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Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...

Science.gov (United States)

Magnetic drug targeting, using core-shell magnetic carrier particles loaded with anti-cancer drugs, is an emerging and significant method of cancer treatment. Gold shell-iron core nanoparticles (Fe@Au) were synthesized by the reverse micelle method with aqueous reactants, surfactant, co-surfactant and oil phase. XRD, XPS, TEM and magnetic property measurements were utilized to characterize these core-shell nanoparticles. Magnetic measurements showed that the particles were superparamagnetic at room temperature and that the saturation magnetization decreased with increasing gold concentration. The anti-cancer drug doxorubicin (DOX) was loaded onto these Fe@Au nanoparticle carriers and the drug release profiles showed that upto 25% of adsorbed drug was released in 80 h. It was found that the amine (-NH2) group of DOX binds to the gold shell. An in vitro apparatus ...

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The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with non-classical cellular targets. Unfortunately, target-based drug discovery against...Full Text Available

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Magnetic particles have become very promising materials for drug delivery. However, preparation of magnetite particles with high surface area, biocompatibility, strong magnetic response, and suitable particle size still remains a major challenge. In this report, magnetite nanocrystal clusters with high surface areas were fabricated through a solvothermal process by introducing ammonium acetate as a porogen and trisodium citrate as a surface modification agent. The porosity, which was controlled by the reactant concentration, has been investigated in detail. The surface area of the nanocrystal clusters was as high as 141?m(2) g(-1) . Ibuprofen, as a model drug, was entrapped into the magnetite carriers. The interfacial interaction between the carboxylic groups on the drug molecules and the carboxylate groups on the carriers enhanced the loading efficiency. Low cytotoxicity in MCF-7 cell and in vitro constant ...

International Nuclear Information System (INIS)

The long and resource intensive process of drug discovery and development is confronted with the basic challenge of providing effective and safe therapies at reasonably low costs. The better the mechanism of a disease is known, the higher the probability to find an appropriate therapy. Also, the better and earlier a disease can be diagnosed and characterized, the higher the chance to be able to interfere in this process with a chemical entity. This reasoning sets the framework for the use of imaging in drug discovery. We discuss the relevance of magnetic resonance imaging and spectroscopy to derive anatomical, functional, metabolic and target-related information in the context of pharmacological research in vivo. (author)

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Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug-delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundGene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drug targets....Full Text Available

UK PubMed Central (United Kingdom)

Essential in mitosis, the human Kinesin-5 protein is a target for >80 classes of allosteric compounds that bind to a surface-exposed site formed by the L5 loop. Not established is why there...Full Text Available

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Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracel...

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A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

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The present work gives preliminary results of analysis of drug mixtures (NEPHROSAL tea bag) and its water infusion. In a sample of dried drugs the elements K, Ca, Mn, Fe, Ni, Cu, Zn, Br, Rb, Sr, Pb were identified, whereas in their water infusion only Ca, Mn, Zn and Sr were found. The method applied was radionuclide X-ray fluorescence analysis using a radionuclide source "1"0"9Cd, a Si/Li semiconductor detector and a multichannel analyzer Canberra 8100. (author) 6 refs.; 3 figs.

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A novel drug delivery system for the treatment of brain tumors was formulated by methotrexate (MTX)-loaded polymeric nanoparticles (NPs) based on Glycol chitosan (GCS) and Dextran sulfate (DS). The physicochemical properties of resulting particles were investigated, evidencing the contribution of these nanoparticles for brain targeting. In vitro release of MTX was also evaluated. The GCS-DS nanoparticles have been developed based on the modulation of ratio show promise as a system for controlled delivery of the drug to the brain. PMID:21782844

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Abstract Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis o...

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Isolation of functional and intact mitochondria from solid tissue is crucial for studies that focus on the elucidation of normal mitochondrial physiology and/or mitochondrial dysfunction in conditions such as aging, diabetes, and cancer. There is growing recognition of the importance of mitochondria both as targets for drug development and as off-target mediators of drug side effects. Unfortunately, mitochondrial isolation from tissue is generally carried out using homogenizer-based methods that require extensive operator experience to obtain reproducible high-quality preparations. These methods limit dissemination, impede scale-up, and contribute to difficulties in reproducing experimental results over time and across laboratories. Here we describe semiautomated methods to disrupt tissue ...

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Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput screen for identification of inhibitors of a human intestinal CaCC based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells after lentiviral infection with the yellow fluorescent halide-sensing protein YFP-H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2-aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to multiple calcium-elevating agonists, including thapsigargin, without inhibition of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis transmembrane conductance regulator chloride channels. These compounds also inhibited ...

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While there is growing interest in Real Time Pricing as a competitive tool, its adoption to date has been constrained by wariness on the part of many utilities and many of their customers. That wariness is not misplaced, for Real Time Pricing is not for everyone. In order for both utilities and their customers to benefit, the pricing system must be properly tailored for, and offered to, the appropriate audience. This paper discusses needs for identifying targets, implications of targeting of Real Time Pricing to various types of customers, and implications for design and marketing of such pricing systems. Examples from utility experiences are provided, and recommendations are offered for development of improved targeting of Real Time Pricing.

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9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 ?mg/kg/day to CD? rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglo...

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Loss of the sense of smell can be easily confirmed in any physician's office by having the patient try to identify various odors. The etiology of anosmia can be extremely varied, including nasopharyngeal disorders such as rhinitis and tumors; neurologic conditions such as head trauma, neoplasms, vascular lesions and infections of the central nervous system; viral infections; familial and congenital disorders; drugs; industrial exposure; endocrine diseases, and several other disorders. The prognosis of anosmia is guarded, and its treatment depends on the etiology.

International Nuclear Information System (INIS)

Target materials for inertial fusion energy (IFE) power plant designs might be selected for a wide variety of reasons including wall absorption of driver energy, material opacity, cost and ease of fabrication. While each of these issues are of great importance, target materials should also be selected based upon their safety and environmental (S and E) characteristics. The present work focuses on the recycling, waste management and accident dose characteristics of potential target materials. If target materials are recycled so that the quantity is small, isotopic separation may be economically viable. Therefore, calculations have been completed for all stable isotopes for all elements from lithium to polonium. The results of these calculations are used to identify specific isotopes and elements that are most likely to be offensive as well as those most likely to be acceptable in ...

UK PubMed Central (United Kingdom)

A goal of our research is to identify biochemical factors that underlie the susceptibility of bone marrow cell populations to benzene metabolites so as to develop a mechanistically based chemoprotective...Full Text Available

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Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...

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The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.

UK PubMed Central (United Kingdom)

Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic...Full Text Available

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A recently developed neutron diagnostic probe system has the potential to satisfy a significant number of van-mobile and fixed- portal requirements for nondestructive verification of sealed munitions and detection of contraband explosives and drugs. The probe is based on a unique associated-particle sealed-tube neutron generator (APSTNG) that interrogates the object of interest with a low-intensity beam of 14-MeV neutrons generated from the deuterium-tritium reaction and that detects the alpha-particle associated with each neutron. Gamma-ray spectra of resulting neutron inelastic scattering and fission reactions identify nuclides associated with all major chemicals in chemical warfare agents, explosives, and drugs, as well as many pollutants and fissile and fertile special nuclear material. Flight times determined from determined from detection times of the gamma-rays and alpha-particles yield a separate tomographic image ...

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Background Identifying susceptibility genes for endophenotypes by studying analogous behaviors across species is an important strategy for understanding the pathophysiology underlying psychiatric disorders. This approach provides novel biological pathways plus validated animal models critical for selective drug development. One such endophenotype is avoidance behavior. Methods In the present study, novel automated registration methods for longitudinal behavioral assessment in home cages are used to screen a panel of recently generated mouse chromosome substitution strains that are very powerful in quantitative trait loci (QTL) detection of complex traits. In this way, we identified chromosomes regulating avoidance behavior (increased sheltering preference) independent of motor activity lev...

