climates.\\u000a The analysis was based on

Sharon R. SznitmanSally; Sally M. Dunlop; Priya Nalkur; Atika Khurana; Daniel Romer

86

Laser Captured Hepatocytes Show Association of BCHE Loss and Fibrosis Progression in Hepatitis C Infected Drug Users  

PubMed Central

Chronic hepatitis C virus (HCV) infection is complicated by hepatic fibrosis. Hypothesizing that early fibrogenic signals may originate in cells susceptible to HCV infection, hepatocyte gene expression was analyzed from persons with chronic HCV at different stages of liver fibrosis. Four HCV-infected subjects with pre-cirrhotic liver fibrosis (Ishak fibrosis 3–5) were matched for age, race, and gender to five HCV-infected subjects with no evidence of fibrosis (Ishak fibrosis 0). Hepatocytes from each subject were isolated from liver biopsies using laser capture microdissection. Transcriptome profiling was performed on hepatocyte RNA using hybridization arrays. We found that hepatocytes in pre-cirrhotic fibrosis were depleted for genes involved in small molecule and drug metabolism, especially butyrylcholinesterase (BCHE), a gene involved in the metabolism of drugs of abuse. Differential expression of BCHE was validated in the same tissues and cross-sectionally in an expanded cohort of 143 HCV-infected individuals. In a longitudinal study, serum BCHE activity were already decreased at study inception in 19 fibrosis progressors compared to 20 fibrosis non-progressors (p<0.05). Non-progressors also had decreased BCHE activity over time compared to initial values, but these evolved a median (range) 8.6 (7.8–11.4) years after the study period inception(p<0.05). Laser captured portal tracts were enriched for immune related genes when compared to hepatocytes but pre-cirrhotic livers lost this enrichment. Conclusion Overall, we found that chronic HCV is associated with hepatocyte BCHE loss years before hepatic synthetic function is impaired. These results indicate that BCHE may be involved in the pathogenesis of HCV-related fibrosis among injection drug users. PMID:22331678

Munshaw, Supriya; Hwang, Hyon S.; Torbenson, Michael; Quinn, Jeffrey; Hansen, Kasper D.; Astemborski, Jacquie; Mehta, Shruti H.; Ray, Stuart C.; Thomas, David L.; Balagopal, Ashwin

2012-01-01

87

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

88

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

89

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

PubMed

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

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

2013-10-01

90

Neurites undergoing Wallerian degeneration show an apoptotic-like process with annexin V positive staining and loss of mitochondrial membrane potential  

Microsoft Academic Search

Wallerian degeneration, the disintegration of the distal part of an injured axon, is an important event in many neurodegenerative diseases. We studied Wallerian degeneration in dorsal root ganglion (DRG) explants in culture by separating neurites from their cell bodies with a scalpel. The severed neurites showed Annexin V positive staining, that spreads distally with a rate comparable to that of

Caroline Sievers; Nick Platt; V. Hugh Perry; Michael P Coleman; Laura Conforti

2003-01-01

91

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

92

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

PubMed

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

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

1993-12-01

93

Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.  

PubMed

Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed. PMID:23641692

Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

2013-05-01

94

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

Code of Federal Regulations, 2011 CFR

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

2011-10-01

95

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

Code of Federal Regulations, 2013 CFR

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

2013-10-01

96

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

Code of Federal Regulations, 2012 CFR

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

2012-10-01

97

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

Code of Federal Regulations, 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

98

Novel hydrophilic drug polymer nano-conjugates of Cisplatin showing long blood retention profile: its release kinetics, cellular uptake and bio-distribution.  

PubMed

The present study evaluates the efficacy of drug polymer self folding nano-conjugates of pectin-cisplatin to enhance blood circulating levels of cisplatin. The binding of nano-conjugate was confirmed by a peak-shift in UV-spectra. Physical characterization was done by DLS and TEM. Pharmacokinetics and bio-distribution of the nano-conjugates were performed at various time points in normal, Balb-c mice. Zeta Potential showed the shielding effect on the negative potential of pectin that was approximately 7 times more than the pectin chains when conjugated with cisplatin. TEM confirmed the formation of a hydrophilic, easily re-dispersible nano-conjugate in the size range of 100 nm. Release kinetics in plasma showed that the pectin-cisplatin conjugate is a stable, slow and sustained system with no burst effect. Immuno-fluorescence analysis of J-774, a mouse macrophage cell line, was assessed after incubating the cells with pectin chains tagged with FITC as well as Pectin-Cisplatin-FITC conjugates. With the cellular uptake of these particles in J-774, 40% of the cells showed an uptake post 30 min of incubation. However, Pectin chains were clearly eliminated. The plasma proteins facilitate the release of cisplatin with 85-89% of the drug being released in 17 days, and only 57% of drug was released in approximately 30 days without plasma. The reduced negative charge on the conjugate helps in adhesion to the cell surface and subsequent uptake by cells as evidenced by cell uptake studies on J-774 cell line. Nano-conjugates showed long blood retention profile in mice and the cisplatin was found in circulation even after 24 hrs. Pharmacokinetic study clearly indicates that it can form a novel anticancer drug that possesses good efficacy and has a safer profile than cisplatin. PMID:18393814

Verma, Anita K; Sachin, K

2008-04-01

99

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

Microsoft Academic Search

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

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

2009-01-01

100

The effects of low literacy and cognitive impairment on medication adherence in HIV-positive injecting drug users  

Microsoft Academic Search

Low literacy and cognitive impairment have each been separately identified as risks for non-adherence in HIV infection. However, no studies to date have evaluated these skill deficits in combination. We therefore characterized the nature of literacy and cognitive skills in a sample of HIV-positive injecting drug users and assessed their combined effects on adherence. A community-recruited sample of 57 HIV-positive

Drenna Waldrop-Valverde; Deborah L. Jones; Stephen Weiss; Mahendra Kumar; Lisa Metsch

2008-01-01

101

Positive and negative ion mode ESI-MS and MS/MS for studying drug-DNA complexes  

NASA Astrophysics Data System (ADS)

We report systematic investigation of duplex DNA complexes with minor groove binders (Hoechsts 33258 and 33342, netropsin and DAPI) and intercalators (daunomycin, doxorubicin, actinomycin D, ethidium, cryptolepine, neocryptolepine, m-Amsacrine, proflavine, ellipticine and mitoxantrone) by ESI-MS and ESI-MS/MS in the negative ion mode and in the positive ion mode. The apparent solution phase equilibrium binding constants can be determined by measuring relative intensities in the ESI-MS spectrum. While negative ion mode gives reliable results, positive ion mode gives a systematic underestimation of the binding constants and even a complete suppression of the complexes for intercalators lacking functional groups capable of interacting in the grooves. In the second part of the paper we systematically compare MS/MS fragmentation channels and breakdown curves in the positive and the negative modes, and discuss the possible uses and caveats of MS/MS in drug-DNA complexes. In the negative mode, the drugs can be separated in three groups: (1) those that leave the complex with no net charge; (2) those that leave the complex with a negative charge; and (3) those that remain attached on the strands upon dissociation of the duplex due to their positive charge. In the positive ion mode, all complexes fragment via the loss of protonated drug. Information on the stabilization of the complex by drug-DNA noncovalent interactions can be obtained straightforwardly only in the case of neutral drug loss. In all other cases, proton affinity (in the positive ion mode), gas-phase basicity (in the negative ion mode) and coulombic repulsion are the major factors influencing the fragmentation channel and the dissociation kinetics.

Rosu, Frédéric; Pirotte, Sophie; Pauw, Edwin De; Gabelica, Valérie

2006-07-01

102

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

103

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

104

Relationship Between Antimicrobial Drug Usage and Antimicrobial Susceptibility of Gram-Positive Mastitis Pathogens  

Microsoft Academic Search

The objective of this study was to analyze relation- ships between usage of antimicrobial drugs on dairy farmsandresults ofantimicrobialsusceptibilitytesting of mastitis pathogens. Exposure to selected antimicro- bial drugs (n = 10) was standardized by calculation of the number of defined daily doses used per cow. Farms (n = 40) were categorizedbased on amount of antimicro- bial exposure: organic (no usage);

M. Pol; P. L. Ruegg

2007-01-01

105

Are You Positive? The Relationship of Minority Composition to Workplace Drug and Alcohol Testing  

Microsoft Academic Search

Although testing for alcohol and drug use is common in the U.S. workplace, relatively little is known about the characteristics of workplaces that test and about the consequences to persons tested. This paper describes the link between drug and alcohol testing and the minority composition of worksites. The data come from a 1999 survey of 264 union officials in the

Gilbert C. Gee; Barbara Curbow; Margaret E. Ensminger; Joan Griffin; David J. Laflamme; Karen McDonnell; David LeGrande; Jacqueline Agnew

2005-01-01

106

[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

107

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

PubMed

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

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

2006-01-01

108

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

PubMed Central

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

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

2008-01-01

109

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

PubMed Central

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

2014-01-01

110

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

Microsoft Academic Search

The purpose of this study was twofold. First, pretreatment correlations are presented among impulsivity, intoxicant use, HIV risk behavior, spirituality, and motivation in a sample of 38 HIV-positive drug users. Second, treatment outcomes are presented from a preliminary study of spiritual self-schema (3-S(+)) therapy - a manual-guided psychotherapy integrating cognitive and Buddhist psychologies - for increasing motivation for abstinence, HIV

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

2007-01-01

111

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

PubMed

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

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

2014-01-01

112

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

113

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

114

ADULT DRUG COURTS Studies Show Courts Reduce Recidivism, but DOJ Could Enhance Future Performance Measure Revision Efforts Why GAO Did This Study  

E-print Network

A drug court is a specialized court that targets criminal offenders who have drug addiction and dependency problems. These programs provide offenders with intensive court supervision, mandatory drug testing, substance-abuse treatment, and other social services as an alternative to adjudication or incarceration. As of June 2010, there were over 2,500 drug courts operating nationwide, of which about 1,400 target adult offenders. The

unknown authors

2011-01-01

115

Genotype and growing environment interaction shows a positive correlation between substrates of raffinose family oligosaccharides (RFO) biosynthesis and their accumulation in chickpea ( Cicer arietinum L.) seeds.  

PubMed

To develop genetic improvement strategies to modulate raffinose family oligosaccharides (RFO) concentration in chickpea ( Cicer arietinum L.) seeds, RFO and their precursor concentrations were analyzed in 171 chickpea genotypes from diverse geographical origins. The genotypes were grown in replicated trials over two years in the field (Patancheru, India) and in the greenhouse (Saskatoon, Canada). Analysis of variance revealed a significant impact of genotype, environment, and their interaction on RFO concentration in chickpea seeds. Total RFO concentration ranged from 1.58 to 5.31 mmol/100 g and from 2.11 to 5.83 mmol/100 g in desi and kabuli genotypes, respectively. Sucrose (0.60-3.59 g/100 g) and stachyose (0.18-2.38 g/100 g) were distinguished as the major soluble sugar and RFO, respectively. Correlation analysis revealed a significant positive correlation between substrate and product concentration in RFO biosynthesis. In chickpea seeds, raffinose, stachyose, and verbascose showed a moderate broad sense heritability (0.25-0.56), suggesting the use of a multilocation trials based approach in chickpea seed quality improvement programs. PMID:23621405

Gangola, Manu P; Khedikar, Yogendra P; Gaur, Pooran M; Bĺga, Monica; Chibbar, Ravindra N

2013-05-22

116

The Yeast Hrs1 Gene Is Involved in Positive and Negative Regulation of Transcription and Shows Genetic Characteristics Similar to Sin4 and Gal11  

PubMed Central

We provide genetic evidence that HRS1/PGD1, a yeast gene previously identified as a suppressor of the hyper-recombination phenotype of hpr1, has positive and negative roles in transcriptional regulation. We have analyzed three differently regulated promoters, GAL1, PHO5 and HSP26, by ?-galactosidase assays of lacZ-fused promoters and by Northern analysis of the endogenous genes. Transcription of these promoters was derepressed in hrs1? mutants under conditions in which it is normally repressed in wild type. Under induced conditions it was either strongly reduced or significantly enhanced depending on the promoter system analyzed. Constitutive transcription was not affected, as determined in ADH1 and TEF2. In addition, Hrs1p was required for mating-factor expression, telomere-linked DNA silencing and DNA supercoiling of plasmids. Furthermore, hrs1? suppressed Ty-insertion mutations and conferred a Gal(-) phenotype. Many of these phenotypes also result from mutations in GAL11, SIN4 or RGR1, which encode proteins of the RNA polII mediator. We also show that gal11? and sin4? partially suppress the hyper-rec phenotype of hpr1 mutants, although to a lesser extent than hrs1?. Our results provide new evidence for the connection between hpr1?-induced deletions and transcription. We discuss the possibility that Hrs1p might be a component of the RNA polII transcription machinery. PMID:9409823

Piruat, J. I.; Chavez, S.; Aguilera, A.

1997-01-01

117

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

118

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

119

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

120

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

Code of Federal Regulations, 2010 CFR

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

2010-01-01

121

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

Code of Federal Regulations, 2013 CFR

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

2013-01-01

122

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

Code of Federal Regulations, 2011 CFR

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

2011-01-01

123

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

Code of Federal Regulations, 2012 CFR

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

2012-01-01

124

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

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

2014-01-01

125

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.Emilia; Salzburger, Walter

2011-01-01

126

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

Microsoft Academic Search

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

Lamei Chen; Alla Perlina; Christopher J. Lee

2004-01-01

127

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

PubMed Central

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

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

2014-01-01

128

False-positive results for ketone with the drug mesna and other free-sulfhydryl compounds.  

PubMed

All free-sulfhydryl compounds tested produced false-positive reactions in the Legal test for ketones. The color developed in the ketone pad of urine dipsticks [N-Multistix SG, Multistix 10 SG (Ames), and Chemstrip 9 (Boehringer-Mannheim)] was misinterpreted for ketone bodies, both by visual and automated reading. In contrast to the reaction with true ketones, a drop of glacial acetic acid added onto the ketone pad of dipsticks discharged the false-positive red color. A red-violet also developed instantly with free -SH compounds in the Acetest tablet assay (Ames), but quickly faded. In general, the presence of acidic groups such as -COOH and -SO3H in the structure appeared to increase the nitroprusside reactivity of free -SH compounds, whereas the presence of a -NH2 group appeared to decrease it. Currently, false-positive ketone reactions ascribable to a free -SH group are most likely to be seen for urine containing mesna. The false-positive test for ketones caused by free -SH compounds can be recognized and ruled out by proper procedures. On the other hand, this chromogenic reaction with free thiols might be used for monitoring urinary excretion of mesna. PMID:3100102

Csako, G

1987-02-01

129

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

E-print Network

and bactericidal activities against the important human pathogen methicillin-resis- tant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis (VRE), and two Gram-negative bacterial species. At least 20 in the preeminent Gram-positive bacterial pathogen Staphylococcus aureus, which is increasingly unresponsive

Nizet, Victor

130

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

131

Recurrent Gastrointestinal Hemorrhage in Treatment with Dasatinib in a Patient Showing SMAD4 Mutation with Acute Lymphoblastic Leukemia Philadelphia Positive and Juvenile Polyposis Hereditary Hemorrhagic Telangiectasia Syndrome.  

