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. Earlydrugdiscovery pipelines are poorly populated and the process of ...
The long and resource intensive process of drugdiscovery 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 drugdiscovery. 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)
Following a brief overview of the terrestrial distribution of boron in rocks, soil, and water, the history of the discovery, early utilization, and geologic origin of borate minerals is summarized....Full Text Available
Integration of solid-state biosensors and lipid bilayer membranes is important for membrane protein research and drugdiscovery. In these sensors, it is critical that the solid-state sensing...Full Text Available
The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with non-classical cellular targets. Unfortunately, target-based drugdiscovery against...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
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
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
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
Thiamin(e), also known as vitamin B1, is now known to play a fundamental role in energy metabolism. Its discovery followed from the original early research on the ‘anti-beriberi factor’...Full Text Available
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.
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...
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 ...
...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 ...
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
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
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...
The world of antibiotic drugdiscovery 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 drug targets 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...
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.
Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...
multi-parton interactions and underlying event structure, $\\gamma$-mediated processes and luminosity determination, Monte Carlo tuning and even MSSM Higgs discovery in central exclusive production. In this article, the forward detector instrumentation around the CMS interaction point is described and the prospects for diffractive and forward physics using the CMS forward detectors are summarized. In addition, first observation of forward jets as well as early measurements of the forward energy flow in the pseudorapidity range $3.15
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 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 drugdiscovery. 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...
Human pluripotent stem cells hold promising potential in many therapeutics applications including regenerative medicine and drugdiscovery. Over the past three decades, embryonic stem cell research has illustrated that embryonic stem cells possess two important and distinct properties: the ability to continuously self-renew and the ability to differentiate into all specialized cell types. In this article, we will discuss the continuing evolution of human pluripotent stem cell culture by examining requirements needed for the maintenance of self-renewal in vitro. We will also elaborate on the future direction of the field toward generating a robust and completely defined culture system, which has brought forth collaborations amongst biologists and engineers. As human pluripotent stem cell re...
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...
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We report the discovery of an active galactic nucleus (AGN) pair in the interacting galaxy system IRAS 20210+1121 at z = 0.056. An XMM-Newton observation reveals the presence of an obscured (N _H #approx# 5 x 10"2"3 cm"-"2), Seyfert-like (L _2_-_1_0_k_e_V = 4.7 x 10"4"2 erg s"-"1) nucleus in the northern galaxy, which lacks unambiguous optical AGN signatures. Our spectral analysis also provides strong evidence that the IR-luminous southern galaxy hosts a Type 2 quasar embedded in a bright starburst emission. In particular, the X-ray primary continuum from the nucleus appears totally depressed in the XMM-Newton band as expected in the case of a Compton-thick absorber, and only the emission produced by Compton scattering ('reflection') of the continuum from circumnuclear matter is seen. As such, IRAS 20210+1121 seems to provide an excellent opportunity to witness a key, early phase in the quasar evolution predicted by the theoretical models 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
funded these sensors as the first Discovery Mission of. Opportunity, part of the ... aboard a Russian Soyuz rocket. .... the Swedes on other projects, mainly sounding rocket projects. ..... incoming applications for the Fellowship Program, fielding ...
Background Fracture healing in osteoporosis is delayed. Quality and speed of fracture healing in osteoporotic fractures are crucial with regard to the outcome of patients. The question arises whether established antiosteoporotic drugs can further improve fracture healing. Materials and methods Osteoporosis manifests predominantly in the metaphyseal bone. Nevertheless, an established metaphyseal fracture model is lacking. A standardized metaphyseal fracture-healing model with stable plate fixation was developed for rat tibiae. The healing process was analyzed by biomechanical, gene expression, and histomorphometric methods in ovariectomized (OVX) and sham-operated rats (SHAM), compared to standardized estrogen (E)- and raloxifene (R)-supplemented diets. Results Estrogen and raloxifene impro...
