Convection-enhanced delivery (CED) has emerged as a promising method of targeteddrug-delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate...Full Text Available
The main goal of local drugdelivery is to increase the concentration of a specific therapeutic agent in a target tissue with minimal nontarget distribution. Compared to systemic therapy, local drugdelivery provides a high level of therapeutic efficacy with minimal systemic effects. The current primary imaging modality for drugdelivery has been x-ray angiography, but it has major limitations including anatomical ambiguity and inability to visualize the targeted tissues. Due to these inherent problems, MR guidance has been explored as an alternative imaging modality for guiding and monitoring of drug therapy. Recently, interventional MR (XMR) systems have been implemented that have both dual x-ray and MRI capabilities in a single suite and allow for real-time interventional procedures to ...
To capitalize on the response of tumor cells to ionizing radiation, we developed a controlled-release nanoparticle drugdelivery system using a targeting peptide that recognizes a radiation-induced...Full Text Available
Magnetic particles have become very promising materials for drugdelivery. 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 ...
A novel drugdelivery 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
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 drugdelivery. 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...
Magnetic drugtargeting, 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 ...
Convection-enhanced drugdelivery (CED) is a novel approach to delivering drugs into brain tissue. Drugs are delivered continuously via a catheter, enabling large volume distributions of high drug concentrations...Full Text Available
The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry (DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2 cells were analyzed by means of spectro...
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 targeteddrug action and might be a good therapeutic avenue in combating infectious GI disorders.
The treatment of brain disorders is one of the greatest challenges in drugdelivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the...Full Text Available
Abstract Many solute carrier transporters that interact with anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of membrane transporters responsible for the influx of physiological substances including oligopeptides, amino acids, and organic cations and anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced oligopeptide H+/peptide cotransporter 1 activity in cancer cells is useful for tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes. Amino acid transporters such as...
We investigate a method for gene delivery to vascular smooth muscle cells using ultrasound triggered delivery of plasmid DNA from electrostatically coupled cationic microbubbles. Microbubbles...Full Text Available
Purpose:This study investigated the penetration of lidocaine around and through a sutured incision following the application of iontophoretic and passive patches...Full Text Available
BackgroundParticulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the...Full Text Available
This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal ...
Gastrointestinal patches represent a novel multiparticulate drugdelivery 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...
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
The magnetic separation technology using sub-microsized ferromagnetic particle is indispensable in many areas of medical biosciences. For example, ferromagnetic particles (200-500 nm) are widely used for cell sorting in stem cell research with the use of cell surface-specific antigens. Nanosized ferromagnetic particles (10-20 nm) have been suggested as more suitable in drugdelivery studies given their efficiency of tissue penetration, however, the magnetic separation method for them has not been established. One of the major reasons is that magnetic force acting on the object particles decreases drastically as a particle diameter becomes small. In this study, magnetic force acting on the targets was enhanced by the combination of superconducting magnet and the filter consisting of ferromagnetic particle. By doing so, we confirmed that Fe{sub 3}O{sub 4} of 20 nm in diameter was trapped in the magnetic filter under an ...
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
The use of X-ray scattering techniques in pharmaceutical science is increasing, in part through increased collaborations with the materials science community, and through increased availability of instrumentation, particularly synchrotron sources. The ability to understand not only the biopharmaceutical outcome, but also arguably, more importantly, the structural aspects of drugs and drugdelivery systems, is essential to progressing pharmaceutical science; this review serves as an introduction to the major techniques and the wide range of areas in which X-ray scattering may be applied in understanding and controlling structure in pharmaceutical systems.
Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary...Full Text Available
BackgroundIntrafractional motion results in local over- and under-dosage in particle therapy with a scanned beam. Scanned beam delivery offers the possibility to compensate target...Full Text Available
Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend...Full Text Available
BackgroundCalcium homeostasis is a known target of several environmental toxicants including lead and mercury.ObjectiveOur goal was to determine...Full Text Available
The cephalosporin class antibacterial agent, cefazolin, was intercalated into layered double hydroxides (LDHs) in order to improve the drug efficiency as well as to achieve the controlled release property. Cefazolin molecules were incorporated into LDH through conventional ion exchange reaction. X-ray diffraction pattern analyses confirmed that cefazolin molecules were intercalated between the interlayer spaces of LDH. Fourier-transform infrared spectra and high performance liquid chromatographs clearly showed that the drug molecules were stabilized in LDH lattice through electrostatic interaction and released without any changes in their chemical integrity. Antibacterial activity of the cefazolin-LDH nanohybrid was also examined by an in vitro test, such as the minimal inhibitory concentr...
In this paper, we prepared a novel cationic self-assembled micelle from poly(epsilon-caprolactone)-poly(ethyl glycol)-poly(epsilon-caprolactone) grafted polyethyleneimine (PCEC-g-PEI). The PCEC-g-PEI micelles, formed by self-assembly method, had mean particle size of ca. 82 nm and zeta potential of +22.5 mV at 37 degrees C, and could efficiently transfer pGFP into HEK293 cells in vitro. Meanwhile, as a model hydrophobic chemotherapeutic drug, honokiol was loaded into PCEC-g-PEI micelles by direct dissolution method assisted by ultrasonication. The honokiol loaded cationic PCEC-g-PEI micelles could effectively adsorb DNA onto its surface, while it could release honokiol in an extended period in vitro. This study demonstrated a novel DNA and hydrophobic chemotherapeutic drug co-delivery system. PMID:21121283
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)
A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO−)]...Full Text Available
BackgroundStem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells...Full Text Available
BackgroundGene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drugtargets....Full Text Available
The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA...Full Text Available
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
Drug particle size distribution has a profound impact to the content uniformity in low-dose solid drug products. We derived theoretically the skewness of potency distribution as a function of particle size distribution and target dose. It was demonstrated that both skewness and coefficient of variation diverge simultaneously with inverse square root of the target dose. This scaling relation was observed in recent experiment and was verified by Monte Carlo (MC) simulation, which was employed for the first time to solve for the full potency distribution from a random retrieving model. When tested against the criteria from USP uniformity of dosage units, MC simulation showed a striking anisotropic distribution of the data. This suggests a full-scale consideration of the potency distribu...
Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drugdelivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunize...
Polyurethane (PU) foam was combined with protein drug-loaded pH-sensitive alginate-bentonite hydrogel for wound dressings. Alginate is a linear copolymer composed of 1?4-linked ?-D-mannuronic acid (M) and its c-5-epimer ?-Lguluronic acid (G). The amount of (M) and (G) and their sequential distribution are varied depending on the alginate source. Soluble sodium alginate can become a hydrogel when cross-linked with divalent cations and has widespread applications in the food, drink, pharmaceutical and bioengineering industries. Recently, it has been also proposed as a biomaterial for drugdelivery systems. Bentonites are the natural inorganic polymers consisting of a large proportion of expandable clay minerals with a three-layer structure such as montmorillonite, beidellite, nontronite, etc...
This review begins with an historical account of biomaterials applications followed by a concise description of the phenomena taking place between the living tissues and non-living materials containing them. After describing the requirements for biodegradability and the mechanisms involved, a thorough literature survey of such polymers is presented. In the end a very short review of the work done in this area by the authors in recent years is given, including: the synthesis of a wide variety of biodegradable di-and tri-block copolymers, preparation of microparticles; stealth-and immuno-liposomes; dendrosomes and polymersomes; and some of their applications in drug and gene delivery.
Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic ...
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...
The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drugtargets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination d...
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 ...
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...
The iodinated oil lipiodol is commonly used as a carrier for in situ delivery of drugs or radioactivity to hepatic tumors. Recently, we reported a new kit formulation for high-activity labeling of lipiodol with the {beta}-emitting radionuclide Re-188. Since the whole preparation involves different steps and complex manipulations of high-activity samples, we describe here an automated synthesis module that allows the easy preparation of sterile and pyrogen-free samples of Re-188 lipiodol ready to be administered to the patient. Important advantages include the possibility to incorporate high Re-188 activity into the lipiodol hydrophobic phase and a sharp reduction of radiation exposure of the operator assisting the labelling procedure. Application of this modular reaction system could be also extended to the preparation of other Re-188 radiopharmaceuticals and to compound labelled with different {beta}-emitting therapeutic radionuclides.
This work showed the formation of phospholipid vesicle coating on inorganic sericite surface with characterization by combining electron microscopy of FE-SEM, TEM, AFM, and qualitatively evaluated the coated phospholipid vesicle by XPS as a function of etching time. The possibility of phospholipid vesicle mobility on the surface was restrained by the chelation effect of magnesium cation. The stabilization properties of phospholipid vesicles on sericite surface were demonstrated by the various concentration of magnesium cation. The presence of magnesium was found to have a much more pronounced influence on the lipid deposition process. The Mg cation plays an important role for attaching the phospholipids with optimum concentration of 7 mM. Totally, the phospholipid vesicles coating on inorganic powder could be useful for bio-related fields such as cosmetics and drugdelivery system as the key functional compounds. We hope this basic result lead ...
The purpose of this study was to prepare recombinant human epidermal growth factor (rhEGF) collagen sponges for topical applications and investigate the effects of different types of crosslinked collagen sponges as platforms for the controlled release of rhEGF. The microstructure and the drug release rates of collagen sponges were modified through treatment with different types (glutaraldehyde (GTA), genipin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)), different concentrations of crosslinking agents and various preparation conditions. A controlled release profile was observed for the crosslinked collagen sponges as compared to the non-crosslinked ones. The results indicated that the GTA crosslinked sponges have the most potent controlling effect. As the amount of GTA increased, a greater rigidity of the collagen sponge structure combined with a lower hydrophilicity was observed, leading to a decreased drug release rate and an ...
A promising drugtarget currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...
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 ...
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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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-targeteddrugs 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...
Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagoni...
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.
The Pawtucket Heart Health Program is one of the community studies examining whether population-based efforts to lower cardiovascular risk factors will reduce cardiovascular morbidity and mortality. The Pawtucket Heart Health Program intervention is based on a blend of social learning theory, community organization models, community psychology tenets, and diffusion research. This model allows for multifaceted programs that target individuals, groups, organizations, and the entire community to alter their cardiovascular risk through managing blood pressure, lowering blood cholesterol, quitting smoking, increasing fitness, and maintaining desirable weight levels. A dominant feature of the intervention is the emphasis that it places on volunteers for program delivery. The role of volunteers in providing direct services to help citizens lower their blood pressure and lose weight is highlighted to demonstrate the feasibility and effectiveness of ...
Vulnerability to abused drugs is influenced by multiple genes unique to each drug as well as to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly,...Full Text Available
By contrast to the large mass, complexity and recirculating power of conventional drivers for inertial confinement fusion (ICF), antiproton annihilation offers a specific energy of 90MJ/{micro}g and thus a unique form of energy packaging and delivery. In principle, antiproton drivers could provide a profound reduction in system mass for advanced space propulsion by ICF. We examine the physics underlying the use of antiprotons ({bar p}) to drive various classes of high-yield ICF targets by the methods of volumetric ignition, hotspot ignition and fast ignition. The useable fraction of annihilation deposition energy is determined for both {bar p}-driven ablative compression and {bar p}-driven fast ignition, in association with 0-D and 1-D target burn models. Thereby, we deduce scaling laws for the number of injected antiprotons required per capsule, together with timing and focal spot requirements. The kinetic energy of the ...
Optimization of nonviral gene delivery typically focuses on the design of particulate carriers that are endowed with desirable membrane targeting, internalization, and endosomal escape properties. Topographical control of cell transfectability, however, remains a largely unexplored parameter. Emerging literature has highlighted the influence of cell-topography interactions on modulation of many cell phenotypes, including protein expression and cytoskeletal behaviors implicated in endocytosis. Using high-throughput screening of primary human dermal fibroblasts cultured on a combinatorial library of microscale topographies, we have demonstrated an improvement in nonviral transfection efficiency for cells cultured on dense micropit patterns compared to smooth substrates, as verified with flow...
The need for safe food products has motivated food scientists and industry to find novel technologies for antimicrobial delivery for improving food safety and quality. Controlled release packaging is a novel technology that uses the package to deliver antimicrobials in a controlled manner and sustain antimicrobial stress on the targeted microorganism over the required shelf life. This work studied the effect of controlled release of nisin to inhibit growth of Micrococcus luteus (a model microorganism) using a computerized syringe pump system to mimic the release of nisin from packaging films which was characterized by an initially fast rate and a slower rate as time progressed. The results show that controlled release of nisin was strikingly more effective than instantly added (?formulated...
There is increasing use of radiofrequency radiation (RFR) in industry for communications, welding, security, radio, medicine, navigation etc. It has been recognised for some years that RFR may interact with cardiac pacemakers and steps have been taken to prevent this interference. It is less well recognised that other metallic implants may also act as antennas in an RFR field and possibly cause adverse health effects by heating local tissues. There are a large and increasing number of implants having metal components which may be found in RFR workers. These implants include artificial joints, rods and plates used in orthopaedics, rings in heart valves, wires in sutures, bionic ears, subcutaneous infusion systems and (external) transdermal drugdelivery patches"1. The physician concerned with job placement of such persons requires information on the likelihood of an implant interacting with RFR so as to impair health. The following outlines the ...
A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) system is described. The system is being designed to deliver fast IMPT so that larger target volumes and motion management can be accomplished. The system will be ideal for large and complex target volumes in young patients. The basis of the design is the dielectric wall accelerator (DWA) system being developed at the Lawrence Livermore National Laboratory (LLNL). The DWA uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. High electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The system will produce individual pulses that can be varied in intensity, energy and spot width. The IMPT planning system will optimize delivery characteristics. The system will be capable of being sited in a ...