PubMed

We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia. PMID:23888243

Sartor, Chiara; Papayannidis, Cristina; Chiara Abbenante, Maria; Iacobucci, Ilaria; Broccoli, Alessandro; Venturi, Claudia; Testoni, Nicoletta; Ferrari, Anna; Martinelli, Giovanni

2013-06-28

132

Recurrent Gastrointestinal Hemorrhage in Treatment with Dasatinib in a Patient Showing SMAD4 Mutation with Acute Lymphoblastic Leukemia Philadelphia Positive and Juvenile Polyposis Hereditary Hemorrhagic Telangiectasia Syndrome  

PubMed Central

We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia. PMID:23888243

Sartor, Chiara; Papayannidis, Cristina; Chiara Abbenante, Maria; Iacobucci, Ilaria; Broccoli, Alessandro; Venturi, Claudia; Testoni, Nicoletta; Ferrari, Anna; Martinelli, Giovanni

2013-01-01

133

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

134

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

135

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

NASA Astrophysics Data System (ADS)

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

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

136

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

PubMed Central

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

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

2013-01-01

137

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

PubMed Central

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

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

2011-01-01

138

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

Microsoft Academic Search

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

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

1995-01-01

139

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

140

"The Show"  

ERIC Educational Resources Information Center

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

Gehring, John

2004-01-01

141

Drugs  

Microsoft Academic Search

Reviews 11 studies, published from the year 1917 to 1910, by Miles, Fiske, Graham, Rowe, Anderson, Marks, Stanley, Johnson, Macht, Isaacs, Greenberg and Lashley on the effects of alcohol, tobacco smoking, drug addiction, addiction to medicines like aspirin, and strychnine and caffeine.

A. T. Poffenberger

1919-01-01

142

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

NASA Astrophysics Data System (ADS)

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

Ikuzawa, Masayuki; Akiduki, Saori; Asashima, Makoto

143

Pollen-specific, but not sperm-specific, genes show stronger purifying selection and higher rates of positive selection than sporophytic genes in Capsella grandiflora.  

PubMed

Selection on the gametophyte can be a major force shaping plant genomes as 7-11% of genes are expressed only in that phase and 60% of genes are expressed in both the gametophytic and sporophytic phases. The efficacy of selection on gametophytic tissues is likely to be influenced by sexual selection acting on male and female functions of hermaphroditic plants. Moreover, the haploid nature of the gametophytic phase allows selection to be efficient in removing recessive deleterious mutations and fixing recessive beneficial mutations. To assess the importance of gametophytic selection, we compared the strength of purifying selection and extent of positive selection on gametophyte- and sporophyte-specific genes in the highly outcrossing plant Capsella grandiflora. We found that pollen-exclusive genes had a larger fraction of sites under strong purifying selection, a greater proportion of adaptive substitutions, and faster protein evolution compared with seedling-exclusive genes. In contrast, sperm cell-exclusive genes had a smaller fraction of sites under strong purifying selection, a lower proportion of adaptive substitutions, and slower protein evolution compared with seedling-exclusive genes. Observations of strong selection acting on pollen-expressed genes are likely explained by sexual selection resulting from pollen competition aided by the haploid nature of that tissue. The relaxation of selection in sperm might be due to the reduced influence of intrasexual competition, but reduced gene expression may also be playing an important role. PMID:23997108

Arunkumar, Ramesh; Josephs, Emily B; Williamson, Robert J; Wright, Stephen I

2013-11-01

144

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

PubMed

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

Jones, Alan Wayne; Holmgren, Anita

2013-03-01

145

Sci Show  

NSDL National Science Digital Library

The Sci Show, an entertaining series of quirky YouTube videos, tackles topics ranging from âÂÂHow Do Polarized Sunglasses Workâ to âÂÂStrong Interaction: The Four Fundamental Forces of Physics.â Most episodes are less than five minutes long, but they pack a wallop of handy science info. Anyone short on time but long on big questions will benefit from the series. Episodes will be helpful to teachers and parents looking to spark enthusiasm in young minds. Viewers may want to start with recent episodes like âÂÂTodayâÂÂs Mass Extinction,â and the âÂÂWorldâÂÂs First See-Through Animalâ and âÂÂHow Do Animals Change Color?â before digging into the archives for gems like âÂÂThe Truth About Gingersâ and âÂÂThe Science of Lying.âÂÂ

146

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

PubMed Central

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

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

2013-01-01

147

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

NASA Astrophysics Data System (ADS)

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

Zhang, Lijuan; Li, Yuhao; Zhou, Yunshan

2010-04-01

148

A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs.  

PubMed

Dengue fever is an emerging arboviral disease for which no vaccine or antiviral treatment exists and that causes thousands of fatalities each year. To develop an in vivo test system for antidengue drugs, AG129 mice, which are deficient for the interferon- alpha / beta and - gamma receptors, were injected with unadapted dengue virus, resulting in a dose-dependent transient viremia lasting several days and peaking on day 3 after infection. Additionally, nonstructural protein 1, increased levels of proinflammatory cytokines, and neutralizing IgM and IgG antibodies were found, and mice had splenomegaly. Oral administration of the antiviral compounds 7-deaza-2'-C-methyl-adenosine, N-nonyl-deoxynojirimycin, or 6-O-butanoyl castanospermine significantly reduced viremia in a dose-dependent manner, even after delayed treatment, leading to a reduction of splenomegaly and proinflammatory cytokine levels. The results validate this dengue viremia mouse model as a suitable system for testing antidengue drugs and indicate that antiviral treatment during the acute phase of dengue fever can reduce the severity of the disease. PMID:17262707

Schul, Wouter; Liu, Wei; Xu, Hao-Ying; Flamand, Marie; Vasudevan, Subhash G

2007-03-01

149

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

150

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

151

Drugs education the American way  

Microsoft Academic Search

Provides an account of some of the author’s observations while on a Winston Churchill Travelling Fellowship to the USA to study drugs education. Shows some of the ways drugs education is made memorable in US schools, and how positive alternatives to drink, tobacco and drugs are promoted in California. Concludes that schools and other agencies within an education authority could

Allison Kesterton

1997-01-01

152

Injecting drug use is associated with a more rapid CD4 cell decline among treatment na?ve 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) naďve 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 naďve 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 naďve 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

153

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

PubMed

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 the treatment of pain. The epidemiology of prescription opioid use and abuse is reviewed. Non-medical use and abuse of prescription opioids are on the rise in the United States, illicit use of several widely prescribed opioids has increased disproportionately more than illicit use, and the prevalence of prescription opioid abuse appears to be similar to that of heroin and cocaine abuse. There is a paucity of abuse liability testing of prescription opioids, and methods should be developed to fill critical gaps in our knowledge in this area. The role of regulatory agencies in preventing diversion of prescription opioids and identifying potential sources of diversion are discussed. More research is needed to identify those populations most at risk for abusing prescription opioids, and then to develop appropriately targeted prevention programs. Treatment options are discussed; these depend on whether or not an abuser is in pain. Prescription opioid abuse has harmful ramifications for the legitimate and appropriate use of opioids, including stigmatization, opiophobia, and undertreatment of pain. Recommended steps to take include further epidemiological research, laboratory testing of prescription opioids to determine abuse liability, and clinical trials to determine the efficacy of different approaches to the prevention and treatment of prescription opioid abuse. PMID:12633908

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

2003-04-01

154

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

E-print Network

tx H2O | pg. 2 Dr. Chu testing chemicals. Photo by Leslie Jordan. Illustration by Mary-Margaret Shread. tx H2O | pg. 3 Story by Leslie Jordan Scientists? expanding research and technologies show that traces of pharmaceuticals in water may... obscurity to controversy After a decade of researching pharmaceuticals and personal care products (PPCPs) in water and treated wastewater, Dr. Bryan Brooks, professor of environmental science and biomedical studies at Baylor University, has seen...

Jordan, Leslie

2010-01-01

155

Differences in treatment outcome between male alcohol dependent offenders of domestic violence with and without positive drug screens  

Microsoft Academic Search

Men who are violent toward their partners tend to have a dual problem with alcohol and drug use, yet little is known about differences between men with single rather than dual problems. This study was one of the first to evaluate differences between alcohol dependent men who were arrested for Intimate Partner Violence (IPV) with and without concurrent illicit drug

Caroline J. Easton; Dolores Mandel; Theresa Babuscio; Bruce J. Rounsaville; Kathleen M. Carroll

2007-01-01

156

Illicit drug use, depression and their association with highly active antiretroviral therapy in HIV-positive women  

Microsoft Academic Search

BackgroundWe examined the interaction of illicit drug use and depressive symptoms, and how they affect the subsequent likelihood of highly active antiretroviral therapy (HAART) use among women with HIV\\/AIDS.

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

2007-01-01

157

Interactive ``Video Doctor'' Counseling Reduces Drug and Sexual Risk Behaviors among HIV-Positive Patients in Diverse Outpatient Settings  

Microsoft Academic Search

BackgroundReducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission. Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks, it is unknown how to best provide “prevention with positives” in clinical settings. Positive Choice, an interactive, patient-tailored computer program, was developed in the

Paul Gilbert; Daniel Ciccarone; Stuart A. Gansky; David R. Bangsberg; Kathleen Clanon; Stephen J. McPhee; Sophia H. Calderón; Alyssa Bogetz; Barbara Gerbert; Landon Myer

2008-01-01

158

Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells  

PubMed Central

Background Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-?-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. Results We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-?-cyclodextrin (CM-?-CD) nanoparticles (FA-BSA-CM-?-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of ?18.6 mV. FA-BSA-CM-?-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-?-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs. Conclusions These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-?-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors. PMID:25358257

2014-01-01

159

Hero or Hypocrite?United States and International Media Portrayals of Carl Lewis Amid Revelations of a Positive Drug Test  

Microsoft Academic Search

This article examines press coverage of track and field athlete Carl Lewis amid reports in April 2003 that he tested positive for three banned stimulants prior to United States Olympic Trials in 1988. Lewis, of course, won the 1988 100-meter gold medal after Canadian Ben Johnson tested positive for anabolic steroids, a development that brought disgrace to Johnson and adulation

Bryan E. Denham

2004-01-01

160

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

161

Perceptions of community- and family-level injection drug user (IDU)- and HIV-related stigma, disclosure decisions and experiences with layered stigma among HIV-positive IDUs in Vietnam  

Microsoft Academic Search

This paper explores how perceived stigma and layered stigma related to injection drug use and being HIV-positive influence the decision to disclose one's HIV status to family and community and experiences with stigma following disclosure among a population of HIV-positive male injection drug users (IDUs) in Thai Nguyen, Vietnam. In qualitative interviews conducted between 2007 and 2008, 25 HIV-positive male

A. E. Rudolph; W. W. Davis; V. M. Quan; T. V. Ha; N. L. Minh; A. Gregowski; M. Salter; D. D. Celentano; V. Go

2011-01-01

162

Perceptions of community- and family-level injection drug user (IDU)- and HIV-related stigma, disclosure decisions and experiences with layered stigma among HIV-positive IDUs in Vietnam  

Microsoft Academic Search

This paper explores how perceived stigma and layered stigma related to injection drug use and being HIV-positive influence the decision to disclose one's HIV status to family and community and experiences with stigma following disclosure among a population of HIV-positive male injection drug users (IDUs) in Thai Nguyen, Vietnam. In qualitative interviews conducted between 2007 and 2008, 25 HIV-positive male

A. E. Rudolph; W. W. Davis; V. M. Quan; T. V. Ha; N. L. Minh; A. Gregowski; M. Salter; D. D. Celentano; V. Go

2012-01-01

163

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

164

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

PubMed Central

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

165

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

PubMed Central

Introduction Achievement of optimal medication adherence and management of antiretroviral toxicity pose great challenges among Ethiopian patients with HIV/AIDS. There is currently a lack of long-term follow-up studies that identify the barriers to, and facilitators of, adherence to antiretroviral therapy (ART) in the Ethiopian setting. Therefore, we aim to investigate the level of adherence to ART and a wide range of potential influencing factors, including adverse drug reactions occurring with ART. Methods and analysis We are conducting a 1-year prospective cohort study involving adult patients with HIV/AIDS starting on ART between December 2012 and March 2013. Data are being collected on patients’ appointment dates in the ART clinics. Adherence to ART is being measured using pill count, medication possession ratio and patient's self-report. The primary outcome of the study will be the proportion of patients who are adherent to their ART regimen at 3, 6 and 12?months using pill count. Taking 95% or more of the dispensed ART regimen using pill count at given points of time will be considered the optimal level of adherence in this study. Data will be analysed using descriptive and inferential statistical procedures. Ethics and dissemination Ethics approval was obtained from the Tasmania Health and Medical Human Research Ethics Committee and Bahir-Dar University's Ethics Committee. The results of the study will be reported in peer-reviewed scientific journals, conferences and seminar presentations. PMID:24176794

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

2013-01-01

166

Crystal structure of peptidyl-tRNA hydrolase from a Gram-positive bacterium, Streptococcus pyogenes at 2.19 ? 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 Ĺ 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 Ĺ, 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

167

Granulocyte colony-stimulating factor-producing undifferentiated carcinoma of the colon mimicking a pulmonary giant cell carcinoma: a case showing overexpression of CD44 along with highly proliferating nestin-positive tumor vessels  

PubMed Central

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are known for their aggressive behavior. Only four cases of G-CSF-producing colorectal carcinoma have been previously reported. Herein, we present a case of an undifferentiated carcinoma of the descending colon showing G-CSF production and giant cell carcinoma morphology in a 93-year-old woman. A tumor with a diameter of 80 mm was identified in the descending colon via computed tomography. Descending colectomy was performed involving the abdominal wall where tumor invasion was observed. The white blood cell count, which was elevated before resection, decreased to normal levels after intervention. However, local recurrence at the resected site was detected 39 days after surgery. Upon recurrence, increased white blood cell counts and serum G-CSF were seen. The patient died because of respiratory failure 98 days after colectomy. By using immunohistochemistry, G-CSF expression was detected in tumor cells in the resected specimen, along with overexpression of CD44 and highly proliferating nestin-positive tumor vessels. The poor clinical outcome of this patient is consistent with previous reports that the expression of these three molecules predict poor prognosis. While G-CSF can be a therapeutic target considering its auto/paracrine function to induce tumor growth via the G-CSF receptor, CD44 and nestin may also be possible candidate therapeutic targets. Further studies are required to assess the efficacy of treatments targeting these three molecules.