Alcohol dependence (AD) is clinically and etiologically heterogeneous. The goal of this study was to explore AD subtypes among a sample of 1221 participants in the Irish Affected Sib Pair Study of Alcohol Dependence, all of whom met DSM-IV criteria for AD. Variables used to identify the subtypes included major depressive disorder, antisocial personality disorder, illicit drug dependence (cannabis, sedatives, stimulants, cocaine, opioids, and hallucinogens), nicotine dependence, the personality traits of neuroticism and novelty seeking, and early alcohol use. Using latent class analysis, a 3-class solution was identified as the most parsimonious description of the data. Individuals in a Mild class were least likely to have comorbid psychopathology, whereas a severe class had highest probabi...
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
Convection-enhanced drug delivery (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
Recent studies in elementary particle physics have made the need for an e{sup +}e{sup -} linear collider able to reach energies of 500 GeV and above with high luminosity more compelling than ever [1]. Observations and measurements completed in the last five years at the SLC (SLAC), LEP (CERN), and the Tevatron (FNAL) can be explained only by the existence of at least one particle or interaction that has not yet been directly observed in experiment. The Higgs boson of the Standard Model could be that particle. The data point strongly to a mass for the Higgs boson that is just beyond the reach of existing colliders. This brings great urgency and excitement to the potential for discovery at the upgraded Tevatron early in this decade, and almost assures that later experiments at the LHC will find new physics. But the next generation of experiments to be mounted by the world-wide particle physics community must not only find this new physics, they ...
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.).
A scientific breakthrough at Queen's University's Sudbury Neutrino Observatory has received major international recognition. The journal Science ranked the discovery that cracked the "neutrino problem" second, in the journal's top 10 scientific achievements of 2002 (1/2 page).
A previous report that 22 Vul is a zeta Aur--type eclipsing binary is supported by our discovery of evidence for an accretion shock cone in 22 Vul similar to those found in zeta Aurigae and 32 Cygni.
With the advent of powerful, widely-available mathematical software, combined with ever-faster computer hardware, we are approaching a day when both the discovery and proof of mathematical facts can be done in a computer-assisted manner. his article presents several specific examples of this new paradigm in action.
One of the central questions of molecular biology is the discovery of the semantics of DNA. This discovery relies in a critical way on a variety of expensive computations. In order to solve these computations, both parallel computers and special-purpose hardware play a major role.
... such as discovery, capabilities registration, lookup, and a ... Java- based toolkit for creating ... Multisensor, Multisource Information Fusion: Architectures ...
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
This paper surveys the growing number of industrial applications of data mining and knowledge discovery. We look at the existing tools, describe some representative applications, and discuss the major issues and problems for building and deploying successful applications and their adoption by business users. Finally, we examine how to assess the potential of a knowledge discovery application.
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
This paper describes the FACT system for knowledge discovery from text. It discovers associations - patterns of co-occurrence - amongst keywords labeling the items in a collection of textual documents. In addition, FACT is able to use background knowledge about the keywords labeling the documents in its discovery process. FACT takes a query-centered view of knowledge discovery, in which a discovery request is viewed as a query over the implicit set of possible results supported by a collection of documents, and where background knowledge is used to specify constraints on the desired results of this query process. Execution of a knowledge-discovery query is structured so that these back-ground-knowledge constraints can be exploited in the search for possible results. Finally, rather than requiring a user to specify an explicit query expression in the ...
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 ...
Success in improving treatment outcomes in childhood cancer has been achieved almost exclusively through multicenter and multidisciplinary clinical and applied research over several decades. While biologically rational as well as empirical approaches have led to combination chemotherapy and multimodality approaches to therapy, which have given rise to evidence-based practice standards, similar scientific rigor has not always been as evidently applied to modalities utilized to assess initial disease burden and, more important, response to investigational approaches to therapy. As the empirical approach to therapeutic advances has likely maximized its benefit, future progress will require translation of biologic discovery most notably from the areas of genomics and proteomics. Hence, attempts to improve efficacy of therapy will require a parallel effort to minimize collateral damage of future therapeutic approaches, and such a parallel approach will mandate the ...
Recent studies in elementary particle physics have made the need for an e{sup +}e{sup -} linear collider able to reach energies of 500 GeV and above with high luminosity more compelling than ever [1]. Observations and measurements completed in the last five years at the SLC (SLAC), LEP (CERN), and the Tevatron (FNAL) can be explained only by the existence of at least one particle or interaction that has not yet been directly observed in experiment. The Higgs boson of the Standard Model could be that particle. The data point strongly to a mass for the Higgs boson that is just beyond the reach of existing colliders. This brings great urgency and excitement to the potential for discovery at the upgraded Tevatron early in this decade, and almost assures that later experiments at the LHC will find new physics. But the next generation of experiments to be mounted by the world-wide particle physics community must not only find this new physics, they ...