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 ...
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
We consider a serial supply chain consisting of a raw material supplier, a manufacturer, a distribution centre and a retailer in the presence of time-varying delivery between manufacturer facility and the retailer warehouse. Delivery time functions are developed based on practical data analysis and the cost models for both linear and non-linear delivery time functions are derived. Analytic solution for system with linear delivery times is derived and a search algorithm for system with non-linear delivery times is established. Finally, sensitivity analysis is made to help decision makers achieve a lower total cost in practice.
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...
The present study was carried out to exploit the feasibility of using polymeric nanosponges as an alternative carrier for targeting econazole nitrate (EN) to the skin through topical hydrogel formulation. Nanosponges prepared by emulsion solvent diffusion method were evaluated for various physicochemical parameters and in vitro drug release. The nanosponges of EN were discrete free flowing nanosized particles with perforated orange peel like morphology as visualized by SEM. The nanosponge formulated using PVA:EC (3:2) displayed highest in vitro release after 12 ?h in phosphate buffer (pH 6.8) that fitted matrix model. Selected nanosponge was formulated as Carbopol 934 NF hydrogel using varying concentrations of permeation enhancers propylene glycol and N-methyl-2-pyrrolidone. The EN nanosp...
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...
Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drugtarget for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...
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...
Abstract The authors provide a survey of how images are used in radiation therapy to improve the precision of radiation therapy plans, and delivery of radiation treatment. In contrast...Full Text Available
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...
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two ...
Full text: Radiotherapy treatment planning (RTP) relies heavily on medical imaging. Until recently, the most important planning tool was the treatment simulator. The kilovoltage radiographic capabilities in a treatment simulator enabled the boundaries of treatment fields to be visualized with respect to bony anatomic landmarks. Perhaps the most important advance in treatment planning in recent years is the ability to visualize the passage of the beams with respect to a more accurate geometrical representation of the tumor and other soft tissue structures. This 'virtual simulation' uses a computer-based representation of a patient to determine the extent of the disease and the location of radiation sensitive normal tissue. Computer tomographic (CT) imaging produces a high-resolution three-dimensional representation of anatomy that can be correlated with other image sets such as magnetic resonance images (MRI) of function. Positron emission tomographic (PET) imaging is beginning to be ...
Autophagy is an intracellular recycling route in eukaryotes whereby organelles and cytoplasm are sequestered in vesicles, which are subsequently delivered to the vacuole for breakdown. The process is induced by various nutrient-responsive signaling cascades converging on the Autophagy-Related1 (ATG1)/ATG13 kinase complex. Here, we describe the ATG1/13 complex in Arabidopsis thaliana and show that it is both a regulator and a target of autophagy. Plants missing ATG13 are hypersensitive to nutrient limitations and senesce prematurely similar to mutants lacking other components of the ATG system. Synthesis of the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts, which are essential for autophagy, still occurs in ATG13-deficient plants, but the biogenesis of ATG8-decorated autophagic bodies does not, indicating that the complex regulates downstream events required for autophagosome enclosure and/or vacuolar delivery. Surprisingly, levels of the ...
Megavoltage photon intensity-modulated radiation therapy (IMRT) is typically used in the treatment of prostate cancer at our institution. Approximately 1% to 2% of patients with prostate cancer have hip prostheses. The presence of the prosthesis usually complicates the planning process because of dose perturbation around the prosthesis, radiation attenuation through the prosthesis, and the introduction of computed tomography artifacts in the planning volume. In addition, hip prostheses are typically made of materials of high atomic number, which add uncertainty to the dosimetry of the prostate and critical organs in the planning volume. When the prosthesis is bilateral, treatment planning is further complicated because only a limited number of beam angles can be used to avoid the prostheses. In this case study, we will report the observed advantages of using noncoplanar beams in the delivery of IMRT to a prostate cancer patient with bilateral hip prostheses. The ...
A method has been developed for calibration of CT-numbers to volumetric electron density distributions using tissue substitutes of known elemental composition and experimentally determined electron density. This information have been used in a dose calculation method based on photon and electron interaction processes. The method utilizes a convolution integral between the photon fluence matrix and dose distribution kernels. Inhomogeneous media are accounted for using the theorems of Fano and O'Connor for scaling dose distribution kernels in proportion to electron density. For clinical application of a calculated dose plan, a method for prediction of accelerator output have been developed. The methods gives the number of monitor units that has to be given to obtain a certain absorbed dose to a point inside an irregular, inhomogeneous object. The method for verification of dose distributions outlined in this study makes it possible to exclude the treatment related variance contributions, ...
It may be necessary to reduce microbiological contamination of crude drugs (medicinal plants or their parts like roots, leaves, flowers). This can be done by treating the drugs with ionizing radiation. Meethods for detection of such an irradiation were developed. It could be pointed out that measurements of luminescence, viscosity and electron spin resonance were suitable for specific drugs, but not for all drugs. (orig.).
With the advent of intensity-modulated radiation therapy (IMRT), the inclusion of heterogeneity corrections is further complicated by the conformal delivery of many small beams forming steep dose gradients. Radiation treatment planning has evolved to take into account even small changes in tissue density so that the dose to tumor can be further optimized. However, different treatment planning systems incorporate different heterogeneity correction algorithms, and it is unclear whether any of these algorithms are superior to others in terms of accurately predicting delivered radiation doses relative to measurement in a clinical setting. The purpose of this study was to determine the accuracy of heterogeneity dose calculations from two widely used IMRT treatment planning systems (Pinnacle and Corvus) against measurement. These two systems handle heterogeneity dose corrections by means of a collapsed-cone convolution superposition algorithm and a finite-size ...
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
BackgroundThere are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations....Full Text Available
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
When Silk fibre derived from Bombyx mori, a native biopolymer, was dissolved in highly concentrated neutral salts such as CaCl{sub 2}, the regenerated liquid silk, a gradually degraded peptide mixture of silk fibroin, could be obtained. The silk fibroin nanoparticles were prepared rapidly from the liquid silk by using water-miscible protonic and polar aprotonic organic solvents. The nanoparticles are insoluble but well dispersed and stable in aqueous solution and are globular particles with a range of 35-125 nm in diameter by means of TEM, SEM, AFM and laser sizer. Over one half of the {epsilon}-amino groups exist around the protein nanoparticles by using a trinitrobenzenesulfonic acid (TNBS) method. Raman spectra shows the tyrosine residues on the surface of the globules are more exposed than those on native silk fibers. The crystalline polymorph and conformation transition of the silk nanoparticles from random-coil and {alpha}-helix form (Silk I) into anti-parallel {beta}-sheet form ...
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
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
Microcapsules consisting of alginate and hyaluronic acid that can be decomposed by radiation are currently under development. In this study, the composition of the microcapsule material was optimized by changing the amounts of alginate and hyaluronic acid. Solutions of 0.025%, 0.05%, 0.1%, 0.2%, or 0.4% (wt./vol.) hyaluronic acid were mixed into a 0.2% alginate solution. To these mixtures, carboplatin (0.2 mmol) was added and the resulting material was used for the capsule preparation. The capsules were prepared by spraying the material into a CaCl{sub 2} solution (0.34 mol/l) using a microatomizer. These capsules were irradiated by a single dose of 2, 5, or 10 Gy {sup 60}Co {gamma}-ray radiation. Immediately after irradiation, the releasing of core content of microcapsule was determined, using a micro particle induced X-ray emission (PIXE) camera. The average diameter of the microcapsules was 22.3 {+-} 3.3 {mu}m, and that of the liquid core was 10.2 {+-} 4.3 {mu}m. The maximum ...
The effect of liquefied natural gas on pollutant emissions was evaluated experimentally with used and new appliances in the laboratory and with appliances installed in residences, targeting information gaps from previous studies. Burner selection targeted available technologies that are projected to comprise the majority of installed appliances over the next decade. Experiments were conducted on 13 cooktop sets, 12 ovens, 5 broiler burners, 5 storage water heaters, 4 forced air furnaces, 1 wall furnace, and 6 tankless water heaters. Air-free concentrations and fuel-based emission factors were determined for carbon monoxide, nitrogen oxides, nitrogen dioxide, and the number of (predominantly ultrafine) particles over complete burns?including transient effects (device warm-up and intermittent firing of burners) following ignition--and during more stable end-of-burn conditions. Formaldehyde was measured over multi-burn cycles. The baseline fuel ...
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).
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 ...
Current antidotal regimens for organophosphorus compound (OP) poisoning consist of a combination of pretreatment with a spontaneously reactivating AChE inhibitor such as pyridostigmine bromide, and postexposure therapy with anticholinergic drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent postexposure incapacitation, convulsions, performance deficits, or, in many cases, permanent brain damage (Dunn and Sidell, 1989). These problems stimulated the development of enzyme bioscavengers as a pretreatment to sequester highly toxic OPs before they reach their physiological targets. Several studies over the last two decades have demonstrated that exogenously administered human serum butyrylcholinesterase (Hu BChE) can be used successfully as a safe, efficacious, and single prophylactic treatment to ...
ObjectiveTo investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within...Full Text Available
SummaryConvection-enhanced delivery (CED) of substances within the human brain is becoming a more frequent experimental treatment option in the management of brain tumors, and...Full Text Available
PurposeA major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method...Full Text Available
Clinical applications of genetic therapies, including delivery of short, interfering RNAs (siRNAs) for RNA interference (RNAi), are limited due to the difficulty of delivering nucleic acids...Full Text Available
Objective: Pretargeting is the concept that combines optimal delivery of the antibody and rapid capture and elimination of the radioactivity. In this study, we evaluated the potential of antibody pretargeting to enable the tumor-targeting {sup 212}Pb for in vivo generation of {sup 212}Bi for {alpha} particle radiotherapy. Methods: The {sup 212}Pb/{sup 212}Bi chelate of DOTA-biotin, as well as their {gamma}-emitting analogues, {sup 203}Pb and {sup 205}Bi, was prepared and characterized. The radiolabeled compounds were injected in animals for evaluation of tumor targeting and normal tissue uptake and retention. In the pretargeting protocol, injection of 400 {mu}g of NR-LU-10 antibody-streptavidin conjugate was given at t=0 h, then 100 {mu}g of N-acetyl-galatosamine-biotin clearing agent was injected at t=20-24 h; finally, 1 {mu}g of {sup 212}Pb/{sup 212}Bi-DOTA-biotin was injected 6 h later. Results: Both {sup 203}Pb and {sup ...
The authors have studied the distribution of H-3 labelled schistosomicidal drug in mice by autoradiography. The H-3-labelled substances were found in liver and kidney and in successfully decreasing amounts in brain, lung, heart, fat, testis, pancreas and spleen. In various cells the silver granules were present mainly in the cytoplasms but a few in the nucleus. After administration of this labelled schistosomicidal drug, the mice were killed and studied in groups successively at 4, 8, 24 hrs. No difference in the distribution of silver granules were observed. This fact indicated that, this drug was rapidly absorbed and highly concentrated with a long duration of reservation in liver. All of these favours the schistosomicidal effect of the drug. As this drug was highly concentrated in the cytoplasm of liver cells, that might provide a pathophysiologic basis for the explanation of ...
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 ...
Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption.
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, ...
Stereotactic radiosurgery (SRS) precisely delivers high-dose radiation to a small target (usually less than 3-4 cm in diameter), in a single session with steep dose-fall, employing various radiation methods. SRS provides good tumor control for small brain metastases from various primary cancers, with minimal untoward effects on surrounding normal brain. This excellent tumor control prevents neurological death and maintains good activity of daily life. Although surgery with whole-brain radiation therapy (WBRT) remains an important option for patients with a solitary brain metastasis, SRS with or without WBRT should be considered in patients with a limited number of small tumors and a good prognosis. Many reports, as well as both retrospective and prospective reviews, have shown WBRT before or after SRS to improve local control and reduce new distant lesion emergence. However, upfront WBRT does not improve survival. There are two major delivery ...
The implementation of a three-dimensional conformal radiotherapy facility in the radiotherapy department of the Heinrich Heine University is described. Complex radiotherapy techniques with commercially available networked systems are introduced to improve clinical work. Over 18 month we have gained clinical experience with a PHILIPS Multileaf Collimator (MLC) mounted on a SL 25 linear accelerator. For a limited period the MLC was used as a conventional blocking device. The standard MLC-shapes are controlled with a stand-alone computer system. In addition, a three-dimensional treatment planning system (3-D-TPS / TMS-Radix, Helax AB) based on convolution/superposition algorithms was recently installed. Treatment optimization is achieved using static field arrangements with complete volumetric computerized tomographic patient data for 3-D-TPS. Conformal adaptation of the 95%-isodose to the Planning Target Volume (PTV, ICRU 50) results in MLC-field-shaping concerning ...
Parenting programmes are effective interventions for preventing and treating conduct problems in young children. Up to 20% of children in disadvantaged areas have conduct disorder. Recent government initiatives such as targeting early years services to designated disadvantaged Flying Start areas in Wales have resulted in increased nursery-care provision for pre-schoolers, yet little has been done to equip nursery staff with effective child behaviour management strategies. The purpose of this non-randomised trial platform study was to establish the feasibility of delivery and the effectiveness of the new Incredible Years Toddler Parent Programme in supporting nursery staff in managing difficult behaviour in the nursery. The Parent Programme is a 12-session (a two-hour session/week) course for carers/parents of children aged one to three years old, which encourages carers to: establish positive relationships with children through play and ...