Tajima, Shogo; Waki, Michihiko; Tsuchiya, Tomonori; Hoshi, Shoji

2014-01-01

168

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

PubMed

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

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

2014-09-01

169

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

PubMed Central

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

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

2013-01-01

170

Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal.  

PubMed

Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-h prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for 1 or 3 weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior ("retreats") regarding goal-box entry, reflecting cocaine's dual positive+negative effects. Once established, retreat behaviors persisted over the course of 1 or 3 weeks days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli. PMID:22005601

Su, Zu-In; Kichaev, Gleb; Wenzel, Jennifer; Ben-Shahar, Osnat; Ettenberg, Aaron

2012-01-01

171

Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal  

PubMed Central

Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-hr prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for one or three weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior (“retreats”) regarding goal-box entry, reflecting cocaine’s dual positive + negative effects. Once established, retreat behaviors persisted over the course of 6 and 20 days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli. PMID:22005601

Su, Zu-In; Kichaev, Gleb; Wenzel, Jennifer; Ben-Shahar, Osnat; Ettenberg, Aaron

2011-01-01

172

The Influence of Psychological Variables on Health Related Quality of Life among HIV Positive Individuals with a History of Intravenous Drug Use  

PubMed Central

Objective Intravenous drug use (IDU) remains a prominent pathway of HIV transmission in the United States, though little is know about modifiable factors influencing quality of life among IDUs. The goal of this study was to evaluate the influence of psychological variables (e.g., depression and anxiety) on health related quality of life among HIV-positive individuals with a history of IDU who were enrolled in outpatient treatment for opioid dependence. Method 108 HIV-positive individuals with a history of IDU and participating in current outpatient treatment for opiate dependence who were screened for participation in a depression and adherence study reported sociodemographic data, depressive and anxiety symptoms and health-related quality of life (HRQoL; Multidimensional Health Assessment using the ACTG-SF 21). Results Multiple regression models controlling for disease stage and background characteristics identified significant negative relationships between General Health Perception and Functioning without Pain for anxiety and depression, and between Role Functioning and Physical Functioning for anxiety. CD4 cell count was significantly related to Physical Functioning only. Conclusions Results indicate that distress (both depression and anxiety) contribute significantly to variation in HRQoL over and above the effects of disease variables. Effective depression and anxiety treatment may result in improved overall functioning. PMID:24377169

Psaros, Christina; O'Cleirigh, Conall; Bullis, Jacqueline R.; Markowitz, Sarah M.; Safren, Steven A.

2013-01-01

173

drug discovery drug discovery  

E-print Network

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

174

Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: the SHR strain.  

PubMed

Studies have suggested that the endocannabinoid system is implicated in the pathophysiology of schizophrenia. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs display hyperlocomotion - reverted by atypical and typical antipsychotics. These results suggest that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia and the effects of potential drugs with an antipsychotic profile. The aim of this study was to investigate the effects of WIN55-212,2 (CB1/CB2 agonist), ACEA (CB1 agonist), rimonabant (CB1 inverse agonist), AM404 (anandamide uptake/metabolism inhibitor), capsaicin (agonist TRPV1) and capsazepine (antagonist TRPV1) on the social interaction and locomotion of control animals (Wistar rats) and SHRs. The treatment with rimonabant was not able to alter either the social interaction or the locomotion presented by Wistar rats (WR) and SHR at any dose tested. The treatment with WIN55-212,2 decreased locomotion (1mg/kg) and social interaction (0.1 and 0.3mg/kg) of WR, while the dose of 1mg/kg increased social interaction of SHR. The treatment with ACEA increased (0.3mg/kg) and decreased (1mg/kg) locomotion of both strain. The administration of AM404 increased social interaction and decreased locomotion of SHR (5mg/kg), and decreased social interaction and increased locomotion in WR (1mg/kg). The treatment with capsaicin (2.5mg/kg) increased social interaction of both strain and decreased locomotion of SHR (2.5mg/kg) and WR (0.5mg/kg and 2.5mg/kg). In addition, capsazepine (5mg/kg) decreased locomotion of both strains and increased (5mg/kg) and decreased (10mg/kg) social interaction of WR. Our results indicate that the schizophrenia-like behaviors displayed by SHR are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment of schizophrenia. PMID:24556469

Almeida, Valéria; Peres, Fernanda F; Levin, Raquel; Suiama, Mayra A; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

2014-03-01

175

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

176

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

PubMed Central

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

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

2014-01-01

177

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

178

Towards estimation of HIV-1 date of infection: a time-continuous IgG-model shows that seroconversion does not occur at the midpoint between negative and positive tests.  

PubMed

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

Skar, Helena; Albert, Jan; Leitner, Thomas

2013-01-01

179

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

PubMed Central

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

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

2014-01-01

180

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

181

The Art Show  

ERIC Educational Resources Information Center

This article describes what once was thought to be impossible--a formal art show extravaganza at an elementary school with 1,000 students, a Department of Defense Dependent School (DODDS) located overseas, on RAF Lakenheath, England. The dream of this this event involved the transformation of the school cafeteria into an elegant art show

Scolarici, Alicia

2004-01-01

182

Exceptional Leadership: Allow Positive Psychology to Show you the Way  

Microsoft Academic Search

The recent events of the Atlanta Falcon's star quarterback Michael Vick are a strong reminder of just how essential character is to leadership. Vick is allegedly guilty of promoting\\/sponsoring dog fighting, along with general cruelty to animals. He has been indicted by the federal government. Anyone who knows football would not question Vick's talent as a quarterback. Some consider him

Johnny Parker

183

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.

184

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

185

Sexual Risk Taking and Club Drug Use Across Three Age Cohorts of HIV-positive Gay and Bisexual Men in New York City  

PubMed Central

This study examined club drug use, (i.e., cocaine, ecstasy, ketamine, 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 to 61, and considered these behaviors in relation to age category (20s, 30s, 40+) and number of years living with HIV. Club drug use was common across all age categories, with differences arising only in the type of club drug used. Multivariate logistic regression modeling indicated older participants (30s, 40+) were more likely to use cocaine and methamphetamine and less likely to use GHB and ketamine than those in their 20s. We examined unprotected anal intercourse (UAI) with casual partners in relation to age category, the number of years living with HIV, and club drug use. The likelihood of engaging in UAI with seronegative casual partners was greater among those in their 20s than those in their 30's or 40+. Further, participants were equally likely to engage in unprotected receptive anal intercourse and unprotected insertive anal intercourse with each casual partner serostatus type. With regard to number of years living with HIV, those living longer with the disease were more likely to report UAI with casual partners with a seropositive status than with a negative or unknown serostatus. Our findings suggest that UAI and club drug use is common among seropositive gay and bisexual men regardless of age category, but that differential patterns of risk emerge in relation to the number of years one has been living with HIV and age. These findings are of significance as both the aging population of seropositive gay and bisexual men and HIV infection rates continue to grow, and demonstrate a need for differentiated and tailored prevention strategies across the age continuum. PMID:22022849

Pappas, Molly K.; Halkitis, Perry N.

2011-01-01

186

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

187

Showing What They Know  

ERIC Educational Resources Information Center

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

Cech, Scott J.

2008-01-01

188

Chemistry Game Shows  

Microsoft Academic Search

We present a technological improvement to the use of game shows to help students review for tests. Our approach uses HTML files interpreted with a browser on a computer attached to an LCD projector. The HTML files can be easily modified for use of the game in a variety of courses.

Susan Campbell; Jennifer Muzyka

2002-01-01

189

Obesity in show cats.  

PubMed

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

Corbee, R J

2014-12-01

190

Is Sexual Serosorting Occurring Among HIV-Positive Injection Drug Users? Comparison Between Those with HIV-Positive Partners Only, HIV-Negative Partners Only, and Those with any Partners of Unknown Status  

Microsoft Academic Search

Using baseline data from a multi-site, randomized controlled study (INSPIRE), we categorized 999 HIV-positive IDUs into three\\u000a groups based on serostatus of their sex partners. Our data provide some evidence for serosorting occurring in our sample;\\u000a about 40% of the sample had sex exclusively with HIV-positive partners, and about half of them reported having unprotected\\u000a sex with these partners. Twenty

Yuko Mizuno; David W. Purcell; Mary H. Latka; Lisa R. Metsch; Helen Ding; Cynthia A. Gomez; Amy R. Knowlton

2010-01-01

191

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

192

Drug interactions with antiviral drugs.  

PubMed

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

Taburet, A M; Singlas, E

1996-05-01

193

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

PubMed

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

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

2014-11-01

194

Show-Me Center  

NSDL National Science Digital Library

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

195

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

196

The Truman Show  

Microsoft Academic Search

The Truman Show is hardly a film you would automatically speak about as a game. At first glance, it is tempting to interpret the story of\\u000a Truman Burbank — his perpetual subjection to the artificial (televisual) world of Seahaven and its gargantuan reality TV project,\\u000a his eventual escape from the “OmniCam Ecosphere” building and the paternalistic surveillance of director Christof

Rolf F. Nohr

197

The Graphing Game Show  

NSDL National Science Digital Library

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

2011-01-01

198

Obesity in show dogs.  

PubMed

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

Corbee, R J

2012-08-11

199

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.

200

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 W.

201

Not a "reality" show.  

PubMed

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

Wrong, Terence; Baumgart, Erica

2013-01-01

202

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

203

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

204

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

205

"Show me" bioethics and politics.  

PubMed

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

Christopher, Myra J

2007-10-01

206

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

207

Mirazid shows insignificant activity against ovine fascioliasis.  

PubMed

In a recent study, the fasciolicidal activity of Mirazid (a myrrh-derived drug) and its effect on the function and histopathology of host liver were investigated in Egyptian sheep, with triclabendazole (TCBZ) used as the positive control. Sheep were infected with metacercariae (150/animal) and treated 3 months later, either with Mirazid (10 mg/kg/day for six consecutive days) or TCBZ (a single dose of 10 mg/kg), or left untreated, as controls. When the animals were killed 4 weeks after the end of treatment, no Fasciola flukes or eggs could be found in the animals given TCBZ but the number of flukes found in the Mirazid-treated animals was only 6% lower than that recorded in the untreated sheep (a statistically insignificant difference). In terms of their Fasciola egg loads, serum concentrations of hepatic enzymes and hepatic histopathological changes, the Mirazid-treated sheep appeared very similar to the untreated, infected animals. The TCBZ-treated animals, in contrast, showed remarkably little evidence of hepatic pathology. It therefore appears that, in the treatment of ovine fascioliasis, at least some batches of Mirazid have little, if any, value. PMID:19825282

Botros, S S; El-Lakkany, N M; Badawy, A A; Mahmoud, S S; Ebeid, F A; Fenwick, A

2009-10-01

208

Position of chromatographic techniques in screening for detection of drugs or poisons in clinical and forensic toxicology and/or doping control.  

PubMed

This paper reviews chromatographic screening procedures for simultaneous detection of several drug classes relevant to clinical and forensic toxicology or doping control in urine or blood using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with a diode-array detector (LC-DAD) or a mass spectrometer (LC-MS). The pros and cons of the different techniques and procedures are discussed leading to the following conclusions and perspectives. GC-MS, especially in the electron ionization full-scan mode, is still the method of choice for comprehensive screening providing best separation power, specificity and universality, although requiring derivatization. LC-DAD is also often used for screening, but its separation power and its specificity are still inferior to those of GC-MS. Finally, LC-MS has shown to be an ideal supplement, especially for the detection of more polar, thermolabile and/or low-dose drugs, especially in blood plasma. It may become the gold standard in clinical and forensic toxicology and doping control if, at a later date, the costs of the apparatus will be markedly reduced, the current disadvantages like irreproducibility of fragmentation, reduction of ionization by matrix, etc. will be overcome, and finally if one of the increasing number of quite different techniques will become the apparatus standard. PMID:15576292

Maurer, Hans H

2004-01-01

209

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

210

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

PubMed

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

Mousavi, Fariba; Garcia, Danilo; Jimmefors, Alexander; Archer, Trevor; Ewalds-Kvist, Béatrice

2014-01-01

211

UCSF Cancer Center Research Shows Promise of New Drugs  

Cancer.gov

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

212

Positive Lives  

NSDL National Science Digital Library

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

213

Position Information Position Details  

E-print Network

policies, admission policies, scholarship and loan programs, athletics, and other school_10398 Department College of Education - Masters in Teaching Program Pay Band Faculty FLSA Status Exempt The College of Education invites applications for a 1-year, full time non-tenure track Instructor position w

Carter, John

214

Coinfection with hepatitis C virus (HCV), oxidative stress and antioxidant status in HIV-positive drug users in Miami1,2  

PubMed Central

Background The pathogenesis of HIV/HCV-coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV-coinfected and HIV-monoinfected adults. Methods Demographics, medical history, and proof of HIV, hepatitis A, B and C were obtained. HIV-viral load, CD4-count, CBC, chemistries, plasma zinc, selenium, vitamins A and E were determined. Malondialdehyde (MDA) and glutathione-peroxidase were obtained as measures of oxidative stress. APRI and FIB-4 markers were calculated. Results Significant differences were found between HIV/HCV-coinfected and HIV-monoinfected participants in levels of ALT (51.4±50.6 vs. 31.9±43.1U/L, p=0.014), AST (56.2±40.9 vs. 34.4±30.2U/L; p<0.001), APRI (0.52±0.37 vs. 0.255±0.145, p=0.0001), FIB-4 (1.64±.0.91 vs. 1.03±0.11, p=0.0015) and plasma albumin (3.74±0.65 vs. 3.94±0.52g/dL, p=0.038). There were no significant differences in CD4-count, HIV-viral load or ART between groups. Mean MDA was significantly higher (1.897±0.835 vs. 1.344±0.223nmol/mL, p=0.006), and plasma antioxidants were lower, (vitamin A [39.5±14.1 vs. 52.4±16.2µg/dL, p=0.0004], vitamin E [8.29±2.1 vs. 9.89±4.5µg/mL, p=0.043] and zinc [0.61±0.14 vs. 0.67±0.15mg/L, p=0.016]) in the HIV/HCV-coinfected compared to the HIV-monoinfected participants, which remained significant after adjusting for age, gender, CD4-count, HIV-viral load, injection drug-use and race. There were no significant differences in glutathione-peroxidase, selenium, BMI, and alcohol, and tobacco between groups. Glutathione-peroxidase significantly increased as liver disease advanced, as measured by APRI (?= 0.00118, p=0.0082) and FIB-4 (?=0.0029, p=0.0177). Vitamin A significantly decreased (?=?0.00581, p=0.0417) as APRI increased. Conclusion HIV/HCV-coinfection is associated with increased oxidative stress and decreased plasma antioxidants when compared to HIV-monoinfection. Research is needed to determine whether antioxidant supplementation delays liver disease in HIV/HCV-coinfection. PMID:20500231