Background. Through PSA screening the rate of prostate cancers detected at an early stage has increased significantly; thus a decrease in mortality can be expected in the near future. Despite all scientific efforts, however, the molecular mechanisms underlying the development and progression of prostate cancer remain poorly understood. Prostate cancer is a disease of aging men and epidemiological evidence supports a major contribution to its development through diet, lifestyle and environmental factors. Genetic instability is the basic phenomenon of tissue cell cancerisation. This instability can be hereditary or due to mutations and other chromosomal aberrations acquired during life. In recent years a large number of interesting data have been collected which show the relationships between focal atrophy and genetic instability of the prostate epithelia. Atrophy can be the result of prostatitis, ischemia as well as of oxidative stress (diet). Several chromosomal ...
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.
This paper studies neighbor discovery problem in wireless networks. A novel scheme, called compressed neighbor discovery is proposed, which assigns each node a unique signature and let nodes simultaneously transmit their signatures during the discovery period. The query node then determines, based on the superposition of the signatures, a small number of nodes as its neighbors, out of a large number of nodes in the network. This is fundamentally a sparse recovery problem. Using the proposed scheme, a single frame time suffices to achieve reliable discovery for large networks. This is in contrast to conventional schemes, where each node repeatedly transmits its identity with random delay, so that a receiver can identify each neighbor at least once without collision. Two practical, low-complexity discovery schemes are studied. The first scheme assigns sparse pseudo-random on-off ...
This certifies that the face of Flat Granny has flown in space aboard the Space Shuttle Discovery on mission STS-. 133 from February 24 - March 9, 2011. ...
Lead discovery in the pharmaceutical environment is largely an industrial-scale process in which it is typical to screen 1-5 million compounds in a matter of weeks using High Throughput Screening (HTS). This process is a very costly endeavor. Typically a HTS campaign of 1 million compounds will cost anywhere from $500000 to $1000000. There is consequently a great deal of pressure to maximize the return on investment by finding fast and more effective ways to screen. A panacea that has emerged over the past few years to help address this issue is in silico screening. In silico screening is now incorporated in all areas of lead discovery; from target identification and library design, to hit analysis and compound profiling. However, as lead discovery has evolved over the past few years, so h...
This paper proposes a new approach based on missing value pattern discovery for classifying incomplete data. This approach is particularly designed for classification of datasets with a small...Full Text Available
Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an...Full Text Available
"Physics in America is at a crossroads and in crisis, just as humanity stands on the verge of great discoveries about the nature of matter and the universe, a panel from the National Academy of sciences concludes in a new report."
Skip Over Navigation Links U.S. Department of Health & Human Services National Institutes of Health NIH...Turning Discovery into Health For Employees Staff Directory En Español...
evaluation, novelty detection, resource discovery, interfaces and visualization, digital libraries, computational social science, and cross-lingual information retrieval. The CIIR...
AbstractThe elucidation of the human and mouse genome sequence and developments in high-throughput genome analysis, and in computational tools, have made it possible to profile entire...Full Text Available
The Fermilab Steering Group has developed a plan to keep U.S. accelerator-based particle physics on the pathway to discovery, both at the Terascale with the LHC and the ILC and in the domain of neutrinos and precision physics with a high-intensity accelerator. The plan puts discovering Terascale physics with the LHC and the ILC as Fermilab's highest priority. While supporting ILC development, the plan creates opportunities for exciting science at the intensity frontier. If the ILC remains near the Global Design Effort's technically driven timeline, Fermilab would continue neutrino science with the NOVA experiment, using the NuMI (Neutrinos at the Main Injector) proton plan, scheduled to begin operating in 2011. If ILC construction must wait somewhat longer, Fermilab's plan proposes SNuMI, an upgrade of NuMI to create a more powerful neutrino beam. If the ILC start is postponed significantly, a central feature of the proposed Fermilab plan ...