Over the past 40 years, cavern storage of LPG's, petrochemicals, such as ethylene and propylene, and other petroleum products has increased dramatically. In 1991, the Gas Processors Association (GPA) lists the total U.S. underground storage capacity for LPG's and related products of approximately 519 million barrels (82.5 million cubic meters) in 1,122 separate caverns. Of this total, 70 are hard rock caverns and the remaining 1,052 are caverns in salt deposits. However, along the eastern seaboard of the U.S. and the Pacific northwest, salt deposits are not available and therefore, storage in hard rocks is required. Limited demand and high cost has prevented the construction of hard rock caverns in this country for a number of years. The storage of natural gas in mined caverns may prove technically feasible if the geology of the targeted market area is suitable; and economically feasible if the cost and convenience of service is competitive with ...
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
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
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (115) Inhalants (12) K Ketamine (1) L LSD ( ...
... 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 ( ...
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (112) Inhalants (12) K Ketamine (1) L LSD ( ...
... 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 ( ...
IntroductionResearch is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research...Full Text Available
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
A knowledge-based expert system has been developed to support human decision makers who assess drug products for inclusion in the Saskatchewan Formulary. Formulary inclusion and deletion decisions...Full Text Available
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
The main aim of the present study was to evaluate potential of ternary complexation (comprising of drug, cyclodextrin and polymer) as an approach for taste masking. For this purpose famotidine with...Full Text Available
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
Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,”...Full Text Available
Purpose of reviewPhysicians, researchers and policy makers must understand the myriad consequences of multidrug and extensively drug-resistant tuberculosis (TB) within...Full Text Available
Few data exist about the impact of computerized prescribing systems on outpatient medication errors (MEs) and adverse drug events (ADEs). We compared the rates of MEs and ADEs in handwritten sites versus...Full Text Available
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
Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available
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
SummaryEpigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies,...Full Text Available
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
ObjectivesWe undertook a meta-analysis to assess outcomes for drug-eluting (DES) and bare metal stents (BMS) in percutaneous coronary intervention (PCI) for unprotected...Full Text Available
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
Our understanding of the development of neurotransmitter systems in the central nervous system has increased greatly over the past three decades and it has become apparent that drug effects...Full Text Available
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
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
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
Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission...Full Text Available
...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...
... The pharmacologist/toxicologist and the statistician will jointly determine if a statistical review is needed and when the review should be done. ...
Objective: To find out safety and efficiency of Misoprostol in cervical ripening and induction of labour to achieve vaginal delivery. Results: From Misoprostol insertion to delivery time was 4-24 hours. Vaginal delivery was achieved in 80.2%, which included spontaneous, forceps and vacuum extraction. Caesarean section rate was 19.7%. Indications for C. Section included Misoprostol unresponsiveness 11% and fetal distress in 8.6%. Oxytocin augmentation was required in 32% of cases. Term babies were 58%. Intrauterine death and neonatal deaths were 9.8% and 8.6% respectively. Hyper stimulation and postpartum haemorrhage was seen in 2.4% and 3.7% of patients respectively. Conclusion: intravaginal Misoprostol is well tolerated and is very effective for the induction of labour in eclampsia. It helps vaginal delivery in toxemic patients, reduces maternal morbidity, mortality and hospital stay. (author)
The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery...Full Text Available
Autophagy is an evolutionarily conserved, catabolic process that involves the entrapment of cytoplasmic components within characteristic vesicles for their delivery to and degradation within lysosomes....Full Text Available
The purpose of this study is to explain the unplanned longitudinal dose modulations that appear in helical tomotherapy (HT) dose distributions in the presence of irregular patient breathing....Full Text Available
... and regional land, sea, air, and space-based systems, and ... means of delivery of weapons where such ... a separable and divisible part of the weapon. ...
BackgroundThe use of fractionated stereotactic radiotherapy (fsrt) has evolved with technical advances in noninvasive immobilization, radiation delivery, and image guidance....Full Text Available
SOME SCIENTISTS ALLEGE that exposure to electric and magnetic fields generated by electric power delivery systems is responsible for certain cancers (particularly among children), reproductive dysfunction,...Full Text Available
... 7 Page 11. Figure 5. Diffraction pattern shown a and ~ slip directions with the associated misalignment for single colonies of Ti6242 [2]. 8 Page 12. -- ...
Homidium bromide and isometamidium chloride are used extensively in the treatment of bovine trypanosomiasis in Africa, but no specific and sensitive method to detect the drug in plasma has been published yet. Comparing the methods of other investigators it was found that they could not overcome the protein binding of these drugs which reduced the available and determined drug to 10% of the real concentrations. These techniques overcome the protein binding by enzyme digestion and an alteration of the pH before adding the sample directly on clean-up columns. Drug recover rates above 80% were obtained. For the detection, the HPLC was employed using a C18 reversed phase analytical column and UV detection, determining both drugs as intact molecules. (author).
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...
The electroless nickel plating/poly(dl-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder dif...
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 ...
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 ...
Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, ...
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, ...
meyer r.m. & o’brien-pallas l.l. (2010)Nursing services delivery theory: an open system approach. Journal of Advanced Nursing66(12), 2828–2838.AimThis...Full Text Available
This document provides structural load requirements and their basis for maintaining the structural integrity of the Hanford Single-Shell Tanks during waste feed delivery and retrieval activities. The requirements are based on a review of previous requirements and their basis documents as well as load histories with particular emphasis on the proposed lead transfer feed tanks for the privatized vitrification plant.
A fuel injector comprises first and second housing parts, the first housing part being located within a bore or recess formed in the second housing part, the housing parts defining therebetween an inlet chamber, a delivery chamber axially spaced from the inlet chamber, and a filtration flow path interconnecting the inlet and delivery chambers to remove particulate contaminants from the flow of fuel therebetween.
A fluidic pump comprises a two-diode pump having a first displacement vessel, a third diode connected to receive output from the two-diode pump through a delivery line and discharge to an outlet, and a second displacement vessel connected to the delivery line. There is a feed tank at a greater height than the two-diode pump, and a drive unit for alternately pressurising and venting the first and second displacement vessels. The drive pressure required to operate the pump can be of the order of half that for a single stage 2-diode pump. (author).
There have been no radically new commercial bulk explosives since Atlas Powder Company's introduction of emulsions onto the market in 1968. But the effectiveness, safety and management of these familiar explosives is continuously being improved by the development of blast design techniques, explosives delivery and initiation systems, and monitoring methods. The author looks at developments in blasting technology and discusses experiences with Handibulk emulsion delivery systems.
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
We have studied the application of direct aperture optimization (DAO) as an inverse planning tool for breast IMRT. Additionally, we have analysed the impact of respiratory motion on the quality of the delivered dose distribution. From this analysis, we have developed guidelines for balancing the desire for a high-quality optimized plan with the need to create a plan that will not degrade significantly in the presence of respiratory motion. For a DAO optimized breast IMRT plan, the tangential fields incorporate a flash field to cover the range of respiratory motion. The inverse planning algorithm then optimizes the shapes and weights of additional segments that are delivered in combination with the open fields. IMRT plans were generated using DAO with the relative weights of the open segments varied from 0% to 95%. To assess the impact of breathing motion, the dose distribution for the optimized IMRT plan was recalculated with the isocentre sampled from a predefined distribution in a ...
Purpose/Objective: With the advent of computed tomography and magnetic resonance imaging, the three dimensional representation of the patient anatomy has become an invaluable resource for better diagnosis and delineation of the target volume and sensitive structures in radiation therapy. Although the therapeutic linear accelerator industry has made available highly sophisticated equipment, the aggressiveness in dose prescription and delivery has to be complimented by accurate dose computation methods. We have adopted a convolution/superposition algorithm for the calculation of absolute dose that fully accounts for the external shape and internal structure of the patient for photon treatment radiotherapy. In this paper, we will discuss the principles of the convolution algorithm and we will show how the computed dose compares to clinically relevant treatment techniques. Materials and Methods: A computer controlled data acquisition system and a ...
Limited demand and high cost has prevented the construction of hard rock caverns in this country for a number of years. The storage of natural gas in mined caverns may prove technically feasible if the geology of the targeted market area is suitable; and economically feasible if the cost and convenience of service is competitive with alternative available storage methods for peak supply requirements. It is believed that mined cavern storage can provide the advantages of high delivery rates and multiple fill-withdrawal cycles in areas where salt cavern storage is not possible. In this research project, PB-KBB merged advanced mining technologies and gas refrigeration techniques to develop conceptual designs and cost estimates to demonstrate the commercialization potential of the storage of refrigerated natural gas in hard rock caverns. Five regions of the U.S.A. were studied for underground storage development and PB-KBB reviewed the literature ...
The main aim of the project is to model the energy wood business and total logistics in a certain large region. First, wood utilisation locations inside this area are examined; the most important ones are the wood processing factories, and the heating- and power plants. After that, wood potentials in the forests of the area are evaluated in sub-areas suitable in size and sufficiently detailed for further evaluations. For that purpose, the most valuable source data are forest management plans, up to ten years forward, on which basis the wood fuel potentials can be evaluated following sustainable development. In Finland there are extensive and detailed data bases storing forest information and it is possible to collect necessary data for a data base applicable to our calculations. In logistical sense it is important to know, by which delivery chains the economically best and desired results are achieved. The software prototype based on data base is modelled and ...
The chemist and pharmacologist Fritz Hauschild developed the sympathomimetic agent Pervitin (metamphetamin) in the 1930s. Not only because of the abuse of the stimulant during the Second World War ("pilot's chocolate") it is one of the most controversial substances in drug history. Nearly forgotten are Hauschild's contributions to build up the drug system in the GDR. Although he was a convinced communist, the skilful pharmacologist gave very early warning of the imminent lack of innovation in the GDR pharmaceutical industry. A letter which he addressed to the Minister of Health, Max Sefrin (born 1913), did not lack explicitness. PMID:15997840
Based on the instrumental wavelength dispersive X-ray fluorescence technique of analysis (W D-X R F), the inorganic elements in four samples of commercial medicines drugs were analyzed. The samples were used without any chemical separation of the elements or chemical pre-treatment. Eleven elements could be identified, namely Si, P, S, Cl, K, Ca, Ti, Mn, Fe, Cu and Zn. However, Si, Ti and Mn have not been mentioned in the printed instructions for the use of the medicines drugs by the producers. (author)
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.
Flexible delivery reliability (FLP), which is in focus in this report, means that the customer shall be able to choose from a number of different grid tariffs of different qualities. This way he shows his actual willingness to pay for quality. It is an important difference compared with the KILE system, which is based on a surveyed willingness to pay. As it is planned to be implemented, FLP assumes that the customer must choose one of a number of different subscriptions and that he makes his choice based on his own preferences and costs what suits him best. The various subscribers entail different degrees of delivery reliability. For the grid companies, customers and regulatory authorities the FLP represents a challenge. It is assumed that the customers have a conscious attitude or preference with respect to delivery quality. That is not always the case today.
We present two cases of fetal neck masses that were initially diagnosed by ultrasound and further evaluated with prenatal MRI. MRI findings aided in further delineating the neck masses, increasing confidence in the final diagnosis (cervical teratoma and cystic hygroma). With the fetal airway typically filled with fluid that is of high signal on T2-weighted sequences, MRI images in three planes could identify whether the fetal larynx and trachea were partially or completely compressed by the neck tumor. This information was particularly useful in determining if a controlled delivery such as ex utero intrapartum treatment (EXIT) was necessary and aided the surgeons in planning their approach to establishing airway control in the delivery room. (orig.)
Abstract While the techniques and technologies associated with contaminated sediment remediation are relatively mature, there are several issues associated with these practices that make them unattractive. The inability of currently used mechanical mixing implements to place amendments in aqueous environments and their intrusive behavior toward benthic communities are just two examples of a necessity for an improved delivery method. Waterjets may be a viable option for placement of particulate remediation amendments, such as activated carbon and granular iron, at depth. A custom waterjet nozzle and injection system has been fabricated by the authors to examine this delivery concept. The developed injection system's performance was tested by characterizing the waterjet-delivered amendment (...
A variable gene delivery system has been developed based on conjugating chitosan to biotin through a functionalized poly(ethylene glycol) (PEG) spacer, which can be used to further bind different molecules on the outer layer of a polymer/DNA complex by streptavidin (SA)-biotin linkage. In this study, TAT-conjugated SA was used as the model molecule to prove the conjugation function of the prepared complex. In addition, low-molecular-weight poly(ethyleneimine) (PEI) was added into the polymer/DNA complex to increase the transfection efficiency. The results of the luciferase assay show that the transfection efficiency of the prepared complex was significantly correlated with the amount of PEI and was further enhanced when TAT was conjugated to the complex by SA-biotin linkage. Considered to have negligible cytotoxic effects, the variable gene delivery complex prepared in this study would be of considerable potential as carriers for in vitro ...
from a broad range of sources including industrial and consumer products, food additives and drugs that never made it to the market to evaluate the predictive toxicity...
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
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
BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial...Full Text Available
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...
Abstract Evaluation of pharmaceutical agents in children is now conducted earlier in the drug development process. An important consideration for this pediatric use is how to assess and support its safety. This article is a collaborative effort of industry toxicologists to review strategies, challenges, and current practice regarding preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals. Biopharmaceuticals include a diverse group of molecular, cell-based or gene therapeutics derived from biological sources or complex biotechnological processes. The principles of preclinical support of pediatric drug development for biopharmaceuticals are similar to those for small molecule pharmaceuticals and in general follow the same regulatory guidances outlined by...