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Background: Determinants of warfarin use and anticoagulation levels in atrial fibrillation (AF) patients have not been clarified thoroughly. Methods and Results: A total of 6,324 patients with non-valvular AF and congestive heart failure, hypertension, age, diabetes, prior stroke (CHADS(2)) score ?1 were used to investigate determinants of warfarin use, and 6,932 patients with AF receiving warfarin were used to investigate determinants of international normalized ratio (INR) of prothrombin time. Target INR levels for non-valvular AF patients were 1.6-2.6 for patients aged ?70 years and 2-3 for patients aged transient ischemic attack (TIA), and had higher CHADS(2) scores than those not receiving warfarin. Determinants of warfarin use were age (?60 years), AF type (persistent and permanent), and comorbidities (congestive heart failure, diabetes mellitus, and prior stroke or TIA). Use of antiplatelet drugs was a negative determinant of warfarin ...

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PMID:20636852

UK PubMed Central (United Kingdom)

There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density...Full Text Available

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... Accession Number : ADA518761. Title : Whatever Happened to the "War on Drugs"? Descriptive Note : Journal article. Corporate ...

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Abstract:- Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn-s disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn-s disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and t...

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The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation...

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Nano-sized silica is a promising material for disease diagnosis, cosmetics and drugs. For the successful application of nano-sized material in bioscience, evaluation of nano-sized material toxicity is important. We previously found that nano-sized silica particles with a diameter of 70nm showed acute liver failure in mice. Here, we performed histological analysis of major organs such as the liver, spleen, lung, kidney, brain and heart in mice, chronically injected with 70-nm silica particles for 4weeks. Histological analysis revealed hepatic microgranulation and splenic megakaryocyte accumulation in these 70-nm silica particles treated mice, while the kidney, lung, brain and heart remained unaffected. Thus, liver and spleen appear to be the major target organs for toxicity by the chronic a...

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The Network for a Healthy California (Network) employs a Geographic Information System (GIS) to identify the target audience and plan program activities because GIS is a powerful tool for assisting in data integration and planning. This paper describes common uses of GIS by Network contractors as well as demonstrating the possibilities of GIS as a useful tool for public health programs and audience targeting in general. Narrative examples supported with graphics describe how 1) Network contractors use the GIS to identify eligible census tracts to carry out their work, 2) the GIS can map neighborhood assets in eligible census tracts throughout California, 3) the GIS can map health behavior data to the county level throughout California, and 4) the GIS can map selected indicators of healthy ...

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TiH{sub 2} and TiD{sub 2} thick targets were bombarded with 100 to 200 keV protons. Evidence for nuclear reactions was obtained by means of a surface barrier particle detector. Proton irradiation of TiD{sub 2} produced the following observations: {alpha} particle emission identified as (p, {alpha}) reactions from {sup 11}B and {sup 7}Li impurities in the target at ppm concentrations; and {approx}3 MeV proton and {approx}1 MeV triton emission from secondary D-D reactions caused by elastic scattering of the primary proton with a target deuteron. A 3.9 MeV {alpha} particle peak measured by others was not observed. (author)

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Target recognition requires the ability to distinguish targets from non-targets, a capability called one-class generalization. Many neural network pattern classifiers fail as one-class classifiers because they use open decision boundaries. To function as one-class classifier, a neural network must have three types of generalization: within-class, between-class, and out-of-class. We discuss these three types of generalization and identify neural network architectures that meet these requirements. We have applied our one-class classifier ideas to the problem of automatic target recognition in synthetic aperture radar. We have compared three neural network algorithms: Carpenter and Grossberg`s algorithmic version of the Adaptive Resonance Theory (ART-2A), Kohonen`s Learning Vector Quantization (LVQ), and Reilly and Cooper`s Restricted Coulomb Energy network (RCE). The ART 2-A neural ...

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BACKGROUND AND PURPOSE Human K2P3.1 (TASK1) channels represent potential targets for pharmacological management of atrial fibrillation. K2P channels control excitability by stabilizing membrane potential and by expediting repolarization. In the heart, inhibition of K2P currents by class III antiarrhythmic drugs results in action potential prolongation and suppression of electrical automaticity. Carvedilol exerts antiarrhythmic activity and suppresses atrial fibrillation following cardiac surgery or cardioversion. The objective of this study was to investigate acute effects of carvedilol on human K2P3.1 (hK2P3.1) channels. EXPERIMENTAL APPROACH Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record hK2P3.1 currents from Xenopus oocytes, Chinese hamster o...

UK PubMed Central (United Kingdom)

The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available

UK PubMed Central (United Kingdom)

Leukocyte infiltration across an activated brain endothelium contributes to the neuroinflammation seen in many neurological disorders. Recent evidence shows that IL-17-producing T-lymphocytes (e.g.,...Full Text Available

UK PubMed Central (United Kingdom)

To understand how DEXD/H-box proteins recognize and interact with their cellular substrates, we have been studying Prp28p, a DEXD/H-box splicing factor required for switching the U1 snRNP with the U6...Full Text Available

International Nuclear Information System (INIS)

As part of the Nondestructive Evaluation Reliability Program sponsored by the US Nuclear Regulatory Commission, the Pacific Northwest Laboratory is developing a method that uses risk-based approaches to establish in-service inspection plans for nuclear power plant components. This method uses probabilistic risk assessment (PRA) results and Failure Modes and Effects Analysis (FEMA) techniques to identify and prioritize the most risk-important systems and components for inspection. The Surry Nuclear Power Station Unit 1 was selected for pilot applications of this method. The specific systems addressed in this report are the reactor pressure vessel, the reactor coolant, the low-pressure injection, and the auxiliary feedwater. The results provide a risk-based ranking of components within these systems and relate the target risk to target failure probability values for individual components. These results will be used to guide ...

UK PubMed Central (United Kingdom)

Nearly every drug may cause changes to ocular tissues through a variety of mechanisms. Medication overdoses, drug–drug interactions but also chronic administration of medications at...Full Text Available

UK PubMed Central (United Kingdom)

The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to...Full Text Available

International Nuclear Information System (INIS)

The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could ...

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The influence of headspace solid-phase microextraction (HS-SPME) variables, namely, sample concentration, salt concentration and sample amount, on the equilibrium headspace analysis of the main volatile flavor compounds released from soursop was investigated. A total of 35 volatile compounds, comprising 19 esters, six alcohols, three terpenes, two acids, two aromatics, two ketones and an aldehyde, were identified. The results indicated that all response-surface models were significantly (p<0.05) fitted for 10 target volatile flavor compounds. The results further indicated that more than 65% of the variation in the equilibrium headspace concentrations of target volatile flavor compounds could be explained by the final reduced models, with high R2 values ranging from 0.658 to 0.944. Multiple...

UK PubMed Central (United Kingdom)

BackgroundNonsteroidal anti-inflammatory drugs are commonly used to treat postoperative and chronic pain. Animal studies suggest these drugs act in part by blocking...Full Text Available

UK PubMed Central (United Kingdom)

In rats, drug-induced depression of the central nervous system has been shown generally to be associated with an elevation in level of total acetylcholine in the brain. This generalization held true...Full Text Available

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Anticancer drug thyotepa (10 mg/ kg) hormonal compound thyroxine (40 mg / kg) and D3 vitamin (30,000 IU / kg) have been administrated simply or associated to Wistar rats bearing Walker carcinosarcoma. The chromatin (the complex of DNA and proteins from nuclei) has been extracted from Walker tumor and submitted to fast neutron beams produced by deuterons (13 MeV) on thick Be target at an IPNE U-120 Cyclotron, in doses of 5-100 Gy. Thermal transition of chromatin fluorescence intensity of chromatin-ethidium bromide complexes and intrinsic fluorescence of chromatin have been analysed. Association of thiotepa with thyroxine and D3 vitamin produced a diminution of chromatin lesions induced by the cytostatic. Thus in the effects of fast neutrons radiolysis in chromatin significant differences occurred. These results could help to improve the methodology of associated chemotherapy-radiotherapy in clinical applications. (author).