Transcription for a hybrid SV40 promoter-beta globin coding sequence recombinant initiates from both early-early (EE) and late-early (LE) SV40 start sites (EES and LES) in the absence of DNA replication....Full Text Available
... Accession Number : ADB119274. Title : Transdermal Drug Delivery System. Stage 1. Volume 1. Descriptive Note : Final rept. 15 Aug 85-14 Oct 87,. ...
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
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
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
The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the...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
Magnetic drug targeting, using core-shell magnetic carrier particles loaded with anti-cancer drugs, is an emerging and significant method of cancer treatment. Gold shell-iron core nanoparticles (Fe@Au) were synthesized by the reverse micelle method with aqueous reactants, surfactant, co-surfactant and oil phase. XRD, XPS, TEM and magnetic property measurements were utilized to characterize these core-shell nanoparticles. Magnetic measurements showed that the particles were superparamagnetic at room temperature and that the saturation magnetization decreased with increasing gold concentration. The anti-cancer drug doxorubicin (DOX) was loaded onto these Fe@Au nanoparticle carriers and the drug release profiles showed that upto 25% of adsorbed drug was released in 80 h. It was found that the amine (-NH2) group of DOX binds to the gold shell. An in vitro apparatus simulating the human ...
...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...
Short review of works on astatine chemistry carried out by authors for the last thirty years are done. Discovery of single-charged cation stable in aqueous solutions is predominant attainment of authors in the branch of inorganic chemistry. The first successful synthesis of heptavalent astatine compounds is a new and significant result of the last years. New direction in the chemistry of the fifth halogen is organic chemistry of astatine
... The pharmacologist/toxicologist and the statistician will jointly determine if a statistical review is needed and when the review should be done. ...
The main goal of local drug delivery is to increase the concentration of a specific therapeutic agent in a target tissue with minimal nontarget distribution. Compared to systemic therapy, local drug delivery provides a high level of therapeutic efficacy with minimal systemic effects. The current primary imaging modality for drug delivery 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 ...
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...
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 drug delivery compared ...
Magnetic particles have become very promising materials for drug delivery. However, preparation of magnetite particles with high surface area, biocompatibility, strong magnetic response, and suitable particle size still remains a major challenge. In this report, magnetite nanocrystal clusters with high surface areas were fabricated through a solvothermal process by introducing ammonium acetate as a porogen and trisodium citrate as a surface modification agent. The porosity, which was controlled by the reactant concentration, has been investigated in detail. The surface area of the nanocrystal clusters was as high as 141?m(2) g(-1) . Ibuprofen, as a model drug, was entrapped into the magnetite carriers. The interfacial interaction between the carboxylic groups on the drug molecules and the carboxylate groups on the carriers enhanced the loading efficiency. Low cytotoxicity in MCF-7 cell and in vitro constant ...
BackgroundDue to the high morbidity and mortality of fulminant hepatitis, early diagnosis followed by early effective treatment is the key for prognosis improvement. So far, little...Full Text Available
In the decade before the discovery of insulin, the prominent American physicians Frederick Allen and Elliott Joslin advocated severe fasting and undernutrition to prolong the lives of diabetic patients....Full Text Available
The use of Sleeping Beauty transposons as somatic mutagens to discover cancer genes in hematopoietic tumors and sarcomas has been documented. Here, we discuss the future of Sleeping...Full Text Available
Significant emphasis has recently been placed on the characterization of the human cancer genome. This effort has been assisted by the development of new DNA sequencing technologies that allow...Full Text Available
When faced with a harsh climate or inadequate food, some mammals enter a state of suspended animation known as torpor. A major goal of torpor research is to determine mechanisms that integrate...Full Text Available
Mouse genetic resources include inbred strains, recombinant inbred lines, chromosome substitution strains, heterogeneous stocks, and the Collaborative Cross (CC). These resources were generated through...Full Text Available
Inhibiting insulin/IGF-1 signalling extends lifespan and delays age-related disease in species throughout the animal kingdom. This life-extension pathway, the first to be defined, was discovered through...Full Text Available
The realization that there existed a G-protein coupled signal transduction mechanism developed gradually and was initially the result of an ill fated quest for uncovering the mechanism of action...Full Text Available
BackgroundDiscovery of biomarkers that are correlated with therapy response and thus with survival is an important goal of medical research on severe diseases, e.g. cancer. Frequently,...Full Text Available
Protein post-translational modifications are an important biological regulatory mechanism, and the rate of their discovery using high throughput techniques is rapidly increasingly. To make use of this...Full Text Available
The sensitivity of different renal regions to xenobiotics requires the development of a multiplex immunoassay for the simultaneous analysis of kidney biomarkers. Calbindin D28K is a distal tubule-specific...Full Text Available
In 18 months the Canadian Medical Discoveries Fund (CMDF) has attracted investments worth $180 million to spend on biotechnology and medical research. Although eight initial investments totalled only...Full Text Available
The NS together with a gamma ray sensor make up the Gamma- Ray and ... A simplified view of the interactions between incoming cosmic rays and the .... held in Huntsville, Alabama, at the U.S. Space and Rocket Center on January 2830. ...