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 ...
After fluid resuscitation, vasoactive drug treatment represents the major cornerstone for correcting any major impairment of the circulation. However, debate still rages as to the choice of agent, dose,...Full Text Available
PurposeTo identify the extent of persistence (period of time of continuous therapy with the drug prescribed) of glaucoma patients treated with prostaglandins (latanoprost, bimatoprost,...Full Text Available
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
Monitoring describes the prospective supervision, observation, and testing of an ongoing process. The result of monitoring provides reassurance that the goal has been or will be achieved, or suggests...Full Text Available
BACKGROUNDNew diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,...Full Text Available
Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide...Full Text Available
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
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
Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications...Full Text Available
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
ObjectiveEpidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and...Full Text Available
... is reduced: 1) by lack of oxygen, 2) in hypercapnia associated with closed rooms or tents, 3) by use of sleeping drugs, antipyretics, insulin, and 4 ...
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
RationaleProcedures for studying the effects of medications on satiation will assist the development of obesity medications.ObjectivesFull Text Available
Patient decision support systems have a promising role in the delivery of health care. However, the best approach for further development of these systems is a matter of speculation. To help chart a...Full Text Available
Purpose: The authors have developed a novel technique using an electronic portal imaging device (EPID) to verify the geometrical accuracy of delivery of dose-rate-regulated tracking (DRRT)....Full Text Available
Personal Health Records (PHRs) are increasingly recognized as a strategy to improve patient-provider communication, availability of health information, and quality of care, by making the delivery of...Full Text Available
Tension pneumothorax in newborns is a rare but life-threatening complication. We encountered a case of a full-term neonate with a breech presentation. An elective cesarean section was scheduled. Immediately...Full Text Available
Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning...Full Text Available
BackgroundThere is a strong inverse relationship between final vessel diameter and subsequent risk of treatment failure after coronary stent deployment. The aim of this study was...Full Text Available
BackgroundSilica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential...Full Text Available
Effective small interfering RNA (siRNA)–mediated therapeutics require the siRNA to be delivered into the cellular RNA-induced silencing complex (RISC). Quantitative information of this essential...Full Text Available
Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy. One key component of 4D radiotherapy planning...Full Text Available
Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity...Full Text Available
Craniofacial injuries require a variety of different cell types to repopulate areas of bone, cartilage, tendon, and fat. Mesenchymal stem cells (MSCs) provide a multipotent cell source for tissue...Full Text Available
Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy...Full Text Available
ObjectiveTo investigate the effect of maternal obesity on mode of delivery following induction of labour (IOL) for prolonged pregnancy and subsequent intrapartum and neonatal complications.DesignRetrospective...Full Text Available
BackgroundMother-to-Child Transmission (MTCT) of HIV remains the main mode of acquisition of HIV in children. Transmission of HIV may occur during pregnancy, delivery or breastfeeding....Full Text Available
Previous studies have documented diagnostic bias and noted that its reduction could eliminate misdiagnosis and improve mental health service delivery. Few studies have investigated clinicians'...Full Text Available
Tendon reconstruction using grafts often results in adhesions that limit joint flexion. These adhesions are precipitated by inflammation, fibrosis, and paucity of tendon differentiation signals...Full Text Available
Over the last several years, as cesarean deliveries have grown increasingly common, there has been a great deal of public and professional interest in the phenomenon of women ‘choosing’...Full Text Available
The delivery of proteins and organelles to the vacuole by autophagy involves membrane rearrangements that result in the formation of large vesicles called autophagosomes. The mechanism underlying autophagosome...Full Text Available
BackgroundThere has been increasing interest in the ability of the internet to produce behaviour change. The focus of this study was to describe program exposure across three intervention...Full Text Available
The temporal fine structure (TFS) of sound contributes significantly to the perception of music and speech in noise. The evaluation of new strategies to improve TFS delivery in cochlear implants (CIs)...Full Text Available
BACKGROUND AND AIMS:In view of increasing therapeutic efficacy, the delivery of hepatitis C virus (HCV) antiviral treatment is expected to increase. Yet practical experience reveals...Full Text Available
Spontaneous rupture of membranes (ROM) is a normal component of labor and delivery. Premature ROM (PROM) refers to rupture of the fetal membranes prior to the onset of labor irrespective of gestational...Full Text Available
BackgroundPolyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene...Full Text Available
PURPOSE:Two different regimens of SWL delivery for treating urinary stones were compared.METHODS:Patients with urinary stones were randomly divided...Full Text Available
Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus...Full Text Available
Scoping studies have been used across a range of disciplines for a wide variety of purposes. However, their value is increasingly limited by a lack of definition and clarity of purpose. The UK's Service...Full Text Available
Study of the conversion of chicken litter to biogas for the production of energy. There was an additional requirement that after extracting the energy from the chicken litter the nutrient value of the raw chicken litter had to be returned to the Ak-Chin Farms for use as fertilizer in a form and delivery method acceptable to the Farm.
In many radiotherapy clinics, geometric uncertainties in the delivery of 3D conformal radiation therapy and intensity modulated radiation therapy of the prostate are reduced by aligning the...Full Text Available
Globalization and technological innovation are creating dynamic networks or chains of interconnected players, often known as value delivery networks or supply chains, in which a firm, whether manufacturing or service, holds the key to creating and delivering value in the form of offerings to the customers. This idea of value creation and exchange is the foundation stone of relationship marketing and it is considered successful when closeness is said to have been established in the relationship which subsequently leads toward the achievement of objectives. In order to study and understand the creation of value through relationship closeness in a value delivery network particularly at the backward end, a literature review is conducted. A framework is further developed with the help of Interp...
More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting...Full Text Available
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
Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between...Full Text Available
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).
The heterogeneous solid catalyst, mercaptopropylsilica (MPS), has been prepared by a modified procedure in water and its structure confirmed by solid state carbon-13 CP-MAS NMR spectrum. This catalyst has been efficiently utilized for the synthesis of a wide variety of tri-, tetrasubstituted imidazoles and their bis-analogues at room temperature. The protocol was further explored for the synthesis of the drug trifenagrel.
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.
BackgroundAs the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images...Full Text Available
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.)
In this study the development of a methodology to detect illicit drugs and plastic explosives is described with the objective of being applied in the realm of public security. For this end, non-destructive assay with neutrons was used and the technique applied was the real time neutron radiography together with computerized tomography. The system is endowed with automatic responses based upon the application of an artificial intelligence technique. In previous tests using real samples, the system proved capable of identifying 97% of the inspected materials.
1 The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37 degrees C. 2 Acute renal failure...Full Text Available
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
BackgroundNo consensus evidence-based guidelines for the routine laboratory monitoring of children with JIA receiving non-steroidal anti-inflammatory drugs (NSAIDs) exist. The purpose...Full Text Available
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
The two-compartment radioassay for microbial kinetics based on continuous measurement of the {sup 14}CO{sub 2} released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial {sup 14}CO{sub 2} liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and ...
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
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
In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available
Computational fluid dynamics(CFD) code FLUENT was used to simulate the thermal hydraulic processes occurring in conceptual design of the accelerator-driven subcritical reactor(ADSR) liquid lead target. The purpose of the analysis is to investigate the thermal hydraulic characteristics of liquid lead as ADSR target material with various target geometries and injection locations of proton beam. In the calculation analysis, the local temperature of the liquid lead target rises to the boiling temperature very rapidly. When the proton beam is injected from the bottom of the target system, the duration time to reach the boiling temperature is longer and the temperature distribution is flatter than other cases.
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...
In an effort to develop octahedral metal complexes as chemotherapeutic and diagnostic agents targeted to DNA, it is critical to optimize the properties of their cellular uptake. Appending d-octaarginine...Full Text Available
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.
... L. Sutton. 2000. Is the aquatic weed hygrophila, Hygrophila polysperma (Polemoniales: Acanthaceae), a suitable target for classical biological ... ...
Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...
By W. Wayne Scott. Langley Research Center. SUMMARY. Thin- and thick-target bremsstrahlung spectra are presented for electron energies up to 7.0 MeV. ...
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 ...
...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 ...
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 ...
A qualitative method, involving supported liquid?liquid extraction (SLE) and ultra high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS?MS), was developed for the rapid tentative identification of various drugs of abuse in urine. In this study, 28 drugs and metabolites were covered by the screening procedure. Before analysis, urine samples were extracted by SLE and good extraction recoveries were obtained for most investigated compounds. The UHPLC strategy was then selected for the rapid separation of amphetamines, cocaine, opiates and related compounds in urine. Using columns packed with sub-2??m particles, analysis time was reduced down to 2?min, while maintaining acceptable performance. Finally, the detection was by tandem MS operating in the single reaction...
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...
The objective of this study was to examine the effect of a nonsteroidal anti-inflammatory drug (NSAID) plaster for knee osteoarthritis among Japanese patients. An open-labeled, randomized, controlled, multiclinic trial was performed involving outpatient clinic groups. Two comparative groups?plaster NSAIDs and oral NSAIDs?were randomly allocated. The drugs used were limited to the current top three in both groups in Japan. Treatments were assessed after four?weeks and compared with the baseline scores. Outcomes were evaluated by two psychometric measures: Japanese knee osteoarthritis measure, and pain with the visual analogue scale. The total number of patients included in the final evaluation was 165 (87 for the plaster group and 78 for the oral group). Between these two groups there were ...
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...
The aim of this study is to evaluate the specificities of the irradiation of drugs in frozen aqueous solution. The structures of the degradation products were determined to gain insight into the radiolysis mechanisms occurring in frozen aqueous solutions. Metoclopramide hydrochloride and metoprolol tartrate were chosen as models. The frozen solutions were irradiated at dry ice temperature by high energy electrons at various doses. The drug purity (chemical potency) and the radiolysis products were quantified by HPLC-DAD. Characterization of the degradation products was performed by LC-APCI-MS-MS. The structures of the radiolysis products detected in irradiated frozen aqueous solutions were compared to those detected in solid-state and aqueous solutions (previous studies). For both metoclop...
Purpose: The purpose of this course is to review the physical principles underlying design, clinical application and execution of interstitial and intracavitary implants in the classical low dose-rate (LDR) range. This year, the course will focus on quality assurance of sources, applicators and treatment planning software. In addition, development of procedures and QA checks designed optimize treatment delivery accuracy and patient safety during each individual procedure will be reviewed. The level of presentation will be designed to accommodate both physicists and physicians. Implementation of recently published AAPM Task Group reports (no. 40, 'Comprehensive Quality Assurance' and No. 43, 'Dosimetry of Interstitial Brachytherapy Sources') will be reviewed. Outline: (A) General Principles (1) QA endpoints: temporal accuracy, positional accuracy, dose delivery accuracy, and safety of the patient, personnel, and the institution (2) QA procedure ...
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)
In the CERN approach to the design of a neutrino factory, the repetition frequency of the proton beam is high enough to consider stationary solid targets as a viable solution for multi-MW beams. The target consists of high density tantalum spheres of 2 mm diameter which can efficiently be cooled by passing a high mass flow He-gas stream through the voids between the Ta-granules. Very small thermal shocks and stresses will arise in this fine grained structure due to the relatively long burst of 3.3 ms from the SPL-proton linac. In a quadruple target system where each target receives only one quarter of the total beam power of 4 MW, conservative temperature levels and adequate lifetimes of the target are estimated in its very high radiation environment. A conceptual design of the integration of the target into the magnetic horn-pion-collector is presented.
RADIANT{trademark} is manufactured by United States Surgical Corporation, Vascular Therapies Division, (formerly Progressive Angioplasty Systems). The system comprises a liquid {beta}-radiation source, a shielded isolation/transfer device (ISAT), modified over-the-wire or rapid exchange delivery balloons, and accessory kits. The liquid {beta}-source is Rhenium-188 in the form of sodium perrhenate (NaReO{sub 4}), Rhenium-188 is primarily a {beta}-emitter with a physical half-life of 17.0 hours. The maximum energy of the {beta}-particles is 2.1 MeV. The source is produced daily in the nuclear pharmacy hot lab by eluting a Tungsten-188/Rhenium-188 generator manufactured by Oak Ridge National Laboratory (ORNL). Using anion exchange columns and Millipore filters the effluent is concentrated to approximately 100 mCi/ml, calibrated, and loaded into the (ISAT) which is subsequently transported to the cardiac catheterization laboratory. The delivery ...
Dose reconstruction is a process that re-creates the treatment-time dose deposited in a patient provided there is knowledge of the delivered energy fluence and the patient's anatomy at the time of treatment. A method for reconstructing dose is presented. The process starts with delivery verification, in which the incident energy fluence from a treatment is computed using the exit detector signal and a transfer matrix to convert the detector signal to energy fluence. With the verified energy fluence and a CT image of the patient in the treatment position, the treatment-time dose distribution is computed using any model-based algorithm such as convolution/superposition or Monte Carlo. The accuracy of dose reconstruction and the ability of the process to reveal delivery errors are presented. Regarding accuracy, a reconstructed dose distribution was compared with a measured film distribution for a simulated breast treatment carried out on a thorax ...
Cell-penetrating peptides (CPPs) are useful tools for the delivery of hydrophilic bioactive molecules, such as peptides, proteins, and oligonucleotides, across the cell membrane. To realize the delivery of therapeutic macromolecules by CPPs, the CPPs are required to show resistance to protease and no cytotoxicity. In order to produce potent non-toxic and protease-resistant CPPs with high cellular uptake, we designed an amphipathic helix peptide using ?-aminoisobutyric acid (Aib, U) and named it MAP(Aib). In the MAP(Aib) molecule, five Aib residues are aligned on the hydrophobic face of the helix and five lysine (K) residues are aligned on the hydrophilic face. MAP(Aib) showed potent resistance to trypsin and pronase compared with MAP, an amphipathic helix peptide formed by usual amino acids. Fluorescein-labeled MAP(Aib) efficiently traversed the A549 cell membrane, diffusing into the cytoplasm and slightly into the nucleus without exerting any ...