Baum, MK; Sales, S; Jayaweera, DT; Lai, S; Bradwin, G; Rafie, C; Page, JB; Campa, A

2010-01-01

215

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description.gossinternational.com Machinery Engineering Company Overview: Degree: Paid Fall, Spring, Summer Yes Career & Internship Fair innovation. Chemical Engineering, Computer Engineering, Computer Science, Electrical Engineering, Mechanical

New Hampshire, University of

216

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career and Internship Fair March 5, 2013 & Clinical Practice. Business Administration, Chemistry, Computer Engineering, Computer Science, Health

Pringle, James "Jamie"

217

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career & Internship Fair October 22, 2013 Engineering, Computer Engineering, Computer Science, Mechanical Engineering Yes Entry Level

New Hampshire, University of

218

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career & Internship Fair October 22, 2013, "Where did I leave my electrosurgical unit?" Computer Engineering, Computer Science, Electrical

New Hampshire, University of

219

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career & Internship Fair October 22, 2013. Business Administration, Computer Engineering, Computer Science, Liberal Arts Majors No Entry Level

New Hampshire, University of

220

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career & Internship Fair October 22, 2013 at Riverbed. Computer Engineering, Computer Science, Electrical Engineering Yes Entry Level

New Hampshire, University of

221

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 Engineer (aerospace), .Net Developer, and Data Architect. Computer Engineering, Computer Science

New Hampshire, University of

222

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career & Internship Fair October 22, 2013 sensor network products. Computer Engineering, Computer Science, Electrical Engineering Yes Entry Level

New Hampshire, University of

223

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 efficient process. Business Administration, Civil Engineering, Computer Engineering, Computer Science

New Hampshire, University of

224

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013. Computer Engineering, Computer Science, Electrical Engineering, Math & Statistics, Physics Yes Entry Level

New Hampshire, University of

225

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013) software by leading industry analysts. Computer Engineering, Computer Science Yes Entry Level

New Hampshire, University of

226

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description meetings. tylertech.com Technology Company Overview: Degree: Paid Summer Yes Career & Internship Fair Specialist Business Administration, Computer Engineering, Computer Science, Electrical Engineering, Math

New Hampshire, University of

227

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 customer requirements. Business Administration, Computer Engineering, Computer Science, Economics, Liberal

New Hampshire, University of

228

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 Administration, Computer Engineering, Computer Science, Health & Human Services, Hospitality, Liberal Arts Majors

New Hampshire, University of

229

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

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Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 employer. Business Administration, Computer Science Yes Entry LevelInternships Summer internships

New Hampshire, University of

230

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 in its class. Business Administration, Computer Science, Economics, Electrical Engineering Yes Entry

New Hampshire, University of

231

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 ...

232

Making drugs accessible.  

PubMed

Making drugs accessible for common HIV-associated illnesses in West Africa is discussed. HIV-positive people in Ouagadougou, Burkina Faso, could not afford drugs for treating their illnesses; thus, volunteers from La Bergerie-FUC, a Christian organization, have established a day care center for HIV-positive people. A French church supplies the drugs; oral rehydration salts are provided through the Ministry of Health. Since the organization did not have enough drugs to meet the needs of all its patients, two strategies were developed to improve its drug supply. The first strategy was to raise money to buy drugs through the support of a local NGO, the Initiative Privee et Communautaire de lutte contre le SIDA (IPC). IPC initially refused to support them, but, eventually agreed to fund drug purchasing as a pilot project. The second strategy was to look at ways of reducing the cost of drugs, which resulted in a list of essential drugs for HIV-associated infections. The list was approved by Care and Support Committee of the national AIDS program for use by other organizations. The organizations have created a national network to improve the delivery of community-based care and support services in Burkina Faso. Recently, the national AIDS program has asked this network to help them change the national essential drugs list to include essential drugs for treating common HIV-associated infections. PMID:12349193

1999-01-01

233

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

PubMed Central

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

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

2012-01-01

234

Proper Use of Sulfonamides in Market Show Animals  

E-print Network

When administering a drug to a show animal, the owner is responsible for ensuring that there will be no drug residues in the animal's urine when it is tested at a show. Sulfonamides are of special concern because, even when they are administered...

Faries Jr., Floron C.; Fajt, Virginia

2008-02-14

235

Drug Design: Designer Drugs  

Microsoft Academic Search

\\u000a This article interrogates the contemporary comprehension of rational drug design in the development of pharmaceutical products\\u000a with therapeutic and enhancing properties and its extensions to designer drugs on the grey and black market. The latter not\\u000a only evidently leads to ethical and hence societal questions of standardizing the state of well-being of body and mind, but\\u000a also virtually sets the

Gerd Folkers; Elvan Kut; Martin Boyer

236

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

PubMed Central

Hepatitis C virus (HCV) is hyperendemic among injection drug users (IDUs). However, few scientifically proven interventions to prevent secondary transmission of HCV from infected IDUs to others exist. This report describes the design, feasibility, and baseline characteristics of participants enrolled in the Study to Reduce Intravenous Exposure (STRIVE). STRIVE was a multisite, randomized-control trial to test a behavioral intervention developed to reduce distribution of used injection equipment (needles, cookers, cottons, and rinse water) and increase health-care utilization among antibody HCV (anti-HCV) positive IDUs. STRIVE enrolled anti-HCV positive IDU in Baltimore, New York City, and Seattle; participants completed behavioral assessments and venipuncture for HIV, HCV-RNA, and liver function tests (LFTs) and were randomized to attend either a six-session, small-group, peer-mentoring intervention workshop or a time-matched, attention-control condition. Follow-up visits were conducted at 3 and 6 months. At baseline, of the 630 HCV-positive IDUs enrolled (mean age of 26 years, 60% white, 76% male), 55% reported distributive needle sharing, whereas 74, 69, and 69% reported sharing cookers, cottons, and rinse water, respectively. Health-care access was low, with 41% reporting an emergency room as their main source of medical care. Among those enrolled, 66% (418/630) were randomized: 53% (222/418) and 47% (196/418) to the intervention and control conditions, respectively. Follow-up rates were 70 and 73% for the 3- and 6-month visits, respectively. As distributive sharing of used injection equipment was common while reports of receiving HCV care were low, these findings indicate an urgent need for HCV-related interventions with IDUs and demonstrate the acceptability and feasibility to do so. PMID:17200799

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

2007-01-01

237

Scaring Kids' Shows Off TV.  

ERIC Educational Resources Information Center

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

Raspberry, William

1980-01-01

238

Midterm Picnic ELI Talent Show  

E-print Network

Highlights Midterm Picnic ELI Talent Show Notes from the Office Birthdays Manners Grammar The will be on the Activities Board and in next week's Weekly. ELI Talent Show Do you have a talent? Show it to us at the ELI Talent Show! The talent show is open to ELI students, faculty, staff, and LAs. Acts can include

Pilyugin, Sergei S.

239

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description products have a 98% Customer Satisfaction rating! Due to growth we have moved our headquarters to a new 180&D, QA, Customer Service, Marketing and Product Management departments are not out-sourced. Our GTAC team

Pringle, James "Jamie"

240

Positive Psychology \\  

Microsoft Academic Search

Positive psychology is the study of human strength, resilience, and optimal human functioning. The goal of positive psychology is to make people happier by understanding and building positive emotion, gratification and meaning. The constructs of happiness, hope, optimism, well-being, resilience and flow are examined in how they relate to positive psychology. The \\

Andrew W Fleming

2006-01-01

241

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 are our top priority, and team members are our greatest asset! Computer Engineering, Computer Science

New Hampshire, University of

242

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description Ecology or Management, Environmental Science, or Veterinary Science. The large number of animals.yorkcenterforwildlife.org Wildlife Rehabilitation Company Overview: Degree: Unpaid Fall, Spring, Summer No Career & Internship Fair

New Hampshire, University of

243

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description of Science Program in Civil Engineering or related engineering fields. Working knowledge of computer Overview: Degree: Paid Fall, Spring, Summer Yes Career & Internship Fair October 22, 2013 -- 12:00-4:00pm

New Hampshire, University of

244

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description Overview: Degree: No Career & Internship Fair October 22, 2013 -- 12:00-4:00pm Yes Software Engineer Permanent Residency or US Citizenship required. Computer Engineering, Computer Science, Electrical

New Hampshire, University of

245

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 and dispatching and asset maintenance. Computer Science Yes Entry LevelInternships Software Engineer (Intern

New Hampshire, University of

246

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description Company Overview: Degree: Yes Career & Internship Fair October 22, 2013 -- 12:00-4:00pm Not at this time, Chemistry, Computer Engineering, Computer Science, Economics, Electrical Engineering, Math & Statistics

New Hampshire, University of

247

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 program. Computer Science Yes Entry LevelInternships Software Intern Whittemore Center Jacobs Technology

New Hampshire, University of

248

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Yes Career & Internship Fair October 22, 2013, and dramatically change the price/performance of data center networks. Computer Engineering, Computer Science

New Hampshire, University of

249

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 in providing innovative products and services to the life science market. Our SaaS based business collaboration

New Hampshire, University of

250

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description/Hardware Company Overview: Degree: No Career & Internship Fair October 22, 2013 -- 12:00-4:00pm Yes Pre of ownership. Computer Engineering, Computer Science No Entry LevelInternships Whittemore Center Oracle

New Hampshire, University of

251

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 submarine technology to a new level. Civil Engineering, Computer Engineering, Computer Science, Electrical

New Hampshire, University of

252

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013 Majors, Thompson School Applied Science No Entry LevelInternships Whittemore Center PC Connection, Inc

New Hampshire, University of

253

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career and Internship Fair March 5, 2013 -- 12 America, Asia and Europe as well as a global sales and support network. Computer Science, Electrical

Pringle, James "Jamie"

254

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: No Career & Internship Fair October 22, 2013, Computer Engineering, Computer Science, Economics, Liberal Arts Majors, Math & Statistics Yes Entry Level

New Hampshire, University of

255

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Unsure Career & Internship Fair October 22, 2013 -- 12:00-4:00pm Yes Sales, Finance, Customer Service, IT, Quality, Lab Science Thermo Fisher Scientific

New Hampshire, University of

256

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description in engineering design process and materials science Strong written and oral communication skills Must be able & Internship Fair October 22, 2013 -- 12:00-4:00pm Yes Engineer Level I Safran is a world-class manufacturer

New Hampshire, University of

257

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

E-print Network

Company: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description: Description: Paid/Unpaid: When: Hire International Students: Unsure Career & Internship Fair October 22, 2013 and on-going marketing program support. Computer Engineering, Computer Science No Entry Level

New Hampshire, University of

258

The drug cocktail network  

PubMed Central

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

2012-01-01

259

Antitumor drugs as photochemotherapeutic agents  

NASA Astrophysics Data System (ADS)

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

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

1991-11-01

260

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.

261

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

262

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

263

Overview of Selected Drug Trends.  

ERIC Educational Resources Information Center

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

Adams, Edgar H.; And Others

264

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 ...

265

Managing Beef Cattle for Show  

E-print Network

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

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

2001-11-16

266

Nursing Positions  

MedlinePLUS

... more deeply with this hold. Continue The Side-Lying Position This position is comfortable for mothers who' ... crib or bassinet before falling asleep. Start by lying on your side with your baby on his ...

267

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.

268

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

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

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

269

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

Federal Register 2010, 2011, 2012, 2013

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

2011-04-01

270

Positional plagiocephaly  

PubMed Central

Cranial asymmetry occurring as a result of forces that deform skull shape in the supine position is known as deformational plagiocephaly. The risk of plagiocephaly may be modified by positioning the baby on alternate days with the head to the right or the left side, and by increasing time spent in the prone position during awake periods. When deformational plagiocephaly is already present, physiotherapy (including positioning equivalent to the preventive positioning, and exercises as needed for torticollis and positional preference) has been shown to be superior to counselling about preventive positioning only. Helmet therapy (moulding therapy) to reduce skull asymmetry has some drawbacks: it is expensive, significantly inconvenient due to the long hours of use per day and associated with skin complications. There is evidence that helmet therapy may increase the initial rate of improvement of asymmetry, but there is no evidence that it improves the final outcome for patients with moderate or severe plagiocephaly. PMID:23024590

Cummings, Carl

2011-01-01

271

Rings in drugs.  

PubMed

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

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

2014-07-24

272

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

273

RISK AVERSION IN GAME SHOWS  

Microsoft Academic Search

We review the use of behavior from television game shows to infer risk attitudes. These shows provide evidence when contestants are making decisions over very large stakes, and in a replicated, structured way. Inferences are generally confounded by the subjective assessment of skill in some games, and the dynamic nature of the task in most games. We consider the game

Steffen Andersen; Glenn W. Harrison; Morten I. Lau; E. Elisabet Rutstrom

274

Drug Facts  

MedlinePLUS Videos and Cool Tools

... who wants to talk to her daughter about drugs. 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? ...

275

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

NASA Astrophysics Data System (ADS)

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

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

2012-02-01

276

Comparison of Attitudes, Knowledge and Drug Abuse Among Military Offenders  

ERIC Educational Resources Information Center

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

Ratliff, Bascom W.

1977-01-01

277

positions): transistor,  

E-print Network

scientists of the century'' (20 positions): . Technology ďż˝ 6 (airplane, rocket, TV, transistor, plastic, WWW project: ''The greatest scientists of the century'' (20 positions): . Technology ďż˝ 6 (airplane, rocket, TV unfriendly! #12; Why is excessive coding so bad for specific tasks? E#ciency is lost, which makes

Artemov, Sergei N.

278

Positive Psychotherapy  

ERIC Educational Resources Information Center

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

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

2006-01-01

279

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

E-print Network

:00 p.m. Mark 931-319-2205 $2 at gate Fair Must Ledford 931-823-4295 Limit 5 Control animals/ Goat Fee Must 5:30 p.m. Tracey 615-464-5229 Show Control Lawrence Goat 8/2/2013 Smith Co. 7/25/2013 Youth 3 of Show TN Exhibit. 11:00 a.m. to 4:00 p.m. John 931-684-5971 Limit 5 Region Entry Fee 4-12 grade 1:00 p

Grissino-Mayer, Henri D.