BackgroundRecently, the discovery of copy number variation (CNV) led researchers to think that there are more variations of genomic DNA than initially believed. Moreover, a certain...Full Text Available
The discovery that aerobic exercise increases adult hippocampal neurogenesis and can enhance cognitive performance holds promise as a model for regenerative medicine. This study adds two new...Full Text Available
Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential...Full Text Available
Healthcare-associated infections (HAIs) take a major human toll on society and reduce public confidence in the healthcare system. The current convergence of scientific, public, and legislative...Full Text Available
Zebrafish transgenesis is a powerful and increasingly common strategy to assay vertebrate transcriptional regulatory control. Several challenges remain, however, to the broader application of...Full Text Available
We have discovered interstellar rubidium by observing the resonance line of Rb I at 7800 A toward zeta Oph. This is the heaviest element yet detected within the interstellar medium, and our detection of this element is important for understanding the history of nucleosynthesis in the solar neighborhood.
Details of ion transporting abnormalities in cystic fibrosis airway epithelium are now known. The central hypothesis, that excessive drying of the airway surfaces is a primary event that leads to all...Full Text Available
The discovery that hepatitis B virus (HBV) integrates into host chromosomes raises the question of whether such viral DNA integration correlates directly with the activation of specific oncogenes or...Full Text Available
Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable...Full Text Available
A remarkable discovery of recent years is that, despite the complexity of ageing, simple genetic interventions can increase lifespan and improve health during ageing in laboratory animals. The pathways...Full Text Available
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
The relationship between short term relative sea-level oscillations and the reef, off-reef deposits geometry of an Upper Devonian third order sequence highstand of the Nisku Formation in west central Alberta was studied through the analysis of high resolution sequence stratigraphy. Hydrocarbon generation was reconstructed by total organic carbon values and migration patterns that were dependent on the geometry of three fourth order sequences. This stratigraphic reconstruction provided the key to recent hydrocarbon discoveries such as in the Brazeau southern reef margin.
Recessive mutations of the early phase change (epc) gene in maize affect several aspects of plant development. These mutations were identified initially because of...Full Text Available
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.
The aim of the paper is to review the role of interventional radiology in the management of hemodialysis vascular access and complications in renal transplantation. The evaluation of patients with hemodialysis vascular access is complex. It includes the radiology/ultrasound (US) evaluation of the peripheral veins of the upper extremities with venous mapping and the evaluation of the central vein prior to the access placement and radiological detection and treatment of the stenosis and thrombosis in misfunctional dialysis fistulas. Preoperative screening enables the identification of a suitable vessel to create a hemodynamically-sound dialysis fistula. Clinical and radiological detection of the hemodynamically significant stenosis or occlusion demands fistulography and endovascular treatment. Endovascular prophylactic dilatation of stenosis greater than 50% with associated clinical abnormalities such as flow-rate reduction is warranted to prolong access patency. The technical success ...
The evaluate the signs of aortic intramural hematoma with helical CT and the diagnostic role of this technique in patients with this condition. It was reviewed the CT findings of 396 patients submitted to emergency examinations for suspected aortic dissection from 1995 to 1999. Only 18 patients (6 women and 12 men) had CT signs of aortic intramural hematoma. Helical CT studies were carried out with the following parameters: slice thickness 10 mm, reconstruction index 10, feed 1.5 mm, conventional algorithm with minimum values of 130 kV and 125mA. All patients were examined with dynamic contrast-enhanced CT, before and after a power injection of 130 mL ionic contrast material. It was studied: hematoma localization and longitudinal extension; thickness and density of aortic wall; presence and location of intimal calcifications; integrity of intimal wall; hemo mediastinum and/or hemo thorax. Aortic wall thickening appeared as a high density crescent-shaped area at baseline CT and had low ...