International Nuclear Information System (INIS)

Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional ...

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There is a need for earlier and more accurate cancer diagnostics as well as new targets for cancer immunotherapy. To this end, it is important to identify sets of tumour antigens specific for different cancer forms. Several methods that identify potential tumour antigens in an arrayed and high-throughput format have been developed during the last years of SEREX (serological identification of antigens by recombinant expression cloning) related research. Such techniques may hold the potential to describe the complete immunogenic part of the cancer proteome, also called the cancer immunoproteome.We have developed a powerful platform for automated serological high-throughput filter screening of tumour cDNA libraries. The screening format of this method is 18,000 single cDNAs clones, which is s...

Science.gov (United States)

ABSTRACT: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor ?/? (PPAR?/?) and PPAR?. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.See related research article: http://genomebiology.com/2011/12/8/R75. PMID:21861850

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With the exception of Sand Springs in Williamstown, Massachusetts, there are no identifiable hydrothermal geothermal resources in the New England region. The radioactive plutons of the White Mountains of New Hampshire do not, apparently, contain sufficient stored heat to make them a feasible target for an induced hydrothermal system such as exists at Fenton Hill near Los Alamos, New Mexico. The only potential source of low grade heat is the large volume of ground water contained within the unconsolidated sediments related to the Pleistocene glaciation of the region. During the course of the survey an unusual and unexplained thermal anomaly was discovered in St. Johnsbury, Vermont, which is described.

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The mass deployment of electric and plug-in hybrid electric vehicles (EVs and PHEVs) that rely on low greenhouse gas (GHG) emission electricity generation has great potential to significantly reduce the consumption of petroleum and other high CO2-emitting transportation fuels. The vision of the Electric and Plug-in Hybrid (EV/PHEV) Vehicles Roadmap is to achieve by 2050 the widespread adoption and use of EVs and PHEVs, which together represent more than 50% of annual LDV (light duty vehicle) sales worldwide. In addition to establishing a vision, this roadmap sets strategic goals to achieve it, and identifies the steps that need to be taken to accomplish these goals. This roadmap also outlines the roles and collaboration opportunities for different stakeholders and shows how government policy can support the overall achievement of the vision. The strategic goals for attaining the widespread adoption and use of EVs and PHEVs worldwide by 2050 cover the development of ...

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... The anti-tumor drugs used for these studies were: busulfan, cyclophosphamide, metho- trexate, vinblastine and 6-mercaptopurine. ...

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Control of human filarial infections currently depends on chemotherapeutic strategies predominantly directed at microfilariae. Doxycycline therapy in an extended daily dose regimen sterilizes and kills adult stages, but the utility of this drug for routine field use remains an issue of concern. No macrofilaricidal drugs with efficacy after one or two doses are available for use, delaying the achievement of the elimination or eradication of onchocerciasis and lymphatic filariasis. Moxidectin, a macrocyclic lactone, is currently in clinical trials for onchocerciasis. A few other drugs that have already been approved for use in veterinary practice or in human medicine for other indications are available for investigation. Early drug discovery pipelines are poorly populated and the process of ...

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Signal-to-noise-ratio (SNR) thresholds for microarray data analysis were experimentally determined with an oligonucleotide array that contained perfect match (PM) and mismatch (MM) probes based upon four genes from Shewanella oneidensis MR-1. A new SNR calculation, called signal to both standard deviations ratio (SSDR) was developed, and evaluated along with other two methods, signal to standard deviation ratio (SSR), and signal to background ratio (SBR). At a low stringency, the thresholds of SSR, SBR, and SSDR were 2.5, 1.60 and 0.80 with oligonucleotide and PCR amplicon as target templates, and 2.0, 1.60 and 0.70 with genomic DNA as target templates. Slightly higher thresholds were obtained at the high stringency condition. The thresholds of SSR and SSDR decreased with an increase in the complexity of targets (e.g., target types), and the presence of background DNA, and a decrease in the composition ...

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Constraints on target chamber first wall and target designs that will enable NIF debris shields to survive

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Trace elemental analysis was carried out in various parts of some anti-diabetic medicinal plants using PIXE technique. A 3 MeV proton beam was used to excite the samples. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Br, Rb and Sr were identified and their concentrations were estimated. The results of the present study provide justification for the usage of these medicinal plants in the treatment of diabetes mellitus (DM) since they are found to contain appreciable amounts of the elements K, Ca, Cr, Mn, Cu, and Zn, which are responsible for potentiating insulin action. Our results show that the analyzed medicinal plants can be considered as potential sources for providing a reasonable amount of the required elements other than diet to the patients of DM. Moreover, these results can be used to set new standards for prescribing the dosage of the herbal drugs prepared from these plant materials.

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The identification of genes influencing sensitivity to stimulants and opioids is important for determining their mechanism of action and may provide fundamental insights into the genetics of drug abuse. We used a panel of C57BL/6J (B6; recipient)x A/J (donor) chromosome substitution strains (CSSs) to identify quantitative trait loci (QTL) for both open field activity and sensitivity to the locomotor stimulant response to methamphetamine (MA). Mice were injected with saline (days 1 and 2) and MA (day 3; 2 mg/kg i.p.). We analyzed the total distance traveled in the open field for 30 min following each injection. CSS-8, -11 and -16 showed reduced MA-induced locomotor activity relative to B6, whereas CSS-10 and -12 showed increased MA-induced locomotor activity. Further analysis focused on CSS...

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This guide is one of the actions following from the recommendations of the Thermie B project that aimed to support the development of a new European Integrated Clean Coal (CCT) Program concept (STR - 1121 - 96), November 1998. The concept aimed to enhance the market deployment of EU CCTs. This guide is prepared for EU industry to help them finding support for their CCT exports to the target markets. The guide will include easy accessible information on the most relevant EC-programs and is intended as a practical tool for EU CCT industry, to assist them in identifying and selecting the export support and programs best able to support their specific export assistance. The guide is a manual (signpost) through the 'jungle of assistance' and therefore does not include extensive information on application procedures, since this kind of information can be easily obtained, once the relevant program is identified. ...

International Nuclear Information System (INIS)

In the framework of spallation neutron sources and accelerator-driven systems, the international PISA (Proton-induced Spallation) collaboration has initiated measurements of total- and double-differential cross-sections for products of spallation reactions in a wide range of target nuclei (GU) at the COSY proton accelerator in Julich (Germany). The purpose is to study secondary particle production created in structural, window and target materials via proton beams up to 2.5 GeV of incident kinetic energy. Residual nuclei [H, He up to intermediate mass fragment (IMF)] production cross-sections are of great importance for estimating the damage to target and structure materials involving the planned spallation neutron sources, given that the lifetime of window and target materials is directly associated to those cross-sections. The demand for reliable theoretical predictions on production cross-sections is ...

International Nuclear Information System (INIS)

A critical issues study of a symmetric illumination, direct drive laser fusion reactor called SIRIUS has been conducted. In particular, the uniformity requirements for direct drive targets have been assessed and it is shown that respectable gains (more than 60) could be obtained at modest (2MJ) KrF laser energies. Previous ICF cavity designs have been examined for use in a symmetric illumination geometry and features from several designs have been combined into a dry wall cavity design with a radius of 8 meters. Neutronic and photonic analysis shows that the present SIRIUS cavity design can breed sufficient tritium (breeding ratio = 1.17) even with 32 laser ports penetrating the cavity. However, it was found that there are a few critical issues that remain to be solved before a self-consistent reactor design could be initiated. Radiation damage to final optics, thermal performance of SiC tiles on the SIRIUS cavity wall, and performance of direct drive ...