... 4. Military Working Dogs iMWDs). As used in this Instruction refers to drug detector dogs only. 5. Military Working Doq Executive Agent M(WJDEMA. ...
Background:The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who...Full Text Available
The study involved 110 randomly selected dairy farms located in the Ontario, Canada counties of Bruce, Grey, Huron, Oxford, Perth, Waterloo and Wellington. Herds were classified as "intensive" and "extensive"....Full Text Available
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
BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available
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
The present study discusses the contribution of the adoption of more rigorous and objective criteria to the selection and analysis of information sources, leading to more scientific rigour when registering phytotherapic drugs. To this end, it is herein proposed the adoption of a previously tested and acknowledged methodology, namely the Systematic Revision, as a standard for phytotherapic drug analyses. In order to show differences brought about by the Systematic Revision during the registration procedures of phytotherapic drugs, the case of the Maytenus ilicifolia (known popularly in Brazil as 'espinheira-santa') is presented. As it is well known, the use of ionizing radiation is expanding, especially in medicine and pharmacy. Therefore, gamma radiation was applied to the microbiological quality control of phytotherapic matrices. Results indicated a positive contribution of Systematic Revision to the ...
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
Objective:This article examines relationships between reproductive onset and lifetime history of smoking, regular smoking, and nicotine dependence, and cannabis and other illicit...Full Text Available
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
BackgroundRifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month...Full Text Available
SummaryBackgroundThe US FDA has been collecting information on medical devices involved in significant adverse advents since 1984. These reports have...Full Text Available
The safety, pharmacokinetics, and distribution in tissue of an amphotericin B (AmB)-cholesteryl sulfate colloidal dispersion (ABCD) were compared with those of micellar amphotericin B-deoxycholate (m-AmB)....Full Text Available
IntroductionRecent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers’...Full Text Available
Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous...Full Text Available
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 ...
The juxtacapsular BNST (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of...Full Text Available
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
Treatment of functional bowel disorders of irritable bowel-type (IBS) in children remains a difficult task because of a lack of drugs with low adverse event profile. We here report the results of a...Full Text Available
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
Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms. The aim of present study was to prepare...Full Text Available
The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years)...Full Text Available
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
Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it...Full Text Available
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
Opioids have been regarded for millennia as among the most effective drugs for the treatment of pain. Their use in the management of acute severe pain and chronic pain related to advanced medical...Full Text Available
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
Telbivudine is a novel nucleoside drug recently approved for the treatment of patients with chronic hepatitis B. Its nonclinical safety was evaluated in a comprehensive program of studies, including...Full Text Available
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
AimsThe efficacy of topical glucocorticosteroids in rhinitis and asthma is likely to depend on drug retention in the airway mucosa. With fluticasone propionate, retention may be...Full Text Available
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
BackgroundThe precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying...Full Text Available
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
Integration of solid-state biosensors and lipid bilayer membranes is important for membrane protein research and drug discovery. In these sensors, it is critical that the solid-state sensing...Full Text Available
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
BackgroundArtemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries,...Full Text Available
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
Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug...Full Text Available
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
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor...Full Text Available
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
The development of azole resistance in Candida albicans is most problematic in patients with AIDS who receive long courses of drug for therapy or prevention of oral candidiasis. Recently,...Full Text Available
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
The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available
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
African trypanosomes exert significant morbidity and mortality in man and livestock. Only a few drugs are available for the treatment of trypanosome infections and therefore, the development of new...Full Text Available
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
ObjectiveTo evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in...Full Text Available
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
Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed. (orig.)
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
Abstract Objective: This study aims to gain an overview of hot topics related to research focused on Chinese herbal drugs by authors inside China and outside of China in the past 10 years. Methods: PubMed/MEDLINE was utilized in order to investigate and select research that was published on ?Chinese herbal drugs?? from 1998 to 2007, by authors located both inside and outside of China (MeSH terms were downloaded and ranked). MeSH terms that frequently appeared were identified and co-word analysis was carried out for two groups: (1) authors located in China, and (2) authors based outside of China, respectively. The hot topics concerning research into Chinese herbal drugs were concluded after cluster analysis and related document analysis. Results: For authors in the China group versus those ...
Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment...Full Text Available
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 ...
Ayurvedic drugs have begun to be evaluated in controlled clinical trials. The trials, often placebo controlled, are usually designed to demonstrate superiority. Though the results have been usually...Full Text Available
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
Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been...Full Text Available
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
During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma...Full Text Available
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...
Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular...Full Text Available
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
The hepatic uptake rate for certain albumin-bound drugs and metabolites correlates poorly with their equilibrium unbound concentration in the plasma, suggesting that binding equilibrium may not always...Full Text Available
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
BackgroundWebsites of many rogue sellers of medications are accessible through links in email spam messages or via web search engines. This study examined...Full Text Available
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 ...
BackgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence...Full Text Available
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
1 The plasma protein binding of theophylline was determined after addition of [14C]-theophylline (15 micrograms/ml) to plasma from 24 healthy drug-free volunteers and equilibrium dialysis for 2 h at...Full Text Available
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
Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop...Full Text Available
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
Mechanism-based inhibition of cytochrome P450 (CYP) 3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive...Full Text Available
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
Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha...Full Text Available
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...
Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM). In the past, clinical data showed that some herbs possessed anticancer properties,...Full Text Available
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
Objectives:The aim of this study was to analyze clinical records of dental patients attending the Dental Department at the University of Jordan Hospital: a teaching hospital in Jordan....Full Text Available
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
Two field-adapted colorimetric methods for measuring the antimalarial drug chloroquine in urine are described. Both are modifications of the method of Saker and Solomons for screening urine for phencyclidine...Full Text Available
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
BackgroundThe default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention...Full Text Available
AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent...Full Text Available
Plumbagin is found in many herbal plants and inhibits the growth of various bacteria. Escherichia coli strains are relatively resistant to this drug. The mechanism of resistance is...Full Text Available
BackgroundA relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with...Full Text Available
Background:With the advent of newer antipsychotic drugs, side effects such as sexual dysfunction have been a major contributor toward treatment compliance. There are only...Full Text Available
This study examines the longitudinal relationship between personal and sexual partner incarceration and subsequent HIV risk behaviors among drug-involved men and their primary female sexual...Full Text Available
...1) A privately owned motor vehicle. (2) A privately owned boat. (3) An indigenous animal, military working dog, or guide dog for the blind or visually-impaired accompanying its owner. (4) A narcotic or dangerous drug or...
Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25-250 g/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants. Copyright Copyright 2009 John Wiley & Sons, Ltd.
This paper describes new strategies for the brain-specific delivery of radionuclides that can be used to evaluate regional cerebral perfusion by single photon imaging techniques. A description of several examples of interesting new strategies that have recently been reported is presented. A new approach at this institution for the brain-specific delivery of radioiodinated iodophenylalkyl-substituted dihyronicotinamide systems is described which shows good brain uptake and retention in preliminary studies in rats. Following transport into the brain these agents appear to undergo facile intracerebral oxidation to the quaternized analogues which do not recross the intact blood-brain barrier and so are effectively trapped in the brain. 49 refs., 9 figs., 1 tab.
The goals of this paper are to describe new strategies being pursued at several institutions for the brain-specific delivery of radionuclides that can be used to evaluate regional cerebral perfusion by single photon imaging techniques. A comprehensive review of the literature is beyond the scope of these proceedings and our goal is to, therefore, present a description of several examples of interesting new strategies that have recently been reported. In addition, the authors also describe a new approach being pursued at their institution for the brain-specific delivery of radioiodinated iodophenylaklyl-substituted dihydronicotiamide systems which shows good brain uptake and retention in preliminary studies in rats. Following transport into the brain these agents appear to undergo facile intracerebral oxidation to the quaternized analogues which do not cross the intact blood-brain-barrier and are effectively trapped in the brain.
This paper addresses the problem of partitioning a local service region into nonoverlapping work areas in which pickups and deliveries are made throughout the day. For a fleet of homogeneous vehicles, a given set of customers, and expected demand for service, the objective is to find the least number of work areas or clusters that satisfy a variety of geometric and capacity constraints. Using rectangles as the basic shape, each cluster must have an aspect ratio that falls within certain bounds, as well as meet load and time requirements dictated by the capacity of a vehicle and the working hours in a day, respectively. The latter requirement presents a unique hurdle because travel times are a function of the actual routes followed by the drivers, and are not known, even in a probabilistic ...
To mitigate damages caused by agricultural runoff, private lake owners' associations are paying for inlake and instream pollution abatement measures and on land-conservation practices. This phenomenon supports the notion that individuals who benefit from improved water quality should be willing to pay part of the abatement costs. The research suggests that on land-conservation measures can substantially reduce sediment delivery at low cost. The Sediment Economics (SEDEC) model was modified and then used to select and to site management systems that achieved stated sediment goals at least cost. Other resource policies such as T value, no-till, and contouring were compared with the least-cost frontier and shown to be more costly. The noncropland areas substantially reduced sediment delivery to water channels and lowered abatement costs. Further research is needed for long-range watershed-planning models such as SEDEC.
The need to evolve with our ever-changing student bodies has never been as great as it is today, particularly given the advanced technological aptitude of today's students. This retrospective study evaluates student outcomes as they relate to overall course score and composite quiz and examination scores from a basic pharmacology course taught over three separate semesters using three different lecture delivery modalities: traditional in-class; blended; and online-only. A total of 48 students from a US university's health sciences bachelor degree programme enrolled in one of these three sections between 2009 and 2010. A one-way analysis of variance test with Tukey's honestly significant difference post hoc testing was utilized to determine if any statistical difference existed between the ...
Abstract The purpose of this study was to compare the HL 20 roller pump (Jostra USA, Austin, TX, USA) and Rotaflow centrifugal pump (Jostra USA) on hemodynamic energy production and gaseous microemboli (GME) delivery in a simulated neonatal cardiopulmonary bypass (CPB) circuit under nonpulsatile perfusion. This study employed a simulated model of the pediatric CPB including a Jostra HL 20 heart lung machine (or a Rotaflow centrifugal pump), a Capiox BabyRX05 oxygenator (Terumo Corporation, Tokyo, Japan), a Capiox pediatric arterial filter (Terumo Corporation), and inch tubing. The total volume of the experimental system was 700 mL (500 mL for the circuit and 200 mL for the pseudo neonatal patient). The hematocrit was maintained at 30% using human blood. At the beginning of each trial, a 5 ...
Transmission Control Protocol (TCP) provides mechanisms for reliable data communications. Although it works well in wired networks, it fails to offer satisfactory performance in lossy and wireless environments. And in the multi-hop wireless infrastructure, packet delivery suffers high cumulative loss rate if traveling over multiple wireless hops. The Selective acknowledgment (SACK) is one header option that might be used to combat segment corruptions in air channels. In this paper, an alternative set of flow control mechanisms is proposed to handle high packet loss rate in a wireless medium. Using a measurement-based mechanism, sustainable segment delivery is achievable through a novel size-reduction method. Multiple segment retransmission mechanisms are introduced to reduce successive tim...
BACKGROUND: It was previously reported that dendrosomes, i.e. neutral, biodegradable, covalent or self-assembled, hyperbranched, spheroidal nano-particles with a size ranging from 15 to 100 nm, provide a convenient and efficient means of gene delivery into various kinds of cells such as human hepatoma and kidney cells as well as animal models.RESULTS: New studies via circular dichroism show that hydrophilic and amphipathic dendrosomes either do not affect the DNA structure or moderately transform it from B- to A-conformation. Gene delivery into human liver, kidney, and endothelial cells as well as other animal cells like Bowes, U-937, Raw, CCRF-CEM, MOLT-4, K562, Huh-7 and VERO reveal that the genes are efficiently expressed and in comparison with other gene porters like Lipofectin or bact...
The role of radiation therapy in local tumor control and decreased incidence of pulmonary metastasis is reported in 271 patients who were entered into the Intergroup Ewing's Sarcoma Study with more than one year follow-up and on whom all radiotherapy records were reviewed. The majority of the patients were irradiated to the primary tumor with doses of 4500 to 6500 rad in five to six weeks in combination with systemic administration of three drugs (vincristine, actinomycin-D and cyclophosphamide) or four drugs (vincristine, actinomycin-D, cyclophosphamide and adriamycin). One of the groups of patients was treated with three drugs and bilateral pulmonary irradiation (1500 rad, uncorrected dose, in two weeks). Preliminary analysis shows an overall local primary tumor control of 89%. Patients with lesions in the pelvis had a local failure rate of 17% (9 of 52) and in the humerus 23% (7 of 31). Factors affecting local ...
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By the year 2000, the Postal Service aims to reduce its diesel transport by around 15000 vehicles. The advisory service, Detecon, is reviewing alternatives for postal deliveries as part of the ''Post 2000'' initiative. One such system is an electric-powered vehicle with a zinc-air battery from the Israeli firm Electric Fluid Limited (EFL). (orig.)