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
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
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
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
Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracel...
ObjectiveEpidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and...Full Text Available
Gastrointestinal patches represent a novel multiparticulate drug delivery system able to increase the intestinal absorption of drugs with poor bioavailability. The number of patches to administer is a critical issue since it is related to the surface and drug concentration at the absorption site. The objective of this article is to evaluate the effect of the number of administered patches on the final absorption of leuprolide, a peptide chosen as model drug, assuming complete adhesion of all the devices to the intestinal membrane. The same dose of leuprolide was encapsulated into 2, 4 and 6 patches; the resulting intestinal absorption profiles were measured with the Ussing chamber ex vivo experimental setup and compared between them. The results showed that varying the number of patches, t...
... 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
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 ...
When the history of neutrons is considered, three large discoveries are recalled, that is, the discovery of neutrons by Chadwick in 1932, the discovery of the nuclear fission of uranium by Hahn and Strassmann in 1938, and the continuation of chain reaction in nuclear fission by Fermi and others in 1942. In neutron capture reaction, the reaction cross section can become very large. The fields of research, to which neutrons have contributed most as the experimental probe, are neutron activation analysis and neutron diffraction. The development of the prompt gamma ray analyzer at the JRR-3M in Japan Atomic Energy Research Institute is reported. This method eliminates the various defects in ordinary neutron activation analysis. By installing the cold neutron source with hydrogen cooling in the JRR-3M, the new field of research was opened. As the combination of a lead-moderated spectrometer and an electron beam type accelerator, ...
High-throughput synthesis and screening methods have been developed for the discovery of highly active catalysts for the control of emissions from stationary and mobile sources. Low temperature CO oxidation, CO methanation, NOx abatement and the destruction of Volatile Organic Compounds (VOCs) will be discussed. The discovery libraries for primary screening consisted of both 11x11 and 16x16 catalyst arrays on 3 inch and 4 inch quartz wafers, respectively. Catalysts were prepared by robotic liquid dispensing techniques and screened for catalytic activity in Symyx's Scanning Mass Spectrometer. The screening protocols encompassed mixed metal oxides, perovskites and supported base and noble metals. Active hits were further optimized in focus libraries using shallower compositional gradients. The ScanMS is a fast serial screening tool that uses flat wafer catalyst surfaces, local laser heating, a scanning/sniffing nozzle and a quadrupolar ...
In recent years, discovery of association rules among itemsets in a large database has been described as an important database-mining problem. The problem of discovering association rules has received considerable research attention and several algorithms for mining frequent itemsets have been developed. Many algorithms have been proposed to discover rules at single concept level. However, mining association rules at multiple concept levels may lead to the discovery of more specific and concrete knowledge from data. The discovery of multiple level association rules is very much useful in many applications. In most of the studies for multiple level association rule mining, the database is scanned repeatedly which affects the efficiency of mining process. In this research paper, a new method for discovering multilevel association rules is proposed. It is based on FP-tree structure and uses cooccurrence frequent item tree to ...
The discovery that the cosmic expansion is accelerating has been followed by an intense theoretical and experimental response in physics and astronomy. The discovery implies that our most basic notions about how gravity work are violated on cosmological distance scales. One simple fix is the introduction of a cosmological constant into the field equations for general relativity. However, the extremely small value of the cosmological constant, relative to theoretical expectations, has led theorists to explore a wide variety of alternative explanations that involve the introduction of an exotic negative-pressure fluid or a modification of general relativity. Here we briefly review the evidence for cosmic acceleration. We then survey some of the theoretical attempts to account for it, including the cosmological constant, quintessence and its variants, mass-varying neutrinos, and modifications of general relativity, such as scalar-tensor and $f(R)$ ...