UK PubMed Central (United Kingdom)

HIV-1 nonsubtype B variants account for the majority of HIV infections worldwide. Drug resistance in individuals who have never undergone antiretroviral therapy can lead to early failure and...Full Text Available

UK PubMed Central (United Kingdom)

Sponges can provide potential drugs against many major world-wide occurring diseases. Despite the high potential of sponge derived drugs no sustainable production method has been developed. Thus far...Full Text Available

Medline Plus

... HIV & AIDS (15) I Infectious Diseases (22) Injection Drug Use (7) M Mental Illness (141) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (117) Inhalants (13) K Ketamine (1) L LSD ( ...

Medline Plus

... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (138) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (116) Inhalants (12) K Ketamine (1) L LSD ( ...

UK PubMed Central (United Kingdom)

Multidrug-resistant tuberculosis is an increasing public health concern in many parts of the world, especially in low-income countries, where most cases occur. Traditional drug susceptibility testing...Full Text Available

UK PubMed Central (United Kingdom)

OBJECTIVES:To investigate the prevalence of potential drug interactions at the intensive care unit of a university hospital in Brazil and to analyze their clinical significance.METHODS:This...Full Text Available

UK PubMed Central (United Kingdom)

The evolution of drug resistant bacteria is a severe public health problem, both in hospitals and in the community. Currently, some countries aim at concentrating highly specialized services in large...Full Text Available

UK PubMed Central (United Kingdom)

Purpose of reviewPhysicians, researchers and policy makers must understand the myriad consequences of multidrug and extensively drug-resistant tuberculosis (TB) within...Full Text Available

UK PubMed Central (United Kingdom)

The purpose of this study was to illuminate the experiences of poor, urban HIV-positive drug users. Sixty participants were asked about HIV risk behaviors, the impact of HIV on their lives,...Full Text Available

UK PubMed Central (United Kingdom)

Serum specimens obtained from a nationwide sample of parenteral drug abusers (PDAs) during the period 1971-72 had previously been screened for human immunodeficiency virus (HIV) antibodies. Some specimens...Full Text Available

UK PubMed Central (United Kingdom)

The drug-binding properties of human alpha-foetoprotein (alpha FP) were investigated by a fluorescence-spectral method. Human alpha FP was shown to bind to albumin's site I marker (warfarin, phenylbutazone),...Full Text Available

UK PubMed Central (United Kingdom)

Current methods for drug susceptibility testing of Mycobacterium tuberculosis are either costly or slow. As the prevalence of multidrug-resistant strains increases, the need for fast,...Full Text Available

UK PubMed Central (United Kingdom)

The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available

UK PubMed Central (United Kingdom)

This joint statement was developed by the CMA and the Canadian Pharmaceutical Association, a national association of pharmacists, and includes the goal of drug therapy, strategies for collaboration...Full Text Available

Science.gov (United States)

...treated for leukemia. B' s physician, who is employed by the HMO, is considering a treatment plan that includes six-mercaptopurine, a drug for treating leukemia in most children. However, the drug could be fatal if taken by a small percentage of...

DEFF Research Database (Denmark)

Udgivelsesdato: 2005-Mar

British Library Electronic Table of Contents (United Kingdom)

Schools have increasingly been targeted as appropriate sites for mental health promotion and teachers are considered well placed to identify issues concerning students' social and emotional well-being. Whilst teachers are now expected to be responsive to a wide range of student needs and circumstances, they receive little in their pre-service and subsequent teacher education to adequately prepare them for such realities. This paper reports the findings of a study that investigated teacher perspectives on student mental health and mental health education, including their sense of self-efficacy in relation to promoting and supporting children's mental well-being in schools. These findings highlight a complex interplay between teachers' constructions of 'mental health', the importance they pl...

International Nuclear Information System (INIS)

The neutron-rich Mn isotopes from A=59 to 63 have been studied through multi-nucleon transfer reactions by bombarding a "2"3"8U target with a beam of "7"0Zn at an energy of E_l_a_b=460 MeV. Prompt #gamma# rays measured by the CLARA array have been identified unambiguously for each nucleus, using coincidence relationships with ions detected in the high-acceptance magnetic spectrometer PRISMA. The new data extends the knowledge of the low-lying level structure of Mn isotopes, which is discussed in terms of the systematics of the region. Results are compared with large-scale shell-model calculations using different effective interactions and valence spaces.

British Library Electronic Table of Contents (United Kingdom)

Coumarin (1,2-benzopyrone) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in humans by simulating both routes of exposure. The concentration-time profile in liver revealed a higher peak concentration (Cmax-hep) for the oral when compared to the dermal route. The area under the concentration-time curve in the liver (AUChep) was found the same for both routes if the same extent of absorption is assumed. Dose response information from published rat studies were used to identify the metric relevant for liver toxicity. Liver exposure levels resulting from doses and durations as outlined in the studies were simulated in a rat model. We obtained 31 data pair...

Energy Technology Data Exchange (ETDEWEB)

We have measured production cross-sections of the new neutron-rich isotopes {sup 58}Ti, {sup 61}V, {sup 63}Cr, {sup 66}Mn, {sup 69}Fe, {sup 71}Co and neighbouring isotopes that have been identified as projectile fragments from reactions between a 500 MeV/u {sup 86}Kr beam and a beryllium target. The isotope identification was performed with the zero-degree magnetic spectrometer FRS at GSI, using in addition time-of-flight and energy-loss mesurements. The experimental production cross-sections for the new nuclides and neighbouring isotopes are compared with an empirical parameterization. The resulting prospects for reaching even more neutron-rich isotopes, such as the doubly-magic nuclide {sup 78}Ni, are discussed. (orig.).

International Nuclear Information System (INIS)

We have measured production cross-sections of the new neutron-rich isotopes "5"8Ti, "6"1V, "6"3Cr, "6"6Mn, "6"9Fe, "7"1Co and neighbouring isotopes that have been identified as projectile fragments from reactions between a 500 MeV/u "8"6Kr beam and a beryllium target. The isotope identification was performed with the zero-degree magnetic spectrometer FRS at GSI, using in addition time-of-flight and energy-loss measurements. The experimental production cross-sections for the new nuclides and neighbouring isotopes are compared with an empirical parametrization. The resulting prospects for reaching even more neutronrich isotopes, such as the doubly-magic nuclide "7"8Ni, are discussed. (orig.).

British Library Electronic Table of Contents (United Kingdom)

Background In chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid metabolism of protostomes, such as Drosophila melanogaster. Methods Drosophila genome was searched for genes encoding proteins with ?50% identity to human retinol dehydrogenase 12 (RDH12). The corresponding proteins were expressed in Sf9 cells and biochemically characterized. Their phylogenetic relationships were analyzed using PHYLIP software. Results A total of six Drosophila SDR genes were identified. Five of these genes are clustered on chromosome 2 and one is located on chromosome X. The deduced proteins are 300 to 406 amino acids long and are associated with microsomal membranes. They recognize all-trans-retinaldehyd...

British Library Electronic Table of Contents (United Kingdom)

Objective: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. Methods: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage,...

Energy Technology Data Exchange (ETDEWEB)

The publication presents an outline of the subject of energy management and attempts to test the hypotheses that targeted knowledge management may result in new developments and potentials, and if these are at all desirable. On this basis, a knowledge management system will be developed that may effectively promote developments and potentials in the field of energy management. The tools and fundamentals of energy management are looked into, and the given situation and desired goals are identified by means of an enquiry. This is a scientific study that aims at providing empirical information on the situation and views on the subject of energy management. The analysis, which is supported by an enquiry sheet, is to provide a basis for testing the assumed hypothesis. Further, the potential acceptance and utilization potential of decisive knowledge management in the facility and real estate management sector are to be tested. The energy knowledge ...