In this note we describe a conceptual design of a part ofthe electron beam delivery system for FERMI@Elettra free electron laser(FEL) located between the end of the linac and the entrance to the FEL.This part includes the emittance diagnostic section, the electron beamswitchyard for two FELs called spreader and matching sections. The designmeets various constrains imposed by the existing and planned buildingboundaries, desire for utilization of existing equipment and demands forvarious diagnostic instruments.
BackgroundSouth Africa has a high tuberculosis (TB)-human immunodeficiency virus (HIV) coinfection rate of 73%, yet only 46% of TB patients are tested for HIV. To date, relatively...Full Text Available
The requirements of high-pressure compressors increase. The customers wish still larger quantities of delivery with smaller employment of achievement, minimal oil consumption, service amenability, long intervals of maintenance and so forth. For this, the author of the contribution under consideration presents two series of modular developed high-pressure compressors in compact design for industrial air and technical gases which exactly fulfil these requirements.
The Training Department at the Point Lepreau GS has been developing and improving its training for technical support staff. A generic set of objectives are being used as the basis for a systematic approach to training. The program covers general and job specific knowledge and skills using a mix of classroom instruction, mentoring and continuing training seminars. This paper describes experience, success and the challenges in the development, delivery and evaluation of the training program. (author)
Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS)...Full Text Available
Spark ignition internal combustion engines perform satisfactorily when the fueled with biomass producer gas from a fluidized bed gasifier. Although power output is reduced compared to natural gas levels, full power recovery can be achieved with a relatively low level of supercharging. Important considerations are an adequate fuel delivery system and adquate gas cleaning. ref.
Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable...Full Text Available
...j-3/j-3311/DLAD/rev5.htm ), and MIL-STD-2073-1, Standard Practice for Military Packaging (and...Guidelines will comply with DLAD 47.305-1, and MIL-STD-2073-1. (f) Delays in delivery caused by...
PurposeWe conducted a comparative study of Clinical Target Volume (CTV) definition of pelvic lymph nodes by multiple GU radiation oncologists looking at the levels...Full Text Available
The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I...Full Text Available
The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large...Full Text Available
The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles...Full Text Available
... detected (and reported) as a by-product of MRM screening (MS/MS) targeted by Law or Rule ... detected (and reported) as a by-product of MRM screening (MS/MS) targeted by Law or Rule ...
Many genetic processes depend on proteins interacting with specific sequences on DNA. Despite the large excess of nonspecific DNA in the cell, proteins can locate their targets rapidly. After initial...Full Text Available
Peroxisomes, glyoxysomes, glycosomes, and hydrogenosomes have each been classified as microbodies, i.e., subcellular organelles with an electron-dense matrix that is bound by a single membrane. We investigated...Full Text Available
Considering accessibility of the 3′UTR is believed to increase the precision of microRNA target predictions. We show that, contrary to common belief, ranking by the hybridization energy or by...Full Text Available
Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available
Operant conditioning techniques were applied to the study of how target fixations are controlled by the probability of signal occurrence. In a standard vigilance setting, gaze at three illuminable...Full Text Available
Cytokinesis in animal and fungal cells utilizes a contractile actomyosin ring (AMR). However, how myosin II is targeted to the division site and promotes AMR assembly, and how the AMR coordinates with...Full Text Available
Purposes1. To determine the optimal pelvic nodal clinical target volume for post-operative treatment of endometrial cancer. 2. To compare the DVH of different treatment planning...Full Text Available
... they assisted in the 2000 attack on the USS Cole? ... List the types of targets that ETA has attacked. ... was at least partially responsible for the attack. ...
... Tanzania, and the attack on the USS COLE. ... vis another has no bearing on the legality of the attack. If the person attacked is a combatant, the use of ...
The production of polarized negative ion beams by collisional pumping is described. Collisional pumping utilizes repeated charge changing collisions in a thick electron-spin-polarized gas or vapor target to form a polarized fast atom beam. The polarized fast atom beam is then partially converted into a polarized negative ion beam in a vapor target. Analysis is presented for a hydrogen beam passing through either a thick polarized H atom target or a thick polarized alkali target. Large polarizations and large currents may be possible.
The production of polarized negative ion beams by ''collisional pumping'' is described. Collisional pumping utilizes repeated charge changing collisions in a thick electron-spin-polarized gas or vapor target to form a polarized fast atom beam. The polarized fast atom beam is then partially converted into a polarized negative ion beam in a vapor target. Analysis is presented for a hydrogen beam passing through either a thick polarized H atom target or a thick polarized alkali target. Large polarizations and large currents may be possible.
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.
This paper present the results of a series of calculations made to determine the "2"3"8Pu production potential of several advanced target assembly designs in the Fast Flux Test Facility (FFTF). These calculations show that by using advanced target designs the intimately mix the "2"3"7Np target material with an yttrium hydride moderator, the FFTF has the potential of producing up to 30 kg of high-quality "2"3"8Pu per year.
BackgroundXMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.ResultsWe extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine), AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also block XMRV infection with comparable efficacy in vitro. Our data ...
This paper is a progress report on the role of radiation therapy (RT) in local tumor control and the decreased incidence of pulmonary metastasis in 251 patients entered in the Intergroup Ewing's Sarcoma Study. All were followed for more that 1 year, and their RT records were reviewed. Doses to the primary tumor in the range of 4,500--6,500 rad were administered over approximately 5 to 6 weeks in combination with 4 drugs, i.e., vincristine (VCR), dactinomycin (DAC), cyclophosphamide (CY), and adriamycin, or only the first 3. One group of patients received the 3 drugs and bilateral pulmonary irradiation (approximately 1,500 rad in 2 wk). Preliminary analysis showed a local primary tumor control of approximately 90%. Patients with lesions in the pelvis and humerus had local failure rates of 13% (7 of 54) and 21.4% (6 of 28), respectively. The treatment groups differed significantly in the incidence of pulmonary metastasis. Patients treated with ...
An increased compendium of drugs useful in ocular motor system dysfunction has expanded our capacity to treat selected ocular motility disorders. Adjunctive therapeutic modes (e.g., Fresnel prisms and orthoptic exercises) can also be beneficial. PAN and see-saw nystagmus can be treated with baclofen. Downbeat nystagmus may respond to clonazepam therapy, and prisms may help if the nystagmus can be modified with convergence. Congenital nystagmus may respond minimally to drugs (e.g., baclofen), but prisms or surgical procedures, or both, are still the primary treatment modalities. Innovar may be helpful in patients with severe, incapacitating vestibular disorders, and scopolamine alone or in combination with promethazine may be beneficial in patients with milder ambulatory acute peripheral vestibular disorders. Benign positional vertigo is best treated initially with positional exercises before drug therapy is instituted. ...
Magnolia bark and ginger rhizome is a drug pair in many prescriptions for treatment of mental disorders in traditional Chinese medicine (TCM). However, compatibility and synergism mechanism of two herbs on antidepressant actions have not been reported. The aim of this study was to approach the rationale of the drug pair in TCM. We evaluated antidepressant-like effects of mixture of honokiol and magnolol (HMM), polysaccharides (PMB) from magnolia bark, essential oil (OGR) and polysaccharides (PGR) from ginger rhizome alone, and the possibility of synergistic interactions in their combinations in the mouse forced swimming test (FST) and tail suspension test (TST). Serotonin (5-HT) and noradrenaline (NE) levels in prefrontal cortex, hippocampus and striatum were also examined. 30 mg/kg HMM decreased immobility in the FST and TST in mice after one- and two-week treatment. OGR (19.5 or 39 mg/kg) alone was ineffective. The combination of an ...
We apply the framework developed in Target space duality I: general theory. We show that both nonabelian duality and Poisson-Lie duality are examples of the general theory. We propose how the formalism leads to a systematic study of duality by studying few scenarios that lead to open questions in the theory of Lie algebras. We present evidence that there are probably new examples of irreducible target space duality.
The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.
This paper illustrates how the techniques developed by the authors for capital cost targeting of mass exchange networks can be applied to determination of capital investment targets for reduction in effluent for existing systems involving mass exchange. The results is an impact diagram which shows the relationship between effluent reduction and capital investment, indicating a region of limiting return on investment as well as the maximum possible reduction in effluent. (au)
In order to facilitate observations of low energy nuclear reactions, a new type recoil mass-separator together with a new gas-jet target system is being developed at the tandem accelerator facility in Kyushu University. The expected mass-resolving power of the separator is 220 for a solid angle of 10 msr and the practical thickness of the gas-jet target will exceed 0.1 atm#centre dot#cm for the light elements of H and He. (author).
A portable fiber optic detector that senses the presence of specific target chemicals by electrostatically attracting the target chemical to an aromatic compound coating on an optical fiber. Attaching the target chemical to the coated fiber reduces the fluorescence so that a photon sensing detector records the reduced light level and activates an appropriate alarm or indicator.
A 16 l liquid parahydrogen target has been developed for a measurement of the parity-violating {gamma}-asymmetry in the capture of polarized cold neutrons on protons in the {rvec n} + p {yields} d + {gamma} reaction by the NPDGamma collaboration. The target system was carefully designed to meet the stringent requirements on systematic effects for the experiment and also to satisfy hydrogen safety requirements. The target was designed to preserve the neutron polarization during neutron scattering on liquid hydrogen (LH{sub 2}), optimize the statistical sensitivity to the {rvec n} + p {yields} d + {gamma} reaction, minimize backgrounds coming from neutron interaction with the beam windows of the target cryostat, minimize LH{sub 2} density fluctuations which can introduce extra noise in the gamma asymmetry signal, and control systematic effects. The target incorporates two mechanical ...
...2010-10-01 2010-10-01 false Energy Policy Act target group certification...Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION...Provisions and Clauses 952.226-73 Energy Policy Act target group...
DNA polymerase gamma from purified nuclei of EMT-6 cells (mice) seems to be identical to the mitochondrial DNA polymerase from the same source following several criteria. These two enzyme activities are strongly inhibited by ethidium bromide and acriflavin, while proflavin, acridine orange, daunomycin and chloroquine inhibition is less pronounced. In the case of DNA polymerases alpha and beta very little inhibition by ethidium bromide was observed. Intercalation of this dye in a poly dA-dT 12-18 template-primer was studied spectrophotometrically under conditions similar to those in the in vitro DNA polymerase assay. The polymerase assay. The inhibition by this drug of the mitochondrial DNA polymerase gamma activity was shown to be competitive at varying concentrations of TTP while the inhibition was of the non-competitive type at different concentrations of poly dA-dT 12-18. We conclude that the drug, most probably in the intercalated form, is ...
The atomic explosions in Hiroshima and Nagasaki made the name radiation itself become a nightmare. Notwithstanding this, radiation continued to serve the mankind specially in diagnosis of several human diseases and in the treatment of intractable malignancies. With their latest research tools biologists have now shown a significant shift in the earlier paradigm; even the concept that radiation initiates cancer appears to be no longer tenable. On the contrary, selective radiation doses inhibit growth of cancer cells and radiation in combination with many chemotherapeutic drugs, radiosensitizing chemicals and/or hyperthermia, is emerging as a new modality for cancer treatment which offers high therapeutic advantages. In addition, the deleterious effects of radiation can now be strategically counter poised by the use of many drugs and chemicals. This has been possible by the newer insights gained in the mechanism of biological effects of ...
Ex vivo (/sup 3/H)-8-hydroxy-2-(di-n-propylamino)-tetraline ((/sup 3/H)-DPAT) binding to the hippocampus has been utilized to determine the pharmacokinetic parameters of buspirone after i.v. and oral administration of this drug to rats. Intravenous buspirone rapidly penetrated the brain as demonstrated by a maximum inhibition of (/sup 3/H)-DPAT binding at 1 min. Elimination of drug from the brain was biphasic, with a first component half-life of 24.8 min and a second component half-life of 96 min. Oral buspirone at 3 times the i.v. dose produced less than one-third the maximum inhibition of (/sup 3/H)-DPAT binding compared to that observed with i.v. buspirone. The pharmacokinetic parameters of buspirone observed in the present study are in agreement with those reported previously. Thus, the ex vivo binding assay could be utilized to determine the bioavailability of the drug to the brain, and its duration of action. 20 ...
In drug development, Caco-2 cells are often employed to study the influence of membrane transporters on drug permeability. The aim of the current study was to characterize permeability and kinetic parameters of selected organic anionic compounds in Caco-2 cells, and to investigate whether the Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E(1) S) were used as model substrates. Possible inhibitors studied were TCA, E(1) S, taurolithocholic acid, fluvastatin, and glipizide. The effects of these compounds on initial uptake, apparent permeability, and intracellular end-point accumulations of the probe substrates were studied. Both interactions on apical and basolateral influx transporters were observed. These interactions were proposed to be mediated mainly by the apical sodium-dependent bile acid transporter and the organic ...
Binary mixtures of dipyrone and pitophenone hydrochloride are assayed by zero-crossing second- and third-derivative spectrophotometry and by ratio-spectra first- and second-derivative spectrophotometry. In the first method, calibration plots are linear at 266.5 and 302.5 nm (dipyrone, second derivative), and 257 and 286 nm (pitophenone second derivative) and 242 and 278.3 nm (dipyrone third derivative), and 228.5 and 300 nm (pitophenone, third-derivative). By the second method, lines of regression are linear at 235 and 262 nm (dipyrone, first derivative), and 229.5 and 288.5 nm (pitophenone, first-derivative), and 249.7 and 268 nm (dipyrone, second derivative), and 280.5 and 300 nm (pitophenone, second-derivative). In all methods calibration curves follow the Beer's law up to 40 microg/ml of each drug. LOD and LOQ values were calculated. The developed derivative spectrophotometric methods were applied to laboratory mixtures and to vials for these ...