Thailand's demand for gas will outstrip supplies in the late 1990s as rapid economic growth continues. Gas will be a cornerstone for Thai energy policy throughout the growth, although sources in neighboring countries need development. Thai gas production will rise 25% from 1992 to average 1 bcfd by 1995. Including production from new discoveries, production could rise to 1.5 bcfd by 2000, up almost 90% from the 1992 level. Increased gas flow output in the mid-1990s will be due largely to development of Gulf of Thailand fields. By 1998, production from Gulf of Thailand fields will not be enough to offset the decline in today's fields. Thailand will need to import more than 1 bcfd by 2005 in the absence of future discoveries in the country. The paper discusses new pipelines and imports.
Discovery of better biomarkers for diagnosis, prognosis, and therapy-response prediction is the most critical task of a scientific quest aimed at developing newly designed, tailor-made therapies for patients with cancer. Consequently, a proteome wide analysis, in addition to genomic studies, is an absolute requirement for a complete functional understanding of tumor biology. Ultra-sensitive, high-performance Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) currently holds an important role in fulfilling the demands of biomarker discovery. In this review, we describe the applicability of FTICR MS for breast cancer proteomics, particularly for the analysis of complex protein mixtures obtained from a limited number of cells typically available from clinical specimens.
Glial fibrillary acidic protein (GFAP) is the main intermediate filament protein in mature astrocytes, but also an important component of the cytoskeleton in astrocytes during development. Major recent developments in astrocyte biology and the discovery of novel intermediate filament functions enticed the interest in the function of GFAP. The discovery of various GFAP splice variants gave an additional boost to explore this protein in more detail.The structural role of GFAP in astrocytes has been widely accepted for a long time, but over the years, GFAP has been shown to be involved in astrocyte functions, which are important during regeneration, synaptic plasticity and reactive gliosis. Moreover, different subpopulations of astrocytes have been identified, which are likely to have distinc...
When testing multiple hypothesis in a survey --e.g. many different source locations, template waveforms, and so on-- the final result consists in a set of confidence intervals, each one at a desired confidence level. But the probability that at least one of these intervals does not cover the true value increases with the number of trials. With a sufficiently large array of confidence intervals, one can be sure that at least one is missing the true value. In particular, the probability of false claim of detection becomes not negligible. In order to compensate for this, one should increase the confidence level, at the price of a reduced detection power. False discovery rate control is a relatively new statistical procedure that bounds the number of mistakes made when performing multiple hypothesis tests. We shall review this method, discussing exercise applications to the field of gravitational wave surveys.
The study of extragalactic planetary nebulae (EPN) is a rapidly expanding field. The advent of powerful new instrumentation such as the PN spectrograph has led to an avalanche of new EPN discoveries both within and between galaxies. We now have thousands of EPN detections in a heterogeneous selection of nearby galaxies and their local environments, dwarfing the combined galactic detection efforts of the last century. Key scientific motivations driving this rapid growth in EPN research and discovery have been the use of the PNLF as a standard candle, as dynamical tracers of their host galaxies and dark matter and as probes of Galactic evolution. This is coupled with the basic utility of PN as laboratories of nebula physics and the consequent comparison with theory where population differences, abundance variations and star formation history within and between stellar systems informs both stellar and galactic evolution. Here we pose some of the ...
The discovery of extra-solar planets is one of the greatest achievements of modern astronomy. There are now more than 200 such objects known, and the recent detection of planets with masses approximately 5 times that of Earth demonstrates that extra-solar planets of low mass exist. In addition to providing a wealth of scientific information on the formation and structure of planetary systems, these discoveries capture the interest of both scientists and the wider public with the profound prospect of the search for life in the Universe. We propose an L-type mission, called Darwin, whose primary goal is the study of terrestrial extrasolar planets and the search for life on them. By its very nature, Darwin advances the first Grand Theme of ESA Cosmic Vision. Accomplishing the mission objectives will require collaborative science across disciplines ranging from planet formation and atmospheres to chemistry and biology, and these disciplines will ...
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...
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...
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...
A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.
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...
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...