280

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

281

Drug-drug interaction through molecular structure similarity analysis  

PubMed Central

Background Drug–drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs. Methods We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. DrugBank was used as a resource for collecting 9454 established DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to identify DDI candidates. Results The methodology was evaluated using as a gold standard the interactions retrieved from the initial DrugBank database. Results demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision of 0.26. Additionally, the methodology was also evaluated in an independent test using the Micromedex/Drugdex database. Conclusion The proposed methodology is simple, efficient, allows the investigation of large numbers of drugs, and helps highlight the etiology of DDI. A database of 58?403 predicted DDIs with structural evidence is provided as an open resource for investigators seeking to analyze DDIs. PMID:22647690

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

2012-01-01

282

Drug Impact Index.  

ERIC Educational Resources Information Center

The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

Western Center for Drug-Free Schools and Communities.

283

Magic Carpet Shows Its Colors  

NASA Technical Reports Server (NTRS)

The upper left image in this display is from the panoramic camera on the Mars Exploration Rover Spirit, showing the 'Magic Carpet' region near the rover at Gusev Crater, Mars, on Sol 7, the seventh martian day of its journey (Jan. 10, 2004). The lower image, also from the panoramic camera, is a monochrome (single filter) image of a rock in the 'Magic Carpet' area. Note that colored portions of the rock correlate with extracted spectra shown in the plot to the side. Four different types of materials are shown: the rock itself, the soil in front of the rock, some brighter soil on top of the rock, and some dust that has collected in small recesses on the rock face ('spots'). Each color on the spectra matches a line on the graph, showing how the panoramic camera's different colored filters are used to broadly assess the varying mineral compositions of martian rocks and soils.

2004-01-01

284

Homelessness and drug misuse in developing countries: A mathematical approach  

NASA Astrophysics Data System (ADS)

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

Bhunu, C. P.

2014-06-01

285

Rocks and Minerals Slide Show  

NSDL National Science Digital Library

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

286

Identifying Drugs  

MedlinePLUS

... List View Paraphernalia View All Narcotics Stimulant Hallucinogens Cannabis Depressants Opioid Drugs of Concern Inhalants Steroids Drug ... sticks Needle Pacifier Pipe Rag Roach clip Rolling papers Small spoon Straw or tube About this Site ...

287

Drug Resistance  

MedlinePLUS

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

288

Club Drugs  

MedlinePLUS

Club drugs are group of psychoactive drugs. They act on the central nervous system and can cause changes ... bars. They include Methylenedioxymethamphetamine (MDMA), also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and ...

289

"Medicine show." Alice in Doctorland.  

PubMed

This is an excerpt from the script of a 1939 play provided to the Institute of Social Medicine and Community Health by the Library of Congress Federal Theater Project Collection at George Mason University Library, Fairfax, Virginia, pages 2-1-8 thru 2-1-14. The Federal Theatre Project (FTP) was part of the New Deal program for the arts 1935-1939. Funded by the Works Progress Administration (WPA) its goal was to employ theater professionals from the relief rolls. A number of FTP plays deal with aspects of medicine and public health. Pageants, puppet shows and documentary plays celebrated progress in medical science while examining social controversies in medical services and the public health movement. "Medicine Show" sharply contrasts technological wonders with social backwardness. The play was rehearsed by the FTP but never opened because funding ended. A revised version ran on Broadway in 1940. The preceding comments are adapted from an excellent, well-illustrated review of five of these plays by Barabara Melosh: "The New Deal's Federal Theatre Project," Medical Heritage, Vol. 2, No. 1 (Jan/Feb 1986), pp. 36-47. PMID:10301683

1987-01-01

290

Students' View Of School Drug Use  

ERIC Educational Resources Information Center

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

Farkas, Marshall I.

1974-01-01

291

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

292

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

293

Drug Survey.  

ERIC Educational Resources Information Center

Results of a survey of student perceptions of drugs and drug use that was conducted at Bowie State College are presented. Studies that have been conducted on college students' use of alcohol, marijuana, and cocaine in the last five years are reviewed, along with additional studies relating to the general population and the following drugs:…

Gill, Wanda E.; And Others

294

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

295

ORAL PRESENTATION Open Access Drug-dominated dopamine circuits spiral addicts  

E-print Network

of these actions be followed by punishment of magnitude -16 (the last 150 trials), then whereas cognitive loops a positive value to it). Keramati and Gutkin BMC Neuroscience 2012, 13(Suppl 1):O8 http by adding a positive term D to the prediction error signal. Simulation results (Figure 1) show that drug

Paris-Sud XI, Université de

296

Drug allergy  

PubMed Central

Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR) not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs. PMID:22165859

2011-01-01

297

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.

298

Acute adverse reactions to psychoactive drugs, drug usage, and psychopathology  

Microsoft Academic Search

Used a field survey method to examine the relationship between psychopathology and acute adverse reactions to psychoactive drugs. A paper-and-pencil measure of acute adverse reactions was developed and administered to 530 college students with drug-use experience. Acute adverse reactions were hypothesized to covary positively with regression, schizophrenia, and drug usage, and to covary negatively with adjustment and paranoia. These hypotheses

Murray P. Naditch

1974-01-01

299

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

300

GWAS and drug targets  

PubMed Central

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

2014-01-01

301

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

E-print Network

monthly Financial packages for both Wholesale and Retail divisions ?Complete monthly sales analysis in a Retail, Wholesale, and Manufacturing environment. ?Basic understanding and experience using JD Edwards and COGNOS/Powerplay ?Previous experience in a Finance or Accounting position within the US food industry

New Hampshire, University of

302

Are Illegal Drugs Inferior Goods?  

Microsoft Academic Search

Using data from the National Survey on Drug Use and Health, evidence of income inferiority in illegal drug consumption is presented. This is done by estimation of binary choice probit models with endogenous regressors. The simultaneity issue between drug consumption and income has been addressed by using a two-step estimation procedure. The results indicate that accounting for simultaneity shows income

Suryadipta Roy

2005-01-01

303

Alcohol, Drugs and Young Drivers.  

ERIC Educational Resources Information Center

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

Voas, Robert B.

304

Qualitative measurement of drugs.  

PubMed

It has been noted for several years that certain drugs produce abnormal test results in patients who are administered the electronystagmograph (ENG) test. Drug specific waveforms, termed drug evoked potentials (DEP), have been identified by using the ENG for alcohol, marijuana, cocaine, tranquilizers, amphetamines, barbiturates, opiates, hallucinogens, caffeine, aminophylline, dopamine, several gases and approximately 75 combinations of drugs (N = 821). Tests for double blind diagnosis of drug intake as well as tests for repeatability within the same subject were conducted. Subjects included surgical candidates, healthy volunteers, and neonates (N = 248). Drugs tested were ketamine hydrochloride, fentanyl, sodium pentothal, cocaine, dextroamphetamine, sodium seconal, morphine sulfate, phenobarbital, and meperidine. Placebos of dextrose in water and sucrose tablets were also used (N = 25). Analysis of the waveforms produced by surgical candidates and healthy volunteers revealed no false negatives or false positives. Analysis of waveforms produced by neonates whose mothers had been administered meperidine demonstrated a diminishing effect over the course of a 3 day period. Results of repeated studies revealed reliability within subject. One subject who was administered dextroamphetamine did not produce a wave consistent with amphetamine with a dosage of 5 mg. He did, however, produce an amphetamine wave when administered 10 mg of dextroamphetamine. These findings suggest a dose related effect, indicating the need for establishment of minimal levels of detection. Results indicate that with refinement and further research, this method could be used for identification of drugs diagnostically. PMID:6694484

Westerman, S T; Golz, A; Komorowski, F S; Gilbert, L M

1984-02-01

305

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

306

Drug Interactions  

Microsoft Academic Search

Regulatory review scientists have been interested in the impact of drug interactions on the safety and efficacy of drugs for\\u000a many years; however, a number of regulatory actions highlight the importance of the issue. The withdrawals of terfenadine,\\u000a astemizole, and cisapride were related, in part, to safety concerns when drug interactions with cytochrome P450 (CYP) 3A inhibitors\\u000a led to higher

Kellie Schoolar Reynolds

307

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

308

Probabilistic drug connectivity mapping  

PubMed Central

Background The aim of connectivity mapping is to match drugs using drug-treatment gene expression profiles from multiple cell lines. This can be viewed as an information retrieval task, with the goal of finding the most relevant profiles for a given query drug. We infer the relevance for retrieval by data-driven probabilistic modeling of the drug responses, resulting in probabilistic connectivity mapping, and further consider the available cell lines as different data sources. We use a special type of probabilistic model to separate what is shared and specific between the sources, in contrast to earlier connectivity mapping methods that have intentionally aggregated all available data, neglecting information about the differences between the cell lines. Results We show that the probabilistic multi-source connectivity mapping method is superior to alternatives in finding functionally and chemically similar drugs from the Connectivity Map data set. We also demonstrate that an extension of the method is capable of retrieving combinations of drugs that match different relevant parts of the query drug response profile. Conclusions The probabilistic modeling-based connectivity mapping method provides a promising alternative to earlier methods. Principled integration of data from different cell lines helps to identify relevant responses for specific drug repositioning applications. PMID:24742351

2014-01-01

309

Gene Positioning  

PubMed Central

Eukaryotic gene expression is an intricate multistep process, regulated within the cell nucleus through the activation or repression of RNA synthesis, processing, cytoplasmic export, and translation into protein. The major regulators of gene expression are chromatin remodeling and transcription machineries that are locally recruited to genes. However, enzymatic activities that act on genes are not ubiquitously distributed throughout the nucleoplasm, but limited to specific and spatially defined foci that promote preferred higher-order chromatin arrangements. The positioning of genes within the nuclear landscape relative to specific functional landmarks plays an important role in gene regulation and disease. PMID:20484389

Ferrai, Carmelo; de Castro, Ines Jesus; Lavitas, Liron; Chotalia, Mita; Pombo, Ana

2010-01-01

310

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

311

In vitro validation of drug-induced phospholipidosis.  

PubMed

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

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

2012-01-01

312

[Antidepressant drugs].  

PubMed

Depression is a disorder of mood that causes strong impact on the patient and his family's quality of life. The increasing number of cases and its social consequences have made depression a great public health problem. Some depressant patients develop suicide thoughts and may try suicide later. The disease occurs in all ages and its prevalence is of 7.4%. Women aged 15 to 29 are more likely to be affected, whereas people aged 50 or older are less affected. The presence of depression worsens the prognostic of other clinical conditions when compared to not depressant patients. This paper describes the main drugs used in the treatment of depression and correlates the drug with the neurobiology of the disease. Aiming the study of the pharmacologic and therapeutic characteristics of antidepressant drugs, a literature review was performed using electronic databases (Pubmed and Lilacs), papers and books related to the theme. The main antidepressant drugs are classified according to their chemical structure or their action on neurotransmitters. An important point in the therapy is the understanding of the pharmacokinetics of the drugs. The choice of the drug must consider the symptoms, the patient's age, other drugs in use, the history of pharmacological treatments and so forth. No drug is significantly better than the other in the treatment of depression. The important thing in choosing a drug is to have the best therapeutic response, the reduction of symptoms, a good adherence to therapy, few side effects and secure drug interaction. By understanding the use of these drugs, it will be possible to give the patient and his family a better quality of life. PMID:21672446

Aguiar, C Clayton; Castro, Thiago R; Carvalho, André F; Vale, Otoni C; Sousa, F Cléa; Vasconcelos, Silvânia M

2011-01-01

313

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

314

Drug Testing.  

ERIC Educational Resources Information Center

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

Legal Memorandum, 1987

1987-01-01

315

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.

316

New drug applications sought.  

PubMed

Three drug companies have submitted applications to the Food and Drug Administration (FDA) for expanded labeling of their products, including Bristol-Myers Squibb's d4T (Stavudine), Abbott Laboratories' clarithromycin (Biaxin), and Chiron Corporations's ganciclovir (intraocular Vitrasert). Approvals are being sought for stavudine's use in HIV-positive adults with CD4 counts between 50 and 500 who have been treated with at least 24 months of zidovudine; Biaxin's use for prevention of Mycobacterium avium complex in patients with advanced HIV infection; and Chiron's method of treating CMV retinitis. PMID:11362777

1995-09-01

317

Educational Outreach: The Space Science Road Show  

NASA Astrophysics Data System (ADS)

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

Cox, N. L. J.

2002-01-01

318

CMVO Drug Testing Program Request for Information  

E-print Network

CMVO Drug Testing Program Request for Information TO: RE: Name (First, M.I., Last) Social Security substances testing records. Please complete this form and return it to: University of Florida CMVO Drug or she has tested positive, or refused to test, on any pre-employment drug or alcohol test administered

Mazzotti, Frank

319

Psychological Status of Student Drug Users  

ERIC Educational Resources Information Center

This study was performed to determine how a child's self-concept influences their drug attitudes and behaviors. "Anti-Social Tendencies" and "Family Relations" correlated significantly and negatively with the use of almost all substances and positively with drug attitude. "Feeling of Belonging" was related negatively to the use of dangerous drugs.…

Galli, Nicholas; Stone, Donald R.

1975-01-01

320

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

321

Drug excipients.  

PubMed

The therapeutical use of drugs involves the application of dosage forms, serving as carrier systems together with several excipients to deliver the active ingredient to the site of action. Drug delivery technology combines an understanding of medicinal chemistry and pharmacology with the skill of formulation, aiming the preparation of improved pharmaceuticals. The recently introduced Biopharmaceutical Classification System provides guidance for dosage form design, taking the molecular and physico-chemical properties of drugs into consideration through their solubility and permeability characteristics. Pharmaceutical excipients used for oral dosage form have been traditionally assumed as being inert. However, recent experience and new results have shown that they can interact with the active drug ingredient, affecting its dissolution, absorption and bioavailability. Classification of the excipients is based on their role in the pharmaceutical formulation and on their interactions influencing drug delivery, based on their chemical and physico-chemical properties. The main classes are the antioxidants, coating materials, emulgents, taste- and smell-improvers, ointment bases, conserving agents, consistency-improvers and disintegrating materials. Some of the excipients may serve multiple purposes; for example, methylcellulose is a coating material, is applied in the preparation of suspensions, to increase viscosity, as a disintegrating agent or binder in tablets. The aim of this paper is to review the drug-excipients with respect to their chemistry, importance and interactions altering the pharmacokinetics of the drug substances. Emphasis will be given to two major classes of excipients: the antioxidants and disintegrants (substances facilitating disintegration of the drug tablets in the gastro-intestinal tract). Details will be given on the mechanisms through which they can alter drug effectiveness and tolerance, and control their application. Examples and references will be given for their analysis. PMID:17017910

Kalász, Huba; Antal, István

2006-01-01

322

Alterations in the processing of non-drug-related affective stimuli in abstinent heroin addicts.  