To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 123}I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 123}I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis ...
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 terms of their S and E ...
Certain allelochemicals of the marine dinoflagellate Alexandrium tamarense cause lysis of a broad spectrum of target protist cells but the lytic mechanism is poorly defined. We first hypothesized that membrane sterols serve as molecular targets of these lytic compounds, and that differences in sterol composition among donor and target cells may cause insensitivity of Alexandrium and sensitivity of targets to lytic compounds. We investigated Ca^2^+ influx after application of lytic fractions to a model cell line PC12 derived from a pheochromocytoma of the rat adrenal medulla to establish how the lytic compounds affect ion flux associated with lysis of target membranes. The lytic compounds increased permeability of the cell membrane for Ca^2^+ ions even during blockade of Ca^2^+ channels wit...
A simple electromagnetic transport system was constructed to identify very rare positrons produced in a powerful laser beam interaction with a target. Testing experiments were carried out with CO[sub 2]-laser (10[sup 12] W/cm[sup 2]) beam pulses ([tau] = 50 ns, f = 0.01 Hz) focused on the copper target, as well as with a 96 MeV alpha-particle beam irradiated carbon target. The results showed that the developed system could be effectively used for positron identification and evaluation of their energy by means of a time-of-flight method. The computerized system to deal with this problem, together with others related to the power laser beam interaction with targets, has been constructed. (orig.).
The modeling methods used to compute the neutron-induced activation of target and near-target materials in the NIF facility are presented. A detailed space and energy description of the neutron environment in the different materials is provided. A new capability has been developed to treat in a general way the activation of debris produced in an operational regime of yield and no-yield experiments. First calculations are addressed to analyze the activity of the debris into the target chamber. The contribution of the different components to activity, interior dose rates, and waste disposal rating (WDR) is determined. The importance of the activation coming from primary irradiation in the target, and from secondary irradiation in debris deposited onto the first wall is assessed. Finally, waste hazards of the activated debris when removed out of the chamber and stored are analyzed. (authors)
Using static Michelson interferometer to get the spectrum information of measurement targets for spectrum identification, under the condition that the interference length is constant, the system can be optimized by BP neural network algorithm for the mixed spectral separation process. Thereby it can realize improving the recognition probability of camouflage target. Collecting the spectrum information in field of view (FOV) by the interferometer and linear array CCD detector, composing the set of mixed spectrum data, with known absorption spectrum of the material as a hidden layer of rules, it used BP neural network to separate the mixed spectrum data. Experiment with different distances, different combinations of mixed background spectrum as the initial data, using steel target (size: 1.5 m x 1.5 m) made of four kinds, the recognition probability of non-camouflage target is about 90% by BP neural ...
In the Fourth Dutch National Environmental Outlook (NMP, abbreviated in Dutch) of the National Institute of Public Health and the Environment (VROM), published in July 1997, possible future developments in the traffic and transport sector in the Netherlands are described for the period 1995-2020 and also evaluates present Dutch policies. NMP-4 also offers possible solutions for expected environmental problems. This report serves as a background document for the traffic and transport sector. With a view to present Dutch policies, the main conclusions drawn from the Outlook are that: (1) the policy targets for car and lorry use for 2010 will not be met, (2) the target for CO2 emissions from road transport for 2010 will not be met, (3) the NOx emission target for 2010 will be met for cars, but not for trucks, (4) the VOC emission target for 2010 will be met for cars, but not for trucks, and (5) the noise ...
This paper contributes to an understanding of pharmacogenomics-in-the-making by foregrounding a regulatory setting in which these technologies must be situated: decision-making about pharmaceutical reimbursement. Health care assessment organizations have been introduced in many countries to systematically address the issue of health care coverage. Using the example of Sweden, the process of deciding reimbursement status is shown to hinge on the creation of stable and clinically feasible categories of patients, diseases and drug responses. Through a series of analogous examples concerning conventional pharmaceuticals, it is argued that current mechanisms for categorizing reimbursable drugs could be upset when pharmacogenomic advances provide a means of making patients more specific objects ...
Ethnopharmacological relevance: Ethnobotanically driven drug-discovery programs include data related to many aspects of the preparation of botanical medicines, from initial plant collection to chemical extraction and fractionation. The Traditional Medicine Collection Tracking System (TM-CTS) was created to organize and store data of this type for an international collaborative project involving the systematic evaluation of commonly used Traditional Chinese Medicinal plants. Materials and methods: The system was developed using domain-driven design techniques, and is implemented using Java, Hibernate, PostgreSQL, Business Intelligence and Reporting Tools (BIRT), and Apache Tomcat. Results: The TM-CTS relational database schema contains over 70 data types, comprising over 500 data fields. Th...
Rationale Receptor occupancy study has been performed to evaluate pharmacokinetic profiles in new antipsychotic drug development. While these findings highlight the value of positron emission tomography (PET) for dose-finding study, what is unclear is if it is necessary to conduct these studies in patients with schizophrenia or whether studies in healthy volunteers are adequate. Objectives To determine if it is necessary to conduct dopamine receptor occupancy studies in patients with schizophrenia or whether studies in healthy volunteers are adequate for dose-finding study, we compared the concentration?occupancy relationship in terms of EC50 between patients and healthy volunteers. Methods Ten healthy volunteers and eight patients with schizophrenia participated in the study. We measured ...
In this work, the antibacterial effect of fluoroquinolones (FQs) upon Escherichia coli (E.coli) was measured with and without application of 40kHz ultrasound (US) stimulation. The research results demonstrated that simultaneous application of 40kHz US apparently enhanced the antibacterial effectiveness of FQs. That is, the synergistic effect was observed and the bacterial viability was reduced when FQs and US were combined. In addition, various influencing factors, such as FQs drug concentration, US irradiation time and solution temperature, on the inhibition of E.coli were also investigated. The antibacterial activity was enhanced apparently with increasing of FQs drug concentration, US irradiation time and solution temperature. Furthermore, we discussed preliminarily the mechanism of US ...
A hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1?mg/kg, prochlorperazine 1?mg/kg and caffeine 3?mg/kg, s.c.) and sumatriptan (20?mg/kg, s.c.) exert their central antinocicep...
An attempt is made to induce in mud crab (Scylla serrata) epileptiform activities that resemble the generalized epileptic seizures. Cerebral ganglion of crab was exposed in situ, to a convulsant drug pentylenetetrazole (PTZ) 100?mM, for induction of seizures. Also, crabs were pretreated with antiepileptic drug viz sodium valproate (120??mol/l) to inhibit epileptiform activities. The surface electrical discharges of cerebral ganglion were recorded using Unkelscope (MIT, USA) in control as well as experimental animals. The cerebral ganglion of crab showed a pattern of high cerebral electrical discharges after PTZ treatment compared to control. The sodium valproate promoted sedative action in control and prevented PTZ-mediated epileptiform discharges. Glutamate and GABA contents in cerebral g...
A widely used veterinary antibiotic, tetracycline (TC), has been incorporated in Langmuir-Blodgett (LB) films of dipalmitoylphosphatidic acid (DPPA) by means of two different procedures: co-transfer and incubation in solution. The resulting structures were characterized by means of contact angle and ellipsometric measurements. The presence of the antibiotic in the phospholipid film was evidenced by means of UV-Vis electronic absorption and infrared vibrational spectroscopy. The two sets of measurements unambiguously indicated the presence of the drug in the LB layer films obtained with both methods, although incubation led to a smaller content of immobilized tetracycline. In both cases, the drug was found to reside in the hydrophilic portion of the layers due to specific interactions of the dimethylamino group of the molecule with the polar head groups of the phospholipid.
Eight selected sulfonamide drugs were investigated as inhibitors of heat shock protein 90 (Hsp90). The investigation included simulated docking experiments to fit the selected compounds within the binding pocket of Hsp90. The selected molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low-energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were found to inhibit the ATPase activity of Hsp90 with IC50 values of 1.0, 2.6, and 1.5 mM, respectively. Our results suggest that these well-established sulfonamides can be good leads for subsequent optimization into potent Hsp90 inhibitors.
We have demonstrated that, with simple pH adjustment, volatile drugs such as methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and valproic acid could be analyzed rapidly from raw biofluid samples (e.g. urine and serum) without dilution, or extraction, using atmospheric pressure ionization. The ion source was a variant type of atmospheric pressure chemical ionization (APCI) that used a dielectric barrier discharge (DBD) to generate the metastable helium gas and reagent ions. The sample solution was loaded in a disposable glass pipette, and the volatile compounds were purged by nitrogen gas to be reacted with the metastable helium gas. The electrodes of the DBD were arranged in such a way that the generated glow discharge was confined within the discharge tub...
After irradiation at 254nm of aqueous solutions of the antipsychotic drug flupentixol, the structures of the photodegradation products were determined by ultra high performance liquid-chromatography linked to mass spectrometry. Fragmentation patterns of the parent ions were established on a hybrid linear ion trap-orbitrap mass spectrometer allowing accurate mass measurements of both parent and daughter ions. This allowed to propose plausible structures for the main photolysis products of flupentixol. A total of nine photoproducts were detected after irradiation of the drug. The main photoproduct is generated following the addition of a hydroxyl group on the double bond adjacent to the thioxanthene ring. Secondary photoproducts were also observed.
Abstract Objectives- Cyclodextrins are useful solubilizing excipients that have gained currency in the formulator's armamentarium based on their ability to temporarily camouflage undesirable physicochemical properties. In this context cyclodextrins can increase oral bioavailability, stabilize compounds to chemical and enzymatic degradation and can affect permeability through biological membranes under certain circumstances. This latter property is examined herein as a function of the published literature as well as work completed in our laboratories. Key findings- Cyclodextrins can increase the uptake of drugs through biological barriers if the limiting barrier component is the unstirred water layer (UWL) that exists between the membrane and bulk water. This means that cyclodextrins are mo...
The goal of this study is to determine whether physicists at the Russian Nuclear Weapons Institute can profitably service the need for computer aided drug design (CADD) programs. The Russian physicists` primary competitive advantage is their ability to write particularly efficient code able to work with limited computing power; a history of working with very large, complex modeling systems; an extensive knowledge of physics and mathematics, and price competitiveness. Their primary competitive disadvantage is their lack of biology, and cultural and geographic issues. The first phase of the study focused on defining the competitive landscape, primarily through interviews with and literature searches on the key providers of CADD software. The second phase focused on users of CADD technology to determine deficiencies in the current product offerings, to understand what product they most desired, and to define the potential demand for such a product.
One-electron oxidation of several derivatives of pyrazolin-5-one, including the drug antipyrine, were studied by pulse radiolysis of aqueous solutions. All the compounds were found to be oxidized by Br2 rapidly but considerably more slowly by weaker oxidants, such as peroxyl radicals. From redox equilibria using p-methoxyphenol and N,N,N',N'-tetramethyl-p-phenylenediamine as reference compounds, the one-electron oxidation potentials of the methyl-substituted 2-pyrazolin-5-ones were found to be in the range of 0.32-0.39 V versus normal hydrogen electrode. The relevance of these findings to the properties of the drug nafazatrom is discussed. Antipyrine was found to have a much higher oxidation potential, estimated as 1.2-1.5 V, which is rationalized on the basis of the phenyl substitution and lack of resonance stabilization of the radical cation.
This paper aims to provide a comprehensive review of the various models or simulations for predicting drug release from bulk-degrading systems. A brief description of bulk degradation processes and factors affecting the degradation rate, and consequently the release kinetics, is presented first. Next, several important classical models, often used as the basis for subsequent model development, are discussed. Both mathematical models and Monte-Carlo based simulations have been developed for controlled release from bulk-degrading systems. The mathematical models can be further subdivided into two categories. First, the diffusion-based models whose transport mechanism is mainly governed by diffusion, but with degradation-dependent diffusion coefficients. These are generally simpler and easier...
Abstract Introduction.- Cannabis (marijuana) is the most widely used illicit drug globally. Given the prevalence of nonprescription illicit drug abuse, there is a growing interest in the study of its potential effects on male sexual health. In this review, we discuss the effects of cannabis on male sexual health. Objective.- In this review, we discuss the effects of cannabis on male sexual health. Methods and Main Outcome Measure.- Critical review of scientific literature examining the impact of cannabis use on male sexual health. Results.- Studies examining the effects of cannabis use on male sexual function have been limited in both quality and quantity. Most results of these studies are conflicting and contradictory. While some did outline the beneficial effects of cannabis in enhancing...
PP2B is a Ca2+/calmodulin-dependent protein phosphatase that is ubiquitously expressed in mammals. Among other actions, it is an effector mechanism in NMDA-mediated glutamate neurotransmission as well as a regulator of GSK3? and MAPK signaling cascades. Because all of these mechanisms have demonstrable roles in the control of circadian rhythyms, we hypothesized that PP2B would be a key regulator of rhythm generation and entrainment, and that through inhibition of its phosphatase activity, the circadian system would be affected by immunosuppressant drug therapy. We report here that immunosuppressant drugs (cyclosporin A, FK506) (1) block the circadian responses to light that underlie photic entrainment; (2) produce circadian phase shifts with a characteristic nonphotic profile; and (3) disr...
The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.
Phenytoin (PHT), phenobarbital (PHB), lamotrigine (LTG), and topiramate (TPM) are some of the most widely used antiepileptic drugs (AEDs). Monitoring of their concentrations in serum is important for the treatment of epilepsy. A reference measurement procedure (RMP) for certification of PHT, PHB, LTG, and TPM in serum has been developed and critically evaluated. Isotopically labeled compounds of PHT, PHB, LTG, and TPM are used as internal standards for the four AEDs. The four drugs and their respective labeled internal standards are simultaneously extracted from serum using solid-phase extraction prior to reversed-phase liquid chromatography?tandem mass spectrometry (LC-MS/MS). Chromatographic separation was performed using a C18 column. Electrospray ionization (ESI) in the positive ion mo...