British Library Electronic Table of Contents (United Kingdom)

Measurement of serum biochemical parameters in response to metal exposures can be especially useful to help identify target organs of toxicity as well as the general health status of animals. Oreochromis niloticus were exposed to 5.0?mg/L?Zn, 1.0?mg/L?Cd, and 5.0?mg/L?Zn?+?1.0?mg/L?Cd mixture for 7 and 28?days, and alterations in serum enzyme activities and ion levels were measured. Significant changes in all the biochemical parameters were found to be time dependent. Following metal exposure, alkaline phosphatase activity was elevated at both exposure periods. No changes in activities of lactate dehydrogenase and lipase were observed in response to single or combined Zn and Cd exposure at 7?days while they increased at 28?days. Fish exposed to metals showed a decrease in cholinesterase ac...

British Library Electronic Table of Contents (United Kingdom)

The aim of this study was to assess the feasibility of radiosterilization of drugs aqueous solutions and to evaluate the effects of some additives, such as mannitol, nicotinamide and pyridoxine, which might protect the drug from degradation. Metoclopramide was selected as a model drug. The structures of the degradation products were determined to gain insight on the radiolysis mechanisms in aqueous solution in order to design strategies to lower the drug degradation.Metoclopramide hydrochloride aqueous solutions with and without excipients were irradiated either with gamma rays or high-energy electrons. HPLC-DAD was used to measure the loss of chemical potency and to quantify the degradation products which were also characterized by LC-APCI-MS-MS. Metoclopramide recovery for gamma and elec...

Science.gov (United States)

A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n=18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular carcinoma (HCC) and we ...

Science.gov (United States)

Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the ...

International Nuclear Information System (INIS)

Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, ...

Energy Technology Data Exchange (ETDEWEB)

The most serious challenges in the design of chambers for inertial fusion energy (IFE) are 1) protecting the first wall from fusion energy pulses on the order of several hundred megajoules released in the form of x rays, target debris, and high energy neutrons, and 2) operating the chamber at a pulse repetition rate of 5-10 Hz (i.e., re-establishing, the wall protection and chamber conditions needed for beam propagation to the target between pulses). In meeting these challenges, designers have capitalized on the ability to separate the fusion burn physics from the geometry and environment of the fusion chamber. Most recent conceptual designs use gases or flowing liquids inside the chamber. Thin liquid layers of molten salt or metal and low pressure, high-Z gases can protect the first wall from x rays and target debris, while thick liquid layers have the added benefit of protecting structures from fusion neutrons thereby ...

J-STORE (Japan)

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UK PubMed Central (United Kingdom)

All microRNA (miRNA) target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

Threat characterization is a key component in evaluating the threat faced by control systems. Without a thorough understanding of the threat faced by critical infrastructure networks, adequate resources cannot be allocated or directed effectively to the defense of these systems. Traditional methods of threat analysis focus on identifying the capabilities and motivations of a specific attacker, assessing the value the adversary would place on targeted systems, and deploying defenses according to the threat posed by the potential adversary. Too many effective exploits and tools exist and are easily accessible to anyone with access to an Internet connection, minimal technical skills, and a significantly reduced motivational threshold to be able to narrow the field of potential adversaries effectively. Understanding how hackers evaluate new IT security research and incorporate significant new ideas into their own tools provides a means of ...

International Nuclear Information System (INIS)

From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local (plus distant) relapses in 23%. Most of the relapses occurred during the first 3 years of observation. Failure rate was high in patients undergoing irradiation alone (44%). Initial tumour mass (> 100 ml) and histopathologic response to initial chemotherapy were identified as ...

Science.gov (United States)

... drugs, foods, environmental conditions, and behavioral disorders (1,8,10,17,18,24,29). In addition, we designed a self-rated ...

UK PubMed Central (United Kingdom)

Local anesthetics are frequently administered in dentistry and thus can be expected to be a major source of drug-related complications in the dental office. Additionally, the dentist will more often...Full Text Available

UK PubMed Central (United Kingdom)

Standardization of herbal formulations is essential in order to assess the quality of drugs, based on the concentration of their active principles. This article reports on standardization of Ajmodadi...Full Text Available

Medline Plus

Enter Search terms A-Z Index Home Food Drugs Medical Devices Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Radiation-Emitting Products Tobacco ...

British Library Electronic Table of Contents (United Kingdom)

Background/Objectives: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. Methods: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. Results: While BNP values on admission were poorly informative, subsequent BNP measurements (11 +- 6 h after admission) were significantly increased in patients with CS comp...

Science.gov (United States)

uv irradiation (365 nm) of air-saturated methanol solutions of 20 drugs absorbing in the 300 to 400 nm region gave rise to oxygen uptake, as determined with a polarographic oxygen electrode. The drugs were tested for photosensitizing capability by either a Type I (free radical) or a Type II (single molecular oxygen) mechanism. This testing was done by the inclusion of either acrylamide or 2,5-dimethylfuran in the irradiated drug solution, with observation of the subsequent polymerization or oxidation, respectively. Phenothiazine and thiazide derivatives appear capable of photosensitization by both mechanisms; promethazine, trifluoperazine, and furosemide show relatively high reactivity. Diazepam (weak), hexachlorophene, aminacrine, pyrilamine, tetracycline, demeclocyline, quinine, and anthracene (strong) react only by a Type II mechanism, with a photosensitizing efficiency increasing in the order given. A correlation ...

UK PubMed Central (United Kingdom)

The polyene antibiotic Amphotericin B (AMB) is one of the first therapeutic agents to be marketed commercially as nanosized formulations in which the drug is associated with lipids as liposomes or complexes....Full Text Available

UK PubMed Central (United Kingdom)

BACKGROUNDNew diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,...Full Text Available

UK PubMed Central (United Kingdom)

Despite the existence of effective analgesic drugs, many cancer patients live and die with ineffective pain control. The control of cancer pain is largely achievable with the appropriate use of available...Full Text Available

UK PubMed Central (United Kingdom)

A case of intraocular coenurosis was clinically diagnosed and treated with praziquantel. The drug destroyed the coenurus, but vision was lost through toxic endophthalmitis and retinal detachment. There...Full Text Available

UK PubMed Central (United Kingdom)

With the spread of chloroquine resistant Plasmodium falciparum the control of malaria has become increasingly complex. In recent years, particular concern has arisen over how best to prevent malaria...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Gastrointestinal patches represent a novel multiparticulate drug delivery system able to increase the intestinal absorption of drugs with poor bioavailability. The number of patches to administer is a critical issue since it is related to the surface and drug concentration at the absorption site. The objective of this article is to evaluate the effect of the number of administered patches on the final absorption of leuprolide, a peptide chosen as model drug, assuming complete adhesion of all the devices to the intestinal membrane. The same dose of leuprolide was encapsulated into 2, 4 and 6 patches; the resulting intestinal absorption profiles were measured with the Ussing chamber ex vivo experimental setup and compared between them. The results showed that varying the number of patches, t...

UK PubMed Central (United Kingdom)

Carboxylesterases (CE) are ubiquitous enzymes that hydrolyze numerous ester-containing xenobiotics, including complex molecules, such as the anticancer drugs irinotecan (CPT-11) and capecitabine...Full Text Available

Science.gov (United States)

Introduction Uchide and Ide [SSA Spring Meeting, 2009] proposed a new framework for studying the scaling and overall nature of earthquake rupture growth in terms of cumulative moment functions. For better understanding of rupture growth processes, spatiotemporally local processes are also important. The nature of high-frequency (HF) radiation has been investigated for some time, but its role in the earthquake rupture process is still unclear. A wavelet analysis reveals that the HF radiation (e.g., 4 - 32 Hz) of the 2004 Parkfield earthquake is peaky, which implies that the sources of the HF radiation are isolated in space and time. We experiment with applying a matched filter analysis using small template events occurring near the target event rupture area to test whether it can reveal the HF radiation sources for a regular large earthquake. Method We design a matched filter for multiple components and stations. Shelly et al. [2007] attempted ...