PubMed

Long-term exposure to drug may alter the neural system associated with affective processing, as evidenced by both clinical observations and behavioral data documenting dysfunctions in emotional experiences and processing in drug addicts. Although many imaging studies examined neural responses to drug or drug-related cues in addicts, there have been few studies explicitly designed to reveal their neural abnormalities in processing non-drug-related natural affective materials. The present study asked abstinent heroin addicts and normal controls to passively view standardized affective pictures of positive, negative, or neutral valence and compared their brain activities with functional MRI. Compared to normal controls, addicts showed reduced activation in right amygdala in response to the affective pictures, consistent with previous reports of blunted subjective experience for affective stimuli in addicts. Furthermore, in two visual cortical areas BA 19 and 37, while the controls showed greater responses to positive pictures than to negative ones replicating literature findings, the addicts showed the opposite pattern. The results reveal a complex pattern of altered processing of non-drug-related affective materials in addicts showing both heightened and blunted neural responses in different brain regions and for different stimulus valence. The present study highlights the importance of brain imaging research on drug addicts' processing of affective stimuli in understanding disruptions in their emotion circuitry. PMID:19683582

Wang, Zhao-Xin; Zhang, John X; Wu, Qiu-Lin; Liu, Ning; Hu, Xiao-Ping; Chan, Raymond C K; Xiao, Zhuang-Wei

2010-01-01

323

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.

324

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

325

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 ...

326

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

327

Towards better patient care: drugs to avoid.  

PubMed

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

2013-04-01

328

Drug Interactions  

MedlinePLUS

... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

329

Why drugs?  

Microsoft Academic Search

Drug therapy for obesity has had a difficult past history. A number of drugs have had addictive or toxic properties that have\\u000a required discontinuation. Pharmacotherapy for obesity has an important role in those persons who have failed behavioral weight\\u000a loss attempts or as an adjunct to those attempts. The interest in pharmacotherapy for obesity is an outgrowth of the now

F. Xavier Pi-Sunyer

330

In silico modeling to predict drug-induced phospholipidosis.  

PubMed

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

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

2013-06-01

331

21 CFR 890.3110 - Electric positioning chair.  

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

2014-04-01

332

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

333

21 CFR 890.3110 - Electric positioning chair.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

334

4. VIEW, LOOKING SOUTHWEST, SHOWING TIMBER PILL APPROACH SPAN AND ...  

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

4. VIEW, LOOKING SOUTHWEST, SHOWING TIMBER PILL APPROACH SPAN AND BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Shaw's Cove Bridge, Spanning Shaw's Cove, New London, New London County, CT

335

36. INTERIOR VIEW, BERK SWITCH TOWER, SOUTH NORWALK, SHOWING SWITCHING ...  

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

36. INTERIOR VIEW, BERK SWITCH TOWER, SOUTH NORWALK, SHOWING SWITCHING LEVERS FROM OPERATOR'S POSITION - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT

336

6. VIEW FROM WESTERN ABUTMENT, SHOWING SIDE ELEVATION OF BRIDGE ...  

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

6. VIEW FROM WESTERN ABUTMENT, SHOWING SIDE ELEVATION OF BRIDGE No. Z-6 IN OPEN POSITION. - Chicago, Milwaukee & St. Paul Railway, Bridge No. Z-6, Spanning North Branch of Chicago River, South of Cortland Street, Chicago, Cook County, IL

337

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

338

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

PubMed Central

Rational: Research suggests that increased consumption of herbal drugs is raising important public health concerns such as safety issues that may involve adverse effects and herb-drug interactions. The main objective of this study is to investigate the role of Pharmacists in herbal drug information dissemination. Method: We investigated the demographics, knowledge, attitude and practices regarding herbal drug information and regulatory laws among Pharmacists living in the six (6) States that constitute the Niger-Delta region of Nigeria. A total of 300 self-administered questionnaires were distributed to Pharmacists aged 21 years and above. Findings: About half of the respondents (48.72 %) were Hospital based Pharmacists. Knowledge of herbal drugs was 46.33 % while 64 .0 % showed positive attitude towards its use. Most of the information on herbal drugs were sourced from the internet (23.08 %) while 53.48 % were aware of the laws and regulations controlling herbal drugs in Nigeria. 88.64 % were in favour of the establishment of a National Herbal Drug Research and Development Agency and 55.68 % strongly agreeing to the setting up of a Herbal Drug Information Centre. Conclusion: The availability of herbal drug information services will not only enhance the performance of the Pharmacists, but will also add value to the life of the patients. PMID:24826042

Atavwoda, Abere Tavs; Gabriel, Aina Ayodele

2012-01-01

339

A Beam Position Stabilization System  

Microsoft Academic Search

We describe a simple closed loop system for beam position stabilization on an electron storage ring. The system using a differential photoresistive cell for the beam position detector reacts on the beam through appropriate dipole correctors. Typical sensitivity of this cell is 10 mV per micron with less than one mV noise. Results obtained on ACO show that the position

M. Bergher

1979-01-01

340

Utilising Discursive Positioning in Counselling  

ERIC Educational Resources Information Center

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

Winslade, John M.

2005-01-01

341

The controversial Alabang Case has stimulated a renewed interest in the illegal drug problem by all sectors of society. The Philippine Drug Enforcement Agency welcomes this as a positive indicator that we are headed towards the right direction in solving this age-old social malady. PDEA Director General\\/Senior Undersecretary DIONISIO R. SANTIAGO  

Microsoft Academic Search

These programs will incorporate the activation and strengthening of the Anti-Drug Abuse Councils in coordination with the local police, who are under the direct control and supervision of local officials. The DILG Memorandum Circular also incorporates efforts to address the issue of Narco-Politics, especially since local and national elections are just around the corner. The PDEA Chief clarified that based

DIONISIO R. SANTIAGO

342

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

343

Temperature Data Shows Warming in 2001  

NASA Technical Reports Server (NTRS)

TThe figure above depicts how much air temperatures near the Earth's surface changed relative to the global mean temperature from 1951 to 1980. NASA researchers used maps of urban areas derived from city lights data to account for the 'heat island' effect of cities. The red and orange colors show that temperatures are warmer in most regions of the world when compared to the 1951 to 1980 'normal' temperatures. Warming around the world has been widespread, but it is not present everywhere. The largest warming is in Northern Canada, Alaska and Siberia, as indicated by the deeper red colors. The lower 48 United States have become warmer recently, but only enough to make the temperatures comparable to what they were in the 1930s. The scale on the bottom of these temperature anomaly images represent degrees in Celsius. The negative numbers represent cooling and the positive numbers depict warming. Overall, the air temperature near the Earth's surface has warmed by 1oF (0.6oC) globally, on average, over the last century. For more information and additional images, read Satellites Shed Light on a Warmer World. Image courtesy Goddard Institute for Space Studies (GISS).

2002-01-01

344

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

345

Information for Consumers (Drugs)  

MedlinePLUS

... in My Home (MIMH) Recalls & Alerts Drug Safety Communications Drug Alerts and Statements Drug Recalls Stay Connected FDA on Facebook and Flickr FDA YouTube Channel (Drugs) FDA Video Gallery Drug Information on Twitter ...

346

[Etravirine drug interactions].  

PubMed

Etravirine (ETR) belongs to the family of non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs), with antiviral activity in patients with resistance to first-generation NNRTIs. The drug interactions caused by ETR are due to its dual effect on the CYP450 system. ETR acts as an inducer of CYP3A4 and inhibitor of CYP2C9 and CYP2C19. This drug shows few clinically significant drug interactions, the most important of which involve the unboosted protease inhibitors, the NNRTIs efavirenz and nevirapine, full-dose ritonavir and tipranavir/ritonavir. Interaction with fosamprenavir/ritonavir is not clinically significant, although their plasma levels vary slightly when used in combination with ETR. ETR shows no interactions with darunavir/ritonavir. PMID:20116625

Pérez, Vicente Estrada; Sánchez-Parra, Clara; Serrano Villar, Sergio

2009-12-01

347

Mitochondrial drugs.  

PubMed

Mitochondria are cellular organelles that perform pivotal functions essential for ATP production, homeostasis, and metabolism. Moreover, mitochondria are integral to a variety of cell death and survival pathways. These roles identify mitochondria as a potential target for drugs to treat metabolic and hyperproliferative diseases. Differences in the redox state of pathogenic versus non-pathogenic cells may be exploited to achieve selective anti-proliferative and cytotoxic activity against target cell populations. Pro-oxidant drugs, such as Trisenox and Elesclomol, are demonstrating clinical utility in the treatment of cancer. Results obtained with Bz-423 in mice demonstrate the potential for mitochondria-targeted drugs to control disorders of immune function. Research associating an elevated oxidant state with mitochondrial damage, degenerative disease, and aging dictates the need for a better understanding of when and how pharmacological manipulation of mitochondrial function provides most therapeutic benefit. PMID:18602018

Toogood, Peter L

2008-08-01

348

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.

349

Juvenile Crime and Drug Abuse  

Microsoft Academic Search

Results from an ongoing, longitudinal study of juvenile detainees focusing on the relationship between their drug use and delinquency\\/crime, are summarized. Three hundred and ninety-nine youths were first interviewed in 1986\\/87, and 41 percent were found to be urine positive for recent drug use at the time of detention. We reinterviewed 305 of the youths approximately one year later, and

Richard Dembo; Linda Williams; James Schmeidler; Eric D. Wish; Alan Getreu; Estrellita Berry

1992-01-01

350

DrugComboRanker: drug combination discovery based on target network analysis  

PubMed Central

Motivation: Currently there are no curative anticancer drugs, and drug resistance is often acquired after drug treatment. One of the reasons is that cancers are complex diseases, regulated by multiple signaling pathways and cross talks among the pathways. It is expected that drug combinations can reduce drug resistance and improve patients’ outcomes. In clinical practice, the ideal and feasible drug combinations are combinations of existing Food and Drug Administration-approved drugs or bioactive compounds that are already used on patients or have entered clinical trials and passed safety tests. These drug combinations could directly be used on patients with less concern of toxic effects. However, there is so far no effective computational approach to search effective drug combinations from the enormous number of possibilities. Results: In this study, we propose a novel systematic computational tool DrugComboRanker to prioritize synergistic drug combinations and uncover their mechanisms of action. We first build a drug functional network based on their genomic profiles, and partition the network into numerous drug network communities by using a Bayesian non-negative matrix factorization approach. As drugs within overlapping community share common mechanisms of action, we next uncover potential targets of drugs by applying a recommendation system on drug communities. We meanwhile build disease-specific signaling networks based on patients’ genomic profiles and interactome data. We then identify drug combinations by searching drugs whose targets are enriched in the complementary signaling modules of the disease signaling network. The novel method was evaluated on lung adenocarcinoma and endocrine receptor positive breast cancer, and compared with other drug combination approaches. These case studies discovered a set of effective drug combinations top ranked in our prediction list, and mapped the drug targets on the disease signaling network to highlight the mechanisms of action of the drug combinations. Availability and implementation: The program is available on request. Contact: stwong@tmhs.org PMID:24931988

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

2014-01-01

351

Magic, Monsters, and Movies: Americas Midnight Ghost Shows  

Microsoft Academic Search

This essay examines midnight ghost shows (alternately known as “spook shows,” or “spookers”) and seeks to reinsert them into theatre history and to posit them as a cultural barometer of the time in which they were popular. Ghost shows were magic shows presented on the stages of America’s movie theatres throughout the first half of the twentieth century. A ghost

Beth A. Kattelman

2010-01-01

352

were made from the oligonucleotide positive retina, in which most RGCs showed strong fluorescence.  

E-print Network

depression in simple neural networks. Nature 388, 439­448 (1997). 2. Tao, H. W., Zhang, L. I., Bi, G. Q. Neurosci. 20, 3233­3243 (2000). 3. Rumelhart, D. E., Hinton, G. E. & Williams, R. J. Learning representations by back-propagation errors. Nature 323, 533­536 (1986). 4. Cohen-cory, S. & Fraser, S. E. BDNF

Cai, Long

353

Sickle Cell Crisis Associated with Drugs.  

National Technical Information Service (NTIS)

Drug overdose precipitated sickle cell crisis leading to death in four cases. Toxicologic studies in life and postmortem examinations showed the deaths to be caused by a combination of the ingested drugs and associated sickle cell crisis. Both the homozyg...

C. Delage, F. G. Mullick, N. S. Irey

1972-01-01

354

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

355

Drug residues.  

PubMed

The use of veterinary drugs in animal production is necessary for the prevention and treatment of disease; however, such use may result in residues. Regulatory authorities administer legislative frameworks which ensure that foods derived from animals treated with approved veterinary drugs are safe for human consumption. A human food safety evaluation is conducted as follows: it estimates the risk to human health and safety--based on scientific assessment of the available information and data--formulates measures for controlling the risks identified, and communicates the findings and implications of the risk assessment to interested parties. Foods derived from animals are monitored for the presence of drug residues. The reported incidence of illegal residues from these programmes is very low. These findings reassure the public that veterinary drugs are effectively regulated and that food obtained from treated animals does not contain residues that might constitute a health hazard to consumers. Non-regulatory organizations, including the veterinary pharmaceutical industry, producer organisations, veterinarians and food processors, all contribute to a safe food supply. The food safety risk analysis framework is continually refined to ensure that the health of all consumers is protected. PMID:20204591

Reeves, Philip T

2010-01-01

356

Drug Filtering  

NSDL National Science Digital Library

In this math meets health science activity, learners observe a model of exponential decay, and how kidneys filter blood. Learners will calculate the amount of a drug in the body over a period of time. Then, they will make and analyze the graphical representation of this exponential function. This lesson guide includes questions for learners, assessment options, extensions, and reflection questions.

Iles, Lawrence F.

2010-01-01

357

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.

358

The War on Illegal Drugs  

Microsoft Academic Search

This paper develops a simple model of the war against illegal drugs in producer and consumer countries. The analysis shows how the equilibrium quantity of illegal drugs, as well as their price, depend on key parametres of the model such as the price elasticity of demand and the effectiveness of the resources allocated to enforcement and prevention and treatment policies.

Daniel Mejía

359

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

360

Psychophysiological prediction of choice: relevance to insight and drug addiction  

PubMed Central

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

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

2012-01-01

361

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.

362

New FDA rules force drug makers to detail youth-specific effects. Food and Drug Administration.  

PubMed

The U.S. Food and Drug Administration (FDA) has issued new rules requiring pharmaceutical companies to provide doctors with information on the effects of drugs on children. In addition, rules allow the FDA to require testing of certain drugs on children under "compelling circumstances." The FDA issued the regulations after complaints from parents of HIV-positive children, because of the lack of drug studies on children under 18 years. PMID:11367188

1999-01-01

363

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

364

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

PubMed

In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4'-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes' stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats' retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes. PMID:24960297

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

2014-07-11

365

Pharmacogenetics of anxiolytic drugs  

Microsoft Academic Search

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

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

2009-01-01

366

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.