The presence of inefficient distribution networks and supply chains of medicines creates problems in that even if African countries can secure steep, sustainable cost-containing procurements, access to needed medicines may still be impaired. The expected health benefits from affordable pricing or subsidies on prices of medicines may not be realized. This article evaluates drug supply chains in African countries and advocates for consolidated private wholesale markets and multiplicity of retail pharmacies. Public supply chains should be shortened and supported by contracting out with private distributors, including wholesalers and retail pharmacies. Additionally, drug regulatory authorities should be allowed to charge registration fees that are proportionate to the costs of technical regula...
There is increasing evidence that adolescence, like early life, is a sensitive period in which ongoing brain development can be influenced by environmental factors. This review describes our use of social instability as a model of mild adolescent social stress, its effects on social interactions and on hypothalamic?pituitary?adrenal function over the course of the procedure and in response to new stressors. The effects of social instability are sex-specific, with qualitative differences between the sexes on HPA function over the course of the stressor procedure, and with greater effects in males on behaviour observed during the social instability and greater effects in females on behavioural responses to drugs of abuse into adulthood, long after the stress exposure. The results from invest...
Morphine sulfate (MS Contin), a proven analgesic in the treatment of cancer pain and chronic benign pain, seems to be a good analgesic for the treatment of burn pain. MS Contin is morphine sulfate incorporated in a wax cellulose matrix delivery system. This wax cellulose delivery system gives MS Contin its duration of action. Ten patients were enrolled in an open-labeled, nonrandomized study. The study was designed to examine the analgesic efficacy of MS Contin in the burn population. Each patient remained in the study for 6 days. The efficacy of the analgesic regimen was subjectively measured by the visual pain scale. The MS Contin group was retrospectively compared with a group of patients who were given continuous intravenous infusions of morphine. The two groups were matched according to age, burn size, surgical procedures, and hospital stay. The analgesic qualities of MS Contin were comparable to those of continuous intravenous morphine ...
In this work, a comprehensive model including heat transfer, fluid flow and solidification was used to evaluate the performance of a novel delivery system for a single-belt steel casting process. This near-net-shape casting, although still in development, is one of the most promising routes for casting of low-carbon steel in large scale. This paper focuses on the performance of a low-Re {kappa}-{epsilon} model that was employed to simulate the three-dimensional turbulent flows fully-coupled with heat transfer and macroscopic solidification. Simulations were run for the intended conditions of caster operation, and the results obtained with the {kappa}-{epsilon} were compared with the results obtained with an ad hoc viscosity model, where the molecular viscosity was boosted 100 times, uniformly throughout the computational domain. A semi-analytical solution was employed for validating the models and the results showed that the ad hoc viscosity model overestimated the ...
The use of the cervicograph with the incorporated action and alert lines in labour management in developing country obstetrics is now well established and patients in labour in Port Moresby have been thus managed since 1973. In this study the cerviograph was introduced in hospitals and health centres in Enga Province and the results analysed. Despite intensive tuition in its use, a large number of cervicographs were incorrectly constructed, especially in health centres, and its introduction made little difference to operative delivery or perinatal mortality rates. The proportion of patients crossing the action line was much higher than in Post Moresby but this difference was probably also largely due to the inaccuracy of many cervicographs. It is likely that these difficulties will not be overcome until many more nurses with intensive training in the use of the cervicograph are available and until more deliveries take place in health ...
The main objective of the present study is to investigate Turkey's natural gas (NG) demand and supplies by giving the structure of the Turkish gas industry, NG pricing policy, and NG agreements. Turkey began to import NG from Russia in 1987 under a contract that provided for the delivery of 6 billion cubic meters annually (Bcma) for 25 years. The first contract, signed in 1988, stipulates delivery of 2 Bcma over a 20-yr period. The build-up of the Turkish gas market started by introducing gas in power generation in 1987 and in fertilizer production in 1988. Later contracts provide for total imports of 4 Bcma from the late 1990s. NG sales started at 0.5 Bcm in 1987 and reached to around 16 Bcm in 2001. Turkish NG demand is projected to increase extremely rapidly in coming years, with the prime consumers expected to be NG-fired electric power plants and industrial users. (author)
Objective: Traditional nasolacrimal duct stenting possesses some shortcoming including difficulty of pulling ball head guide wire from the nasal cavity with turbinate hypertrophy and nasal septal deviation. The new method of nose-oral tube track establishment can overcome the forementioned and increase the successful rate. Methods: 5 F catheter and arterial sheath were modified to be nasolacrimal duct stent delivery device respectively. Antegrade dacryocystography was taken firstly to display the obstructed site and followed by the modified protocol of inserting the guide wire through nasolacrimal duct and nasal cavity, and establishing the stent delivery track for retrograde stent placement. Results: 5 epiphora patients with failure implantation by traditional method were all succeeded through the modified stenting (100%). During 6-mouth follow-up, no serious complications and reocclusion occurred. Conclusion: The establishment of ...
The effect of fetal distress on the neonatal brain was investigated by neonatal CT brain scan, FHR monitoring and mode of delivery. This study involved 11 cases of full term vertex delivery in which FHR was recorded by fetal direct ECG during the second stage labor. All infants weighed 2,500 g or more. FHR monitoring was evaluated by Hon's classification. Neonatal brain edema was evaluated by cranial CT histgraphic analysis (Nakada's method). 1) Subdural hemorrhage was noted in 6 of 7 infants delivered by vacuum extraction or fundal pressure (Kristeller's method). 2) Intracranial hemorrhage was demonstrated in all of 3 infants with 5-min. Apgar score 7 or less. 3) Two cases with prolonged bradycardia and no variability had intraventricular or intracerebral hemorrhage which resulted in severe central nervous system damage. 4) The degree of neonatal brain edema correlated with 5-min. Apgar score. 5) One case with ...
The effect of fetal distress on the neonatal brain was investigated by neonatal CT brain scan, FHR monitoring and mode of delivery. This study involved 11 cases of full term vertex delivery in which FHR was recorded by fetal direct ECG during the second stage labor. All infants weighed 2,500 g or more. FHR monitoring was evaluated by Hon's classification. Neonatal brain edema was evaluated by cranial CT histgraphic analysis (Nakada's method). 1) Subdural hemorrhage was noted in 6 of 7 infants delivered by vacuum extraction or fundal pressure (Kristeller's method). 2) Intracranial hemorrhage was demonstrated in all of 3 infants with 5-min. Apgar score 7 or less. 3) Two cases with prolonged bradycardia and no variability had intraventricular or intracerebral hemorrhage which resulted in severe central nervous system damage. 4) The degree of neonatal brain edema correlated with 5-min. Apgar score. 5) One case with prolonged bradycardia and no ...
RNA interference has become a powerful biological tool over the last decade. In this study, a tetracycline-inducible shRNA vector system was designed for silencing CFP expression and delivered alongside the yfp marker gene into Chinese hamster ovary cells using impalefection on spatially indexed vertically aligned carbon nanofiber arrays (VACNFs). The VACNF architecture provided simultaneous delivery of multiple genes, subsequent adherence and proliferation of interfaced cells, and repeated monitoring of single cells over time. Following impalefection and tetracycline induction, 53.1% 10.4% of impalefected cells were fully silenced by the inducible CFP-silencing shRNA vector. Additionally, efficient CFP-silencing was observed in single cells among a population of cells that remained CFP-expressing. This effective transient expression system enables rapid analysis of gene silencing effects using RNAi in single cells and cell populations.
Changes in contents of the two kinds of neuropeptides have been measured in the brains of postnatal G57BL/6J strain mice that received accumulative doses of 0, 0.05, 0.10 or 0.30 Gy respectively in utero from tritium #beta#-irradiation during the mother mice's pregnancy from the 12.5th day of gestation to the day of delivery. Dose response relationship for alteration in somatostatin content due to exposure to 0.10 Gy or above was observed, and it was also noted that 0.30 Gy could cause decrease in arginine vasopressin in hypothalamus. These results were consistent with findings in research on brain development and reflex behavior in the literature. 0.10 Gy exposure may represent a threshold for exposure to tritiated water within the range from day 12.5 of gestation to the day of delivery using change in content of somatostatin in hypophysis as a parameter.
We propose behavior-oriented services as a new paradigm of communication in mobile human networks. Our study is motivated by the tight user-network coupling in future mobile societies. In such a paradigm, messages are sent to inferred behavioral profiles, instead of explicit IDs. Our paper provides a systematic framework in providing such services. First, user behavioral profiles are constructed based on traces collected from two large wireless networks, and their spatio-temporal stability is analyzed. The implicit relationship discovered between mobile users could be utilized to provide a service for message delivery and discovery in various network environments. As an example application, we provide a detailed design of such a service in challenged opportunistic network architecture, named CSI. We provide a fully distributed solution using behavioral profile space gradients and small world structures. Our analysis shows that user behavioral profiles are ...
Sandia National Laboratories (SNL), acting for the US Department of Energy (DOE), contracts for and administers programs for the purpose of promoting the development and commercialization of large scale, transportable battery energy storage systems. Under DOE Co-Op Agreement No. DE-FC04-94AL99852, SNL has contracted for the development and delivery of an initial prototype 250 kW bridge that becomes an integral subsystem of a 2 MW/10 Second System that can be used by utility customers to protect power sensitive equipment from power disturbances. Development work includes field installation and testing of the prototype unit at a participating utility site for extended product testing with subsequent relocation to an industrial or commercial participating utility customer site for additional evaluation. The program described by the referenced document calls for cost sharing with the successful bidder and eventual title transfer to the participating utility. Prototype ...
Purpose: Various published reports involving intensity-modulated radiotherapy (IMRT) plans developed using automated optimization (inverse planning) have demonstrated highly conformal plans. These reported conformal IMRT plans involve significant target dose inhomogeneity, including both overdosage and underdosage within the target volume. In this study, we demonstrate the development of optimized beamlet IMRT plans that satisfy rigorous dose homogeneity requirements for all target volumes (e.g., #+-#5%), while also sparing the parotids and other normal structures. Methods and Materials: The treatment plans of 15 patients with oropharyngeal cancer who were previously treated with forward-planned multisegmental IMRT were planned again using an automated optimization system developed in-house. The optimization system allows for variable sized beamlets computed using a three-dimensional convolution/superposition dose ...
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This document outlines the major steps that must be taken by the Savannah River Site (SRS) to migrate the SRS information technology (IT) environment to the new architecture described in the Savannah River Site Computing Architecture. This document proposes an IT environment that is {open_quotes}...standards-based, data-driven, and workstation-oriented, with larger systems being utilized for the delivery of needed information to users in a client-server relationship.{close_quotes} Achieving this vision will require many substantial changes in the computing applications, systems, and supporting infrastructure at the site. This document consists of a set of roadmaps which provide explanations of the necessary changes for IT at the site and describes the milestones that must be completed to finish the migration.
Using the past diffusion trends of four renewable energy technologies for irrigation water pumping in India (SPV pumps, windmill pumps and biogas/producer gas driven dual fuel engine pumps), results of an attempt to project their future dissemination levels, have been presented in this study. The likely contribution of the renewable energy options considered in the study to the projected energy demand for irrigation water pumping in India has been estimated. Estimates of the associated investment requirements taking into account the learning effect have also been presented. (author)
The product of several advanced physical coal cleaning processes is a dry, ultrafine coal (DUC), in the order of 10 microns mean mass diameter. To utilize this fuel commercially, cost-effective, environmentally safe systems must be provided for the storage, transport, and handling of this finely divided form of fuel. The objective of the project described herein is the development of total logistics systems for DUC, including experimental verification of key features. The systems to be developed will provide for safe, economic, and environmentally protective storage and delivery of DUC for residential, commercial, and industrial uses. 20 figs.
The idle speed of an internal combustion engine is controlled in response to a variable ignition timing control signal from a microcomputer. The microcomputer derives this control signal as a function of the magnitude of engine speed variation which occurs during engine idle periods to cause the ignition timing to vary quickly in response to a transitory engine load variation. An auxiliary air delivery system may be advantageously incorporated in the idle speed control system to cooperate with the ignition timing control in response to the engine speed variation.
The goals of this paper are to describe the fabrication and complete evaluation of a dihydropyridine <- -> pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. Tissue distribution studies of "1"2"5I-labeled 4-iodoaniline and the redox agents were performed in rats. ["1"2"5I]Iodoaniline initially showed moderate brain uptake with subsequent release of the radioactivity from the brain. ["1"2"5I]Iodoaniline, however, when coupled to a dihydropyridine carrier showed significantly higher uptake and retention in the brain. (author).
The CyberKnife Robotic Radiosurgery System (Accuracy Incorporated, Sunnyvale, CA, USA) is used worldwide to treat tumors and neurological disorders anywhere in the body with sub-millimetre beam delivery accuracy. Accuracy has developed a number of new technologies in recent years to enhance the treatment of cancer patients. Such new technologies include a fast Monte Carlo Dose Calculation algorithm, Sequential Optimization dose planning, the IrisTM Variable Aperture Collimator, an 800 MU/min Linear Accelerator, and Optimized Path Traversal. These technologies enable physicists and physicians to plan treatments quickly and easily and deliver them with unrivalled accuracy and precision