Energy Technology Data Exchange (ETDEWEB)

The unknown {beta}-decay half-lives of 22 isotopes far off stability (5 < T{sub Z} < 10) in the region from Ti to Ni were measured at GSI, Darmstadt. The nuclei were produced in a fragmentation reaction of 500 A.MeV {sup 86}Kr-projectile impinging on a thick Be target. The isotopes of interest were separated and identified with the fragment separator, FRS, by a combination of B{rho},Z, and ToF techniques. An additional range separation was performed by a selective implantation into granular detectors. The spatial and time correlations of the implant with the consecutively detected {beta}-particles were used to determine the unknown half-lives. For nuclei far off stability, {beta}-decay chains were measured and analyzed as well, leading to an even more reliable evaluation of the lifetimes. The large discrepancies found between the measured and the theoretical values emphasize that most recent theoretical work is not an improvement over ...

International Nuclear Information System (INIS)

The low excitation energy spectroscopy of "8"6Sr, "8"8Sr, "8"9Sr, "8"6Rb, and "8"7Rb nuclear systems was studied via one-nucleon transfer reactions. The strontium isotopes, "8"7Sr and "8"8Sr, were used as targets in this study. Spectroscopic strengths were extracted from the measured transfer reaction cross sections and the distorted wave Born approximation (DWBA) analysis. Efforts have been made to accomplish a complete detection of spectroscopic strengths through the excitation energy region where levels can be resolved and identified. A shell model sum rule analysis is then made. Diagonal matrix elements for the effective two-nucleon interaction were deduced from empirical energy centroid. Matrix elements normalized by their empirical monopole energy was plotted against the semiclassical angle between two spins. They were compared with various analytical function forms of the effective two-nucleon interaction depending on their spins, ...

Energy Technology Data Exchange (ETDEWEB)

Soils and groundwater beneath an abandoned Process sewer line in the A/M Area of the Savannah River Site (SRS) contain elevated levels of volatile organic compounds, specifically trichloroethylene (TCE) and tetrachloroethylene (PCE), two common chlorinated solvents. These compounds have low aqueous solubilities, thus when released to the subsurface in sufficient quantity, tend to exist as immiscible fluids or nonaqueous phase liquids (NAPLs). Because chlorinated solvents are also denser than water, they are referred to by the acronym DNAPLS, or dense non aqueous Phase liquids. Technologies targeted at the efficient characterization or removal of DNAPL are not currently proven. For example, most DNAPL studies rely on traditional soil and water sampling and the fortuitous observation of immiscible solvent. Once DNAPL is identified, soil excavation (which is only applicable to small contained spill sites) is the only ``proven`` cleanup method. New ...

International Nuclear Information System (INIS)

The purpose of organization and management development activities in the commercial nuclear power industry is to foster high levels of power plant performance and safety through improved human performance. The NRC has been working to develop assessment tools to assay the effects of organizational factors on plant safety. The utility industry has been working on initiatives targeting individual accountability, the improvement of plant performance and the elimination of the items identified through the NRC assessment process. Organization and management activities do not focus on industry organizational charts, but on the personnel processes and dimensions (factors) that affect safety and economic performance. As individual terms these activities are often combined and referred to as organizational factors. As an area of study, organizational factors has become more prominent as the industry emphasis has switched in recent years from hardware ...

Science.gov (United States)

Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single E2F cis-acting binding site. Correspondingly with the reported opposite effect of light on the E2Fb and E2Fc ...

British Library Electronic Table of Contents (United Kingdom)

MicroRNAs (miRNAs) are small non-coding RNAs that play vital roles in plant abiotic stress responses via cleavage or translational inhibition of their target mRNAs. Populus euphratica is a typical stress-resistant sessile organism that grows in desert areas. Here, we identified sequences of 12 miRNA precursors from 11 families and 13 mature miRNAs from 12 families by PCR amplification in P. euphratica. To detect expression differences in mature miRNAs and their precursors under dehydration and high salinity shock in P. euphratica, we examined 14 miRNA precursors from 13 miRNA families and 17 mature miRNAs from 17 miRNA families using the SYBR Green RT?PCR assay. This is the first report of expression profiles for both precursor and mature miRNAs in P. euphratica. By profiling both the matu...

Energy Technology Data Exchange (ETDEWEB)

With an objective to discuss applicability of resistivity imaging using electromagnetic migration to detection of underground cavity, an applicability test was carried out on calculation of a numerical model and measurement data. By using the numerical model, a calculation was performed on a hypothetical case that a cubic cavity with sides each at 40 m exists in a homogenous medium of 200 ohm-m, with the cavity top located 20 m below the ground surface. As a result, it was possible to structure in a very short calculation time an image of the cavity which cannot be identified by one-dimensional inverse analysis. In the case of this cavity, a center of the image was structured on its lower face. It was shown that a location to indicate the image must be changed according to difference in the measurement locations. In a test on data measured in an underground cavity in the city of Utsunomiya, Tochigi Prefecture, it was found that the result may vary largely depending ...

International Nuclear Information System (INIS)

An uncertainty decrease is an very important issue for enhancing risk-informed (RI) activities worldwide. Especially, a relatively large uncertainty in a level-2 (L2) PSA risk compared with level-1 internal PSA risk has been a bottleneck problem in the RI application to the extent of a severe accident management. According to the ASME PRA standard in which sources of an uncertainty to capture a category-II RI (= Option 2) capability are listed, an uncertainty analysis which identifies the key sources of an uncertainty and includes sensitivity studies for dominant contributors to LERF (Large Early Release Frequency) needs to be provided. To solve these problems, USNRC have developed the 'SPAR-LERF' model related to the L2 RI application and 'L2 uncertainty assessment and improvement' work is being taken as a main PSA2 topic of the SARNET (Severe Accident Research Network of Excellence) program in Europe by OECD/NEA. Domestically, a mid/long-term R and D is being ...

International Nuclear Information System (INIS)

These experiments were performed on the Isocele separator, on-line with the Orsay synchrocyclotron; thulium isotopes were produced by bombarding natural erbium targets with 150nA beam of 157MeV protons. Two Ge(Li) detectors, with resolution of 2.3 and 2.5keV at 1332keV used for #gamma#-ray measurements; conversion electron spectra were measured using a Si(Li) detector. #gamma# spectra, #gamma#-#gamma# coincidence and conversion electron measurements were sufficient to build the flow energy level schemes of the transitional "1"5"8Er and "1"5"6Er nuclei. On both nuclei several quasi rotational bands have been identified. These results are compared with other even erbium isotopes and with the neighboring N=88 and 90 isotones. Comparisons with predictions issued from some classical models are also performed: "1"5"8Er appears as a deformed nucleus very similar to "1"6"0Er and "1"6"2Er; on the other hand "1"5"6Er seems to be a soft vibrational ...

Energy Technology Data Exchange (ETDEWEB)

The purified integral membrane protein, band 3, from human erythrocytes was inserted into egg lecithin liposomes. The insertion of band 3 was determined from thermal transition data from the analysis of the C-H stretching region bands recorded at temperatures from 25 to -22[sup o]C. Raman spectra show that band 3 considerably broadens and lowers the thermal transition of egg lecithin liposomes, suggesting the insertion of band 3. The band 3-inserted liposomes were irradiated with gamma-rays (40 Gy) and the radiation target groups were determined by the analysis of the structural sensitive Raman bands in the 1600-1700 cm[sup -1] (amide I), 1200-1300 cm[sup -1] (amide III) and 550-1030 cm[sup -1] (side chain amino groups) regions. The radiation-sensitive groups as identified from Raman spectra in the region 550-1030 cm[sup -1] are tyrosines and cysteines. The radiation-induced changes in the secondary structure were determined from amide I and ...

Science.gov (United States)

PURPOSE: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment thus requiring innovative and effective targeted therapies. The oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates insulin-like growth factor binding protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function.EXPERIMENTAL DESIGN: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarray and real-time PCR and ELISA in human HCC cell lines. Dual Fluorescence in situ hybridization was performed to detect loss of heterozygosity at IGFBP7 locus. Stable IGFBP7-overexpressing clones were established in the background of AEG-1-overexpressing human HCC cells and were analyzed for in vitro proliferation and senescence and in vivo tumorigenesis and ...