367

Religiosity and Drug Use among Inmates in Boot Camp: Testing a Theoretical Model with Reciprocal Relationships.  

ERIC Educational Resources Information Center

Examines the effects of religiosity within a theoretical model with reciprocal relationships of drug use among boot camp inmates. Findings show that attachment to caregivers is inversely related to associations with peers who engage in illicit behavior, whereas being abused by an adult is positively related to these associations. These…

Benda, Brent B.; Toombs, Nancy J.

2002-01-01

368

Some current studies of psychoactive and hallucinogenic drug use  

Microsoft Academic Search

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

Reginald G. Smart

1970-01-01

369

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

370

Photomechanical drug delivery  

NASA Astrophysics Data System (ADS)

Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

Doukas, Apostolos G.; Lee, Shun

2000-05-01

371

Post-traumatic stress disorder, drug dependence, and suicidality among male Vietnam veterans with a history of heavy drug use.  

PubMed

This study examines the roles of post-traumatic stress disorder (PTSD) and drug dependence in non-fatal suicidality, i.e., suicidal ideation and suicide attempt, among Vietnam veterans in their adult years. The sample includes male veterans deployed to Vietnam, including an oversample of those who tested positive for opiates at their return (n = 642). PTSD, substance abuse, suicidality, and other psychopathology are analyzed using three waves of survey and military data covering the time period from early adolescence to middle adulthood. Measures include the onset and recency of each of the lifetime DSM-IV PTSD symptom criteria, and yearly symptom measures of DSM-IV dependence for alcohol and eight classes of psychoactive substances. Survival and hazard models are applied to assess the effects of drug dependence, PTSD, and other psychopathology on the duration of suicidality. Longitudinal models estimate the casual relationships among PTSD, drug dependence, and suicidality over a 25-year period. Results show evidence of strong continuity of PTSD, drug dependence, and suicidality over time. The causal role of drug dependence on PTSD and suicidality is limited to young adulthood. Evidence is stronger for self-medication in later adulthood. The results indicate that a life course perspective is needed for the combined treatment of PTSD and drug dependence for severely traumatized populations. PMID:15555815

Price, Rumi Kato; Risk, Nathan K; Haden, Ashley H; Lewis, Collins E; Spitznagel, Edward L

2004-12-01

372

Drug Filtering  

NSDL National Science Digital Library

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

2010-12-06

373

Psychosocial predictors of needle sharing among intravenous drug users.  

PubMed

This study examined the relationship between health beliefs and needle sharing in a sample of 226 heroin detoxification clients. Zero-order correlations revealed that needle sharing was positively associated with perceived susceptibility and AIDS anxiety, and negatively associated with self-efficacy and communication skill in negotiating safe needle practices. Logistic regression analysis showed that demographic and situational factors also play a role in needle sharing. White race and injection of drugs in shooting galleries or other public places increase the odds of sharing a "dirty" needle, while that probability decreases sharply as a function of drug users' self-efficacy. This last finding suggests that preventive clinical interventions such as counseling or psychoeducational groups maybe needed to help drug users develop confidence in resisting needle sharing. PMID:8407025

Gibson, D R; Choi, K H; Catania, J A; Sorensen, J L; Kegeles, S

1993-08-01

374

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.  

PubMed

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. PMID:25155439

Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

2014-10-01

375

Drug Use and Medication Adherence among HIV1 Infected Individuals  

Microsoft Academic Search

This longitudinal study examined the impact of drug use and abuse on medication adherence among 150 HIV-infected individuals,\\u000a 102 who tested urinalysis positive for recent illicit drug use. Medication adherence was tracked over a 6-month period using\\u000a an electronic monitoring device (MEMS caps). Over the 6-month study drug-positive participants demonstrated significantly\\u000a worse medication adherence than did drug-negative participants (63 vs.

Charles H. Hinkin; Terry R. Barclay; Steven A. Castellon; Andrew J. Levine; Ramani S. Durvasula; Sarah D. Marion; Hector F. Myers; Douglas Longshore

2007-01-01

376

Drug safety sciences and the bottleneck in drug development.  

PubMed

During a recent review of a new drug application for treatment of a chronic disease, US Food and Drug Administration (FDA) regulators agreed with the sponsor's assessment of efficacy. However, it was noted that two subjects receiving active treatment experienced abnormal liver chemistries that possibly, but not definitely, indicated a liver safety liability. The sponsor was told that a prerequisite for approval would be a new clinical trial involving 20,000 patients treated for 1 year, with 10,000 receiving the new drug and 10,000 receiving a comparator treatment. The sponsor is now faced with the substantial costs involved in undertaking such a large study, the loss of patent life during the conduct and analysis of the study, and the prospect of losing in-class market position. If the drug is ultimately approved, this detour will result in costs and potential revenue loss to the sponsor of well over $1 billion. PMID:21593756

Watkins, P B

2011-06-01

377

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 ...

378

Recreational Drugs and HIV  

MedlinePLUS

... DRUG USE AND HIV DISEASE DRUG INTERACTIONS THE BOTTOM LINE FOR MORE INFORMATION HOW DOES RECREATIONAL DRUG USE ... protease inhibitors may increase effect of marijuana. THE BOTTOM LINE Some recreational drugs may interact with some ARVs. ...

379

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

380

Drugs in College  

E-print Network

on Drug Abuse. Prescription Drug Abuse. MedlinePlus. 2008.June 5, 2006. Abuse of Prescription Drugs Fuelled by Onlineabuse and the three most common drugs used by col- lege students are alcohol, marijuana, and prescription

Yang, Joy

2009-01-01

381

Drugs Approved for Leukemia  

Cancer.gov

This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

382

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.

383

Drugs Approved for Neuroblastoma  

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

384

In vitro drug release mechanism and drug loading studies of cubic phase gels.  

PubMed

Glyceryl monooleate/water cubic phase systems were investigated as drug delivery systems, using salicylic acid as a model drug. The liquid crystalline phases formed by the glyceryl monooleate (GMO)/water systems were characterized by polarizing microscopy. In vitro drug release studies were performed and the influences of initial water content, swelling and drug loading on the drug release properties were evaluated. Water uptake followed second-order swelling kinetics. In vitro release profiles showed Fickian diffusion control and were independent on the initial water content and drug loading, suggesting GMO cubic phase gels suitability for use as drug delivery system. PMID:15778062

Lara, Marilisa G; Bentley, M Vitória L B; Collett, John H

2005-04-11

385

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.

386

[Emergent drugs (I): smart drugs].  

PubMed

In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects. PMID:21904408

Burillo-Putze, G; Díaz, B Climent; Pazos, J L Echarte; Mas, P Munné; Miró, O; Puiguriguer, J; Dargan, P

2011-01-01

387

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

388

Novel antibiotics targeting respiratory ATP synthesis in Gram-positive pathogenic bacteria.  

PubMed

Emergence of drug-resistant bacteria represents a high, unmet medical need, and discovery of new antibacterials acting on new bacterial targets is strongly needed. ATP synthase has been validated as an antibacterial target in Mycobacterium tuberculosis, where its activity can be specifically blocked by the diarylquinoline TMC207. However, potency of TMC207 is restricted to mycobacteria with little or no effect on the growth of other Gram-positive or Gram-negative bacteria. Here, we identify diarylquinolines with activity against key Gram-positive pathogens, significantly extending the antibacterial spectrum of the diarylquinoline class of drugs. These compounds inhibited growth of Staphylococcus aureus in planktonic state as well as in metabolically resting bacteria grown in a biofilm culture. Furthermore, time-kill experiments showed that the selected hits are rapidly bactericidal. Drug-resistant mutations were mapped to the ATP synthase enzyme, and biochemical analysis as well as drug-target interaction studies reveal ATP synthase as a target for these compounds. Moreover, knockdown of the ATP synthase expression strongly suppressed growth of S. aureus, revealing a crucial role of this target in bacterial growth and metabolism. Our data represent a proof of principle for using the diarylquinoline class of antibacterials in key Gram-positive pathogens. Our results suggest that broadening the antibacterial spectrum for this chemical class is possible without drifting off from the target. Development of the diarylquinolines class may represent a promising strategy for combating Gram-positive pathogens. PMID:22615276

Balemans, Wendy; Vranckx, Luc; Lounis, Nacer; Pop, Ovidiu; Guillemont, Jérôme; Vergauwen, Karen; Mol, Selena; Gilissen, Ron; Motte, Magali; Lançois, David; De Bolle, Miguel; Bonroy, Kristien; Lill, Holger; Andries, Koen; Bald, Dirk; Koul, Anil

2012-08-01

389

Meeting Drug Information Needs of Adolescents.  

ERIC Educational Resources Information Center

Drugs are an important life concern of adolescents, yet statistics show alarming and disturbing increases internationally in drug abuse. This paper reports on research that examines how adolescents cognitively process information about drugs. Four 17-year-old girls at a Catholic college in Sydney, Australia participated in a two-phase experiment…

Todd, Ross J.

390

Drug Usage Trends Among College Students  

ERIC Educational Resources Information Center

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

Girdano, Daniel A.; Girdano, Dorothy Dusek

1974-01-01

391

Disturbance of Calcium Metabolism by Anticonvulsant Drugs  

Microsoft Academic Search

A survey of calcium metabolism in epileptic patients in a residential centre showed a subnormal serum calcium level in 22·5% of patients and a raised alkaline phosphatase in 29%. Hypocalcaemia was related to high dosage of anticonvulsant drugs, to multiple drug therapy, and to the use of individual anticonvulsant drugs in the following order, with decreasing order of importance: pheneturide,

A. Richens; D. J. F. Rowe

1970-01-01

392

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

393

Antiplatelet Drugs  

PubMed Central

The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

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

2012-01-01

394

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.

395

Drug Abuse - Now.  

ERIC Educational Resources Information Center

A review of all facets of the drug abuse problem is offered in this anthology of articles. Moral dilemmas of physicians operating treatment programs are presented at one end of the spectrum and problems of the mass media and education about drug abuse are at the other. Drugs in the military, drugs in the ghettoes, drugs in the work place, and drug

Blachly, P. H., Ed.

396

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

397

A Drug Interactions Elective Course  

PubMed Central

Objectives To evaluate the impact of a drug interactions elective course on student knowledge and skills. Design A drug interactions elective which focused on assessment and application of drug interaction information and identification and management of commonly encountered drug interactions by therapeutic category was offered to third-year PharmD students. Students were expected to (1) determine whether a given interaction was clinically significant or required pharmacist intervention, and (2) make rational, scientifically sound, practical recommendations for management of drug interactions. Evaluation and Assessment Assessment included course evaluations, student self-assessments, and knowledge and skills assessments. Students who completed the course were more confident in their abilities relating to drug interactions than students who did not complete the course. Students who completed the course scored significantly better in all areas of the assessment compared to students who did not complete the course. Course evaluation results were also positive. Conclusion A course devoted to the identification and management of drug interactions improved PharmD students' knowledge and skills and could potentially improve the patient care they provide in the future. PMID:19657505

2009-01-01

398

Drug resistance pattern and associated risk factors of tuberculosis patients in the central province of Iran  

PubMed Central

Background: One of the fundamental issues of infectious disease treatment is drug resistance. The aim of the present study was to investigate the first-line anti-tuberculosis drug resistance rates and determine the risk factors related to multidrug resistant mycobacterium tuberculosis. Methods: From March 2011 to September 2012, mycobacterial strains were collected from one hundred fifteen diagnosed smear positive patients in the central province of Iran and tested for drug susceptible against ethambutol, rifampicin, isoniazid and streptomycin and the risk factors influencing the development of drug resistance were determined. Results: The mean age of patients was 52.23±19.75 years. The rate of multi-drug resistant tuberculosis (MDR-TB) was 7.8%. Our study revealed that there were significant associations between prior treatment, age < 45 years, positive smear result at the end of the second month and positive smear result at the end of the third month. However, there was no association found between gender, inhabitant, nationality, close contact with TB patient, HIV infection and size of mantoux test. Conclusion: The results show that about 8% of TB cases in Arak are MDR TB. The age under 45 years, previous TB treatment and positive smear at the end of the second and third months of treatment were the main factors in the development of MDR-TB. PMID:24294475

Farazi, Aliasghar; Sofian, Masoomeh; Zarrinfar, Nader; Katebi, Fatemeh; Hoseini, Seyed Davood; Keshavarz, Roohollah

2013-01-01

399

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

PubMed

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we aimed to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, ?9-tetrahydrocannabinol (THC), on tasks of relevance to the cognitive and positive symptoms of schizophrenia. The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. Adult control and DVD-deficient rats were injected with THC (0, 0.3, 0.6, 1.25, 2.5 mg/kg) 15 min before a delay match to sample (DMTS) task using variable delays (0-24 s). A separate group of rats was injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response or in the open field. Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was observed at 2.5 mg/kg for all delays (0-24 s). DVD-deficient rats showed THC-induced enhancement of PPI, which was not observed in control rats. There was no effect of maternal diet on acoustic startle response or locomotor responses in the open field. This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on sensitivity to the behavioural effects of cannabinoids. PMID:24776491

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

2014-06-01

400

Marijuana and the Use of Other Drugs  

Microsoft Academic Search

IT is well established that the use of marijuana by young people is positively correlated with at least the experimental use of other drugs1. The probability that an individual uses the strong hallucinogens such as LSD and other drugs rises sharply with increasing frequency of marijuana use2. Such associations are not, of course, sufficient to establish causal relationships between the

William McGlothlin; Kay Jamison; Steven Rosenblatt

1970-01-01

401

Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions  

PubMed Central

Background Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers. Methods We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling. Results Of the 5 × 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses. Conclusion We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases. PMID:24101737

Schmidt, Linnéa; Kling, Teresia; Monsefi, Naser; Olsson, Maja; Hansson, Caroline; Baskaran, Sathishkumar; Lundgren, Bo; Martens, Ulf; Häggblad, Maria; Westermark, Bengt; Forsberg Nilsson, Karin; Uhrbom, Lene; Karlsson-Lindahl, Linda; Gerlee, Philip; Nelander, Sven

2013-01-01

402

47 CFR 90.505 - Showing required.  

Code of Federal Regulations, 2010 CFR

...CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Developmental Operation § 90.505 Showing...showing that: (1) The applicant has an organized plan of development leading to a specific objective; (2) The actual...

2010-10-01

403

47 CFR 90.505 - Showing required.  

Code of Federal Regulations, 2011 CFR

...CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Developmental Operation § 90.505 Showing...showing that: (1) The applicant has an organized plan of development leading to a specific objective; (2) The actual...

2011-10-01

404

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

405

End-of-Semester Barbecue Talent Show  

E-print Network

Highlights End-of-Semester Barbecue Talent Show Scholarship Winners St. Francis Food Drive Ceremony. Details will be in next week's Weekly. Talent Show Dress Rehearsal Dress Rehearsal: All acts MUST come to the dress rehearsal before the Talent Show but don't miss class! Bring money for pizza. When

Pilyugin, Sergei S.