Science.gov (United States)

The purpose of this project was to demonstrate targeted infill and extension drilling opportunities, better determinations of oil-in-place, and methods for improved completion efficiency. The investigations and demonstrations were focussed on Red River and Ratcliffe reservoirs in the Williston Basin within portions of Montana, North Dakota and South Dakota. Both of these formations have been successfully explored with conventional 2-dimensional (2D) seismic. Improved reservoir characterization utilizing 3-dimensional (3D) seismic was investigated for identification of structural and stratigraphic reservoir compartments. These seismic characterizations were integrated with geological and engineering studies. The project tested lateral completion techniques, including high-pressure jetting lance technology and short-radius lateral drilling to enhance completion efficiency. Lateral completions should improve economics for both primary and secondary oil where low ...

International Nuclear Information System (INIS)

This paper reviews three key initiatives undertaken in the historical city of Oxford to bring about reductions in energy-related CO_2 emissions on a city-wide scale. The author has been part of all the three initiatives. In 2002, a collaborative partnership between academia, industry and city council started the Oxford Solar Initiative (OSI) which uses a community-based approach to help households and organisations in Oxford, financially and technically, to install solar energy systems and energy efficiency measures in buildings. So far OSI has facilitated the installation of 80 active solar systems, over 450 energy efficiency measures and 3,000 low energy bulbs. The scientific basis of OSI is a GIS-based DECoRuM model which estimates and maps baseline energy use and CO_2 emissions on a house-by house level, identifies 'pollution' hotspots, predicts the potential for reductions in CO_2 emissions and monitors reductions achieved as a result of deploying energy ...

UK PubMed Central (United Kingdom)

Background and ObjectivesClopidogrel resistance or low-responsiveness may be associated with recurrent atherothrombotic events after drug-eluting stent (DES) implantation. We prospectively...Full Text Available

International Nuclear Information System (INIS)

Synthesis of the azido substituted non-steroidal anti-inflammatory drug 2-(2,6-dichloroanilino)phenylacetic acid and isotope labeling of this compound have been performed and are described. Initial evaluation of the binding ability and photoreactivity indicates that this compound has potential for photoaffinity labeling as well as enzyme selectivity studies. (author).

Energy Technology Data Exchange (ETDEWEB)

These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. Volume II presents procedures for the entrapment of a number of drugs, including genetic material, into selected types of liposomes.

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The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)

UK PubMed Central (United Kingdom)

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available

UK PubMed Central (United Kingdom)

The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown....Full Text Available

UK PubMed Central (United Kingdom)

Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human...Full Text Available

UK PubMed Central (United Kingdom)

Computational prediction of microRNA targets remains a challenging problem. The existing rule-based, data-driven and expression profiling approaches to target prediction are mostly approached from the...Full Text Available

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Development in Instrumentation and Control (I and C) technology provides more convenience and better performance, thus, adopted in many fields. To adopt newly developed technology, nuclear industry requires rigorous V and V procedure and tests to assure reliable operation. Adoption of digital system requires verification and testing of the OS for licensing. Commercial real-time operating system (RTOS) is targeted to apply to various, unpredictable needs, which makes it difficult to verify. For this reason, simple, application-oriented realtime OS is developed for the nuclear application. In this work, we show how to verify the developed RTOS at each development lifecycle. Commercial formal tool is used in specification and verification of the system. Based on the developed model, software in C language is automatically generated. Tests are performed for two purposes; one is to identify consistency between the verified model and the generated ...

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Concentrating solar power (CSP) technologies continue to mature and are being deployed worldwide. Power towers will likely play an essential role in the future development of CSP due to their potential to provide dispatchable solar electricity at a low cost. This Power Tower Technology Roadmap has been developed by the U.S. Department of Energy (DOE) to describe the current technology, the improvement opportunities that exist for the technology, and the specific activities needed to reach the DOE programmatic target of providing competitively-priced electricity in the intermediate and baseload power markets by 2020. As a first step in developing this roadmap, a Power Tower Roadmap Workshop that included the tower industry, national laboratories, and DOE was held in March 2010. A number of technology improvement opportunities (TIOs) were identified at this workshop and separated into four categories associated with power tower subsystems: solar ...

British Library Electronic Table of Contents (United Kingdom)

Experimental and computational investigations were performed in order to better understand the mechanical response of rigid targets with various geometries to the detonation of shallow buried explosives. The motion of the targets was measured by use of high-speed digital video photography. This work involved flat targets, targets that were downwardly convex, and targets that were downwardly concave with explosive charges located at various positions beneath the targets. It was observed that, in general, angled hulls - whether downwardly concave or convex - tended to reduce the amount of momentum imparted to the center of mass of the targets. Computations were performed by use of an arbitrary Langrangian-Eulerian treatment in a nonlinear finite element code. A model based on quasi-static te...

International Nuclear Information System (INIS)

The design of the absorber blocks for internal and external dumping of the SPS proton beam is discussed. In addition, the external target stations for slow and fast extracted proton beams are described.

Science.gov (United States)

Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...

International Nuclear Information System (INIS)

The National Ignition Facility (NIF) is a proposed Department of Energy facility which will contribute to the resolution of important Defense Program and inertial fusion energy issues for energy production in the future. The NIF will consist of a laser system with 192 independent beamlets transported to a target chamber. The target chamber is a multi-purpose structure that provides the interface between the target and the laser optics. The chamber must be capable of achieving moderate vacuum levels in reasonable times; it must remain dimensionally stable within micron tolerances, provide support for the optics, diagnostics, and target positioner; it must minimize the debris from the x-ray and laser light environments; and it must be capable of supporting external neutron shielding. The chamber must also be fabricated from a low neutron activation material. The fusion reaction in the ...

Science.gov (United States)

Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of functional selectivity for the three serotonin receptors. Interestingly, the non-hallucinogenic compound ...

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...the School, the research group structure was recently revised and now comprises the following teams: Drug Design and Analysis Pharmaceutics Pharmacy Practice and Policy Pharmacological and Biomedical Science The current structure was designed to take into account the future development of research in the academic area. The ...Discovery, Molecular Modelling, Pharmacology and Molecular Biology) and international recognition (Biological Sciences), which have now been re-organised into the Drug Design and Analysis and Pharmacological and Biomedical Sciences teams. The reorganisation also aimed to improve the research reputation of the other teams. The improvements in ... Email to a friend Print Within this area Drug design and analysis Pharmaceutics Pharmacy practice and policy Pharmacological and biomedical sciences Projects Publications Staff Considering a course? Research Degrees Course Finder Order a Prospectus Subject ...

British Library Electronic Table of Contents (United Kingdom)

Propanolol is a betablocker drug used in the treatment of arterial hypertension related diseases. In order to achieve an optimal performance of this drug it is important to consider the possible interactions of propanolol with plasma proteins. In this work, we have used several experimental techniques to characterise the effect of addition of the betablocker propanolol on the properties of bovine plasma fibrinogen (FB). Differential scanning calorimeter (DSC), circular dichroism (CD), dynamic light scattering (DLS), surface tension techniques and atomic force microscopy (AFM) measurements have been combined to carry out a detailed physicochemical and surface characterization of the mixed system. As a result, DSC measurements show that propranolol can play two opposite roles, either acting ...

British Library Electronic Table of Contents (United Kingdom)

Introduction: The QT interval of the electrocardiogram (ECG) reflects the duration of ventricular depolarization and repolarization. A drug-induced prolongation of ventricular repolarization, and thereby QT prolongation, is recognized to be a marker for an enhanced risk for ventricular arrhythmia. The assessment of a drug's effect on the QT interval has therefore become routine within pharmaceutical research and development. However, the heart rate has a major influence on the QT interval; the QT interval shortens as heart rate increases such that one needs to account for such heart rate-dependent changes when evaluating possible drug-induced effects on the QT interval. The relationship between the QT interval and heart rate can be modeled mathematically and using this function a so-called...

British Library Electronic Table of Contents (United Kingdom)

Breath analysis could offer a non-invasive means of intravenous drug monitoring if robust correlations between drug concentrations in breath and blood can be established. In this study, propofol blood and breath concentrations were determined in an animal model under varying physiological conditions. Propofol concentrations in breath were determined by means of two independently calibrated analytical methods: continuous, real-time proton transfer reaction mass spectrometry (PTR-MS) and discontinuous solid-phase micro-extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS). Blood concentrations were determined by means of SPME-GC-MS. Effects of changes in pulmonary blood flow resulting in a decreased cardiac output (CO) and effects of dobutamine administration resulting in...

Energy Technology Data Exchange (ETDEWEB)

We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)

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Short communication.

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Science.gov (United States)

... 4. Military Working Dogs iMWDs). As used in this Instruction refers to drug detector dogs only. 5. Military Working Doq Executive Agent M(WJDEMA. ...

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... J. W. and R. A. de Zeeuw. 1990. Transdermal drug delivery: efficacy and potential applications of the penetration enhancer ... ...

UK PubMed Central (United Kingdom)

Previous studies have shown that salicylates and protein-calorie malnutrition independently compromise maturation and growth of infants. In the present study, pregnant rats were fed normal-and low-protein...Full Text Available

UK PubMed Central (United Kingdom)

Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer...Full Text Available

UK PubMed Central (United Kingdom)

Chronic pain patients who show aberrant drug-related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundPostoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat...Full Text Available

UK PubMed Central (United Kingdom)

SummaryBackgroundThe US FDA has been collecting information on medical devices involved in significant adverse advents since 1984. These reports have...Full Text Available

UK PubMed Central (United Kingdom)

IntroductionRecent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers’...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

The effect of adriamycin in combination with radiation on the skin reactions of mouse feet has been examined under a variety of experimental conditions including: (a) hyperthermic treatment of the foot immediately following adriamycin administration, with the former given either just before or just after x irradiation, and (b) fractionated treatments of drug and radiation in a variety of sequences over an 18-day period. In the case of the most severe hyperthermic treatment, no increased radiation reactions were observed in the presence of adriamycin. However, in the case of the less severe hyperthermic treatment a small but significant increase in skin reactions was observed. In the study of fractionated drug and radiation treatments, an enhancement of reaction in those animals receiving combined modality treatment over those receiving radiation alone was seen in those groups where the initiation of drug treatment succeeded ...

UK PubMed Central (United Kingdom)

The in vivo antichlamydial activities of sparfloxacin and reference drugs were examined in a experimental model of pneumonia caused by Chlamydia pneumoniae in leukopenic mice; their in vitro activities...Full Text Available

UK PubMed Central (United Kingdom)

Indomethacin, a potent nonsteroidal anti-inflammatory drug, has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of indomethacin produces...Full Text Available

UK PubMed Central (United Kingdom)

The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD),...Full Text Available

UK PubMed Central (United Kingdom)

Current drug treatments for post-menopausal osteoporosis cannot eliminate bone fractures, possibly because the mechanisms responsible for bone loss are not fully understood. Although research within...Full Text Available

UK PubMed Central (United Kingdom)

Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment, N-acetylcysteine (NAC), has a limited...Full Text Available

UK PubMed Central (United Kingdom)

The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of...Full Text Available

UK PubMed Central (United Kingdom)

Neonatal bacterial infection in rats alters the responses to a variety of subsequent challenges later in life. Here we explored the effects of neonatal bacterial infection on a subsequent drug...Full Text Available

UK PubMed Central (United Kingdom)

Mycophenolate mofetil (MMF) is an immunosuppressive drug that acts as a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH). MMF has recently been shown to inhibit the enzymatic activity...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available

UK PubMed Central (United Kingdom)

DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced...Full Text Available

UK PubMed Central (United Kingdom)

The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either...Full Text Available

UK PubMed Central (United Kingdom)

A growing number of studies suggest that the development of compulsive drug seeking and taking depends on dorsostriatal mechanisms. We previously observed that ex vivo acute...Full Text Available

UK PubMed Central (United Kingdom)

Infection due to multidrug resistance pathogens is difficult to manage due to bacterial virulence factors and because of a relatively limited choice of antimicrobial agents. Thus, it is imperative to...Full Text Available

UK PubMed Central (United Kingdom)

Somatic cell nuclear transfer or therapeutic cloning has provided great hope for stem cell-based therapies. However therapeutic cloning has been experiencing both ethical and technical difficulties....Full Text Available

UK PubMed Central (United Kingdom)

The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundMethamphetamine (METH), an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundControl of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age...Full Text Available

UK PubMed Central (United Kingdom)

The full impact of secondary stigma (stigma directed at family) on an HIV-positive individual is unknown. This qualitative research explores perceptions of secondary stigma in the Vietnamese...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

The D2 antidopaminergic drug Domperidone was evaluated singly and in combination with synthetic adrenocorticoid and an H2 antihistamine for its ability to reduce the acute emetic effects of /sup 60/Co whole-body radiation. Random-source adult male dogs were fasted 12 hours, fed a standard meal, injected 44 minutes later and irradiated 47 minutes after that. Four groups of dogs were radiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim+Thi), and dexamethasone + domperidone + cimetidine (Dex+Dom+Cim). Drug quantities for dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 ka, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset times, offset times, and number of episodes were recorded. The ED50 of Dex+Dom+Cim was higher than Con. Dom ...

UK PubMed Central (United Kingdom)

Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available

UK PubMed Central (United Kingdom)

1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2...Full Text Available

Science.gov (United States)

Antivenoms are the currently available agents for treatment of snake venom intoxication in humans. The development of therapeutic strategies employing more generally available drugs could improve treatment of invenomation by reducing hypersensitive reacti...

UK PubMed Central (United Kingdom)

The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated....Full Text Available

UK PubMed Central (United Kingdom)

The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs...Full Text Available

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Experiments were performed to investigate the involvement of the cell membrane in the excision DNA repair process in Escherichia coli. Two membrane-binding drugs, procaine and phenethyl alcohol (PEA), inhibited liquid-holding recovery (LBR) in u.v.-irradiated E. coli wild-type and recA strains. In uvrB and polA strains where, after u.v.-irradiation, LHR was absent the two drugs had no effect. Both drugs markedly reduced the removal of u.v.-induced thymine dimers in the DNA of wild-type cells (H/r30). Analysis by alkaline sucrose gradients revealed that PEA inhibited the incision step in excision repair. In contrast, procaine had no effect on incision but apparently inhibited the late steps in excision repair. PEA dissociated DNA from the cell membrane, whereas procaine did not. The results suggest that the two drugs PEA and procaine inhibit LHR and the excision repair process operating on u.v.-induced ...

UK PubMed Central (United Kingdom)

Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States....Full Text Available

UK PubMed Central (United Kingdom)

Aims:To investigate the relationship between the duration of comatose state, severity of rhabdomyolysis and frequency of peripheral nerve injury (PNI) in patients following...Full Text Available

UK PubMed Central (United Kingdom)

Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several...Full Text Available

UK PubMed Central (United Kingdom)

We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs....Full Text Available

Science.gov (United States)

The main objective of Phase I of this SBIR project was to demonstrate the feasibility for successful development of an antimicrobial wound dressing based on a hydrogel sustained release matrix. This goal has been achieved. In vitro studies of drug diffusi...

UK PubMed Central (United Kingdom)

Oligopeptidic drugs such as β-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model...Full Text Available

UK PubMed Central (United Kingdom)

Albumin is a multifunctional transport protein that binds a wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation of the epsilon-amino group...Full Text Available

UK PubMed Central (United Kingdom)

Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although...Full Text Available