406

Inside Gun Shows What Goes On  

E-print Network

Preface 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 a great public institution. He was right. #12;Contents Preface Executive Summary Gun Shows in Context How

Leistikow, Bruce N.

407

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.

408

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

409

Outcome Trajectories in Drug Court: Do All Participants Have Drug Problems?  

PubMed Central

Graduation rates in drug courts average 50% to 70%, but it is unclear what proportion of graduates responded to the drug court services and what proportion might not have had serious drug problems upon entry. This study cluster-analyzed urine drug screen results during the first 14 weeks of treatment on 284 participants from three misdemeanor drug courts. A four-cluster solution (R2 > .75) produced distinct subgroups characterized by (1) consistently drug-negative urine specimens (34% of the sample), (2) consistently drug-positive specimens (21%), (3) consistently missed urine specimens (26%), and (4) urine specimens that began as drug-positive but became progressively drug-negative over time (19%). These data suggest that approximately one-third of the participants might not have had serious drug problems upon entry. Approximately one-fifth appeared to respond to drug court services, and nearly one-half continued to exhibit problems after 14 weeks. Implications for adaptive programming in drug courts are discussed. PMID:22081732

DeMatteo, David; Marlowe, Douglas B.; Festinger, David S.; Arabia, Patricia L.

2011-01-01

410

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

411

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

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

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

412

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

413

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

414

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

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

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

415

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

416

Project risk evaluation with design of experiment: A case of developing a generic drug analytic method development project  

Microsoft Academic Search

Generic drugs are equivalent to  branded drugs but at a cheaper price. The generic drug market is highly competitive and the drug companies tend to improve their market position by being first in the market when the patent on an original drug elapses. It is because if a company gets the first approval from Food and Drug Administration (FDA), 6

Hen-Yi Jen; Ying-Liang Liu

2012-01-01

417

Intracochlear Drug Delivery Systems  

PubMed Central

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

Borenstein, Jeffrey T.

2011-01-01

418

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

419

Systematic Drug Repositioning Based on Clinical Side-Effects  

Microsoft Academic Search

Drug repositioning helps fully explore indications for marketed drugs and clinical candidates. Here we show that the clinical side-effects (SEs) provide a human phenotypic profile for the drug, and this profile can suggest additional disease indications. We extracted 3,175 SE-disease relationships by combining the SE-drug relationships from drug labels and the drug-disease relationships from PharmGKB. Many relationships provide explicit repositioning

Lun Yang; Pankaj Agarwal

2011-01-01

420

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

421

[Antiplatelet drugs].  

PubMed

Antiplatelet therapy is widely used with proven benefit for the prevention of further ischemic complications in patients with coronary heart disease and stroke. Treatment guidelines for acute coronary syndrome and percutaneous coronary intervention now recommend the use of oral antiplatelet agents including clopidogrel in combination with aspirin (dual antiplatelet therapy: DAPT) for the prevention of recurrent ischemic events. The limitations of DAPT with clopidogrel include the potential for low response to clopidogrel identified through platelet reactivity or genetic testing, or slower return to normal platelet activity in patients who received clopidogrel prior to emergent or planned surgical procedures. This review will discuss the pharmacologic properties and clinical studies about new antiplatelet drugs including prasugrel, ticagrelor and PAR-1 inhibitors. PMID:25163316

Nishikawa, Masakatsu

2014-07-01

422

The Prediction of Growth-inhibitory Drug Combinations Showing Enhanced Differential Toxicity and Collateral Sensitivity  

Microsoft Academic Search

SUMMARY The possible application to chemotherapy of factors affecting the regulatory sys tems of cells has been considered. The extensive coordinate changes in intracellular enzyme concentrations which result from exposure to compounds interfering with the normal regulatory mechanisms suggest the possibility of combination therapy based upon the selective induction of quantitative changes in enzymatic activities. Such approaches would appear to

KENNETH PAIGEN

1962-01-01

423

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

424

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

MedlinePLUS

... PCR and Other Molecular Assays for Diagnosis of Influenza Virus Infection Clinical Signs and Symptoms of Influenza International ... Assessment and Biosafety Level Recommendations Highly Pathogenic Avian Influenza A (H5N1) Virus H5N1 In Birds and Other Animals H5N1 In ...

425

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.

426

[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

427

Drug abuse.  

PubMed

The wide array of therapeutic responses to substance use/abuse suggests that there is not one best approach to solve the problems of any one adolescent or young adult. Indeed, most young people require a variety of therapeutic interventions, which may include inpatient treatment, ambulatory therapeutic groups, and individual counseling, as well as self-help groups. In choosing a therapeutic program, the physician must be circumspect when interpreting the reported success or "cure" rates of any of these modalities. Such citations often are misleading because frequently they fail to reflect accurately the therapeutic influence of several important patient population variables that distinguish the programs. For example, an outpatient program may report better "cure" rates than an inpatient program because the ambulatory program may have enrolled clients who have more limited substance use patterns and who are more committed to abstinence. Furthermore, there is no standard methodology for reporting "rates of success." Some programs simply report a compliance rate for clients who attend meetings or scheduled therapeutic sessions, some report the numbers of clients who complete the program without any reference to recidivism, and some report the numbers of clients who are "drug-free" after 1 year. Given these caveats, the experience of most clinicians suggests that many adolescents who experiment with the traditional "gateway" drugs (eg, tobacco, alcohol, marijuana) respond well to outpatient group and individual therapy, those adolescents committed to a substance use/abuse pattern respond best to inpatient or residential programs, and adolescents who have a psychiatric/behavioral problem complicated by substance use/abuse require formal psychiatric treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7753735

Johnson, R L

1995-05-01

428

Drug disposition and drug-drug interaction data in 2013 FDA new drug applications: a systematic review.  

PubMed

The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. PMID:25271211

Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle

2014-12-01

429

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.

430

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

PubMed

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

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

2014-03-01

431

Automatic construction of a large-scale and accurate drug-side-effect association knowledge base from biomedical literature.  

PubMed

Systems approaches to studying drug-side-effect (drug-SE) associations are emerging as an active research area for drug target discovery, drug repositioning, and drug toxicity prediction. However, currently available drug-SE association databases are far from being complete. Herein, in an effort to increase the data completeness of current drug-SE relationship resources, we present an automatic learning approach to accurately extract drug-SE pairs from the vast amount of published biomedical literature, a rich knowledge source of side effect information for commercial, experimental, and even failed drugs. For the text corpus, we used 119,085,682 MEDLINE sentences and their parse trees. We used known drug-SE associations derived from US Food and Drug Administration (FDA) drug labels as prior knowledge to find relevant sentences and parse trees. We extracted syntactic patterns associated with drug-SE pairs from the resulting set of parse trees. We developed pattern-ranking algorithms to prioritize drug-SE-specific patterns. We then selected a set of patterns with both high precisions and recalls in order to extract drug-SE pairs from the entire MEDLINE. In total, we extracted 38,871 drug-SE pairs from MEDLINE using the learned patterns, the majority of which have not been captured in FDA drug labels to date. On average, our knowledge-driven pattern-learning approach in extracting drug-SE pairs from MEDLINE has achieved a precision of 0.833, a recall of 0.407, and an F1 of 0.545. We compared our approach to a support vector machine (SVM)-based machine learning and a co-occurrence statistics-based approach. We show that the pattern-learning approach is largely complementary to the SVM- and co-occurrence-based approaches with significantly higher precision and F1 but lower recall. We demonstrated by correlation analysis that the extracted drug side effects correlate positively with both drug targets, metabolism, and indications. PMID:24928448

Xu, Rong; Wang, QuanQiu

2014-10-01

432

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

433

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

434

Simple Model for Testing Drugs against Nonreplicating Mycobacterium tuberculosis? †  

PubMed Central

Nonreplicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against nongrowing cells that exploits the 18b strain of M. tuberculosis, a streptomycin (STR)-dependent mutant. Optimal conditions were established that allowed 18b cells to replicate in the presence of STR and to survive, but not multiply, following withdrawal of STR. In the presence of the antibiotic, M. tuberculosis 18b was susceptible to the currently approved TB drugs, isoniazid (INH) and rifampin (RIF), and to the experimental drugs TMC207, PA-824, meropenem (MER), benzothiazinone (BTZ), and moxifloxacin (MOXI). After STR depletion, the strain displayed greatly reduced susceptibility to the cell wall inhibitors INH and BTZ but showed increased susceptibility to RIF and PA-824, while MOXI and MER appeared equipotent under both conditions. The same potency ranking was found against nonreplicating M. tuberculosis 18b after in vivo treatment of chronically infected mice with five of these drugs. Despite the growth arrest, strain 18b retains significant metabolic activity in vitro, remaining positive in the resazurin reduction assay. Upon adaption to a 96-well format, this assay was shown to be suitable for high-throughput screening with strain 18b to find new inhibitors of dormant M. tuberculosis. PMID:20679505

Sala, Claudia; Dhar, Neeraj; Hartkoorn, Ruben C.; Zhang, Ming; Ha, Young Hwan; Schneider, Patricia; Cole, Stewart T.

2010-01-01

435

Personality, Drug Preference, Drug Use, and Drug Availability  

ERIC Educational Resources Information Center

This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

2011-01-01

436

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.

437

Acculturation, Cultivation, and Daytime TV Talk Shows  

Microsoft Academic Search

This study explored the cultivation phenomenon among international college students in the United States by examining the connection between levels of acculturation, daytime TV talk show viewing, and beliefs about social reality. It was expected that international students who were heavy viewers of daytime TV talk shows and who scored low on a measure of acculturation about the United States

Hyung-Jin Woo; Joseph R. Dominick

2003-01-01

438

2015 4-H State Food Show Guidelines  

E-print Network

1 2015 4-H State Food Show Guidelines Bringing Texas to the Table Educational programs of the Texas A&M AgriLife Extension Service are open to all people without regard to race, color, sex, religion.D. Shawnte Clawson, MS Subject: 2015 4-H State Food Show Guidelines Being transmitted to you this year via e

439

Serving Up Activities for TV Cooking Shows.  

ERIC Educational Resources Information Center

This paper documents a presentation given on the use of English-language television cooking shows in English-as-a-Second-Language (ESL) and English-as-a-Foreign-Language (EFL) classrooms in Taiwan. Such shows can be ideal for classroom use, since they have a predictable structure consisting of short segments, are of interest to most students,…

Katchen, Johanna E.

440

Exploring visitor experiences at trade shows  

Microsoft Academic Search

Purpose – The purpose of this paper is to investigate business visitor behaviour at trade shows and to propose a complementary view based on the experiential perspective in marketing. Design\\/methodology\\/approach – The paper reports an ethnographic study conducted in the context of ten international trade shows in the textile-apparel industry in Europe. Findings – The study sheds light on the

Diego Rinallo; Stefania Borghini; Francesca Golfetto

2010-01-01

441

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

442

Virtual game show host — Dr. Chestr  

Microsoft Academic Search

This paper describes the design, implementation and evaluation of an interactive virtual human Dr. Chestr: Computerized Host Encouraging Students to Review. Game show hosts exert a unique personality that becomes the trademark of their respective game shows. Our aim is to create virtual humans that can interact naturally and spontaneously using speech, emotions and gesture. Dr. Chestr is our virtual

Raghavi Sakpal; Dale-Marie Wilson

2011-01-01

443

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

444

Relating drug-protein interaction network with drug side effects  

PubMed Central

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Veronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

445

Positive mood broadens visual attention to positive stimuli  

PubMed Central

In an attempt to investigate the impact of positive emotions on visual attention within the context of Fredrickson's (1998) broaden-and-build model, eye tracking was used in two studies to measure visual attentional preferences of college students (n=58, n=26) to emotional pictures. Half of each sample experienced induced positive mood immediately before viewing slides of three similarly-valenced images, in varying central-peripheral arrays. Attentional breadth was determined by measuring the percentage viewing time to peripheral images as well as by the number of visual saccades participants made per slide. Consistent with Fredrickson's theory, the first study showed that individuals induced into positive mood fixated more on peripheral stimuli than did control participants; however, this only held true for highly-valenced positive stimuli. Participants under induced positive mood also made more frequent saccades for slides of neutral and positive valence. A second study showed that these effects were not simply due to differences in emotional arousal between stimuli. Selective attentional broadening to positive stimuli may act both to facilitate later building of resources as well as to maintain current positive affective states. PMID:20431711

Wadlinger, Heather A.; Isaacowitz, Derek M.

2010-01-01

446

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

447

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

448

Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates.  

PubMed

Antibody drug conjugates (ADCs) are a therapeutic class offering promise for cancer therapy. The attachment of cytotoxic drugs to antibodies can result in an effective therapy with better safety potential than nontargeted cytotoxics. To understand the role of conjugation site, we developed an enzymatic method for site-specific antibody drug conjugation using microbial transglutaminase. This allowed us to attach diverse compounds at multiple positions and investigate how the site influences stability, toxicity, and efficacy. We show that the conjugation site has significant impact on ADC stability and pharmacokinetics in a species-dependent manner. These differences can be directly attributed to the position of the linkage rather than the chemical instability, as was observed with a maleimide linkage. With this method, it is possible to produce homogeneous ADCs and tune their properties to maximize the therapeutic window. PMID:23438745

Strop, Pavel; Liu, Shu-Hui; Dorywalska, Magdalena; Delaria, Kathy; Dushin, Russell G; Tran, Thomas-Toan; Ho, Wei-Hsien; Farias, Santiago; Casas, Meritxell Galindo; Abdiche, Yasmina; Zhou, Dahui; Chandrasekaran, Ramalakshmi; Samain, Caroline; Loo, Carole; Rossi, Andrea; Rickert, Mathias; Krimm, Stellanie; Wong, Teresa; Chin, Sherman Michael; Yu, Jessica; Dilley, Jeanette; Chaparro-Riggers, Javier; Filzen, Gary F; O'Donnell, Christopher J; Wang, Fang; Myers, Jeremy S; Pons, Jaume; Shelton, David L; Rajpal, Arvind

2013-02-21

449

Effects of Drug Abuse  

MedlinePLUS

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

450

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.

451

Alcoholism Damages Brain's White Matter, Scans Show  

MedlinePLUS

... Brain's White Matter, Scans Show Areas tied to decision-making, such as how much to drink, seem most ... part of the brain mediates inhibitory control and decision-making, so tragically, it appears that some of the ...

452

GOES Satellite Data Shows Tornado Development  

NASA Video Gallery

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

453

TRMM Satellite Shows Heavy Rainfall in Cristina  

NASA Video Gallery

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

454

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

NASA Astrophysics Data System (ADS)

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