A series of deletion mutants extending from -250 toward the capsite has been constructed in the early promoter region of the adenovirus 2 EIIa gene and tested both in vitro, and in vivo after transfection...Full Text Available
Sunbed use is associated with increased risk of melanoma. Younger people might be more susceptible to the carcinogenic effects of ultraviolet radiation. We investigated the association between...Full Text Available
The changes in protein species synthesized during early Drosophila embryogenesis were characterized by two-dimensional electrophoresis. Of the 261 proteins scored, 68 (26%) show dramatic changes in...Full Text Available
AbstractStudies performed to identify early events of ovarian cancer and to establish molecular markers to support early detection and development of chemopreventive regimens have been...Full Text Available
Purpose.To estimate the prevalence of early and late age-related macular degeneration (AMD) in India.Methods.Of 7518 people aged 60 years and older...Full Text Available
Cognitive rehabilitation is an effective intervention for addressing cognitive impairments in patients with schizophrenia. Previous research has shown that the early application of Cognitive...Full Text Available
The origin of myofibroblasts or myofibroblastic cells in the desmoplastic stroma associated with carcinoma invasion has been controversial. In the early invasive area of a rectal adenocarcinoma reported...Full Text Available
Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable...Full Text Available
Photodynamic therapy (PDT) is an established endoscopic technique for ablating Barrett’s esophagus with high-grade dysplasia or early-stage intraepithelial neoplasia. The most common clinically...Full Text Available
The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development...Full Text Available
BackgroundPeak bone mass, attained by early adulthood, is influenced by genetic and life-style factors. Early infant feeding and duration of breastfeeding in particular, associate...Full Text Available
SUMMARYDendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter....Full Text Available
In both humans and songbirds, infants learn vocalizations by imitating the sounds of adult tutors with whom they interact during an early sensitive period. Vocal learning occurs in few animal taxa;...Full Text Available
BackgroundOne-stage implant placement has clinically acceptable treatment outcomes. Among other advantages, it may allow investigation of early wound healing. The...Full Text Available
Higher plants use photoperiodic cues to regulate many aspects of development, including the transition from vegetative to floral development. The EARLY FLOWERING3 (ELF3)...Full Text Available
Instantaneous cross sectional flow velocity profiles from early mitral flow in 10 healthy men were constructed by time interpolation of the velocity data from each point in sequentially delayed two...Full Text Available
Early simian virus 40-specific mRNA was isolated from lytically infected and stably transformed cells and analyzed with respect to the 5'-terminal cap content. An analogous diversity of capped structures...Full Text Available
Mission losses were incurred by an early warning satellite and a Milstar-2 communications satellite when their launch vehicles malfunctioned, the first, ...
Purpose of reviewTo summarize recent advances in the classification of preradiographic axial spondyloarthritis (SpA).Recent findingsFull Text Available
... 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
To capitalize on the response of tumor cells to ionizing radiation, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced...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
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
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
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
Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug-delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate...Full Text Available
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 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 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
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
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 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
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
BackgroundGene expression profiling and the analysis of protein-protein interaction (PPI) networks may support the identification of disease bio-markers and potential drug targets....Full Text Available
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
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
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
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
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
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...
Bridged monobactam {beta}-lactamase inhibitors were prepared and evaluated as potential partners for combination with imipenem to overcome class C {beta}-lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective in both in vitro and in vivo assays and was selected for preclinical development.
The second in a series of flights to assemble the Japanese segment of the International Space Station saw the mammoth Kibo module delivered to the complex complements of Discovery and its crew on the STS-124 mission. Kibo, the Japanese word for u201chopeu201d would house dozens of experiments and serve as a platform for external payloads brought to the complex on subsequent Shuttle flights and the Japanese u201cKounotoriu201d H-2 Transfer Vehicle cargo ship.
The discovery of a new particle in the Higgs searches being prepared for LHC will not guarantee that the Standard Model Higgs boson has been seen. This paper discusses the possibilities for measuring the spin, parity and couplings of the particle, under the assumption that it does in fact behave like the Standard Model Higgs. The key question, which cannot alas be answered, is: if it looks like a dog, and barks like a dog, how much of the DNA must we analyse to be sure that it is a dog?
... Quenching is one of the most fundamentally complex processes in the heat treatment of metals, and it is something on which mechanical properties and distortion of engineering components depend. AU$236.36 ex-GST Terms and Conditions Eyes on the Skies: 400... Adopted as the official book of the International Year of Astronomy (IYA) 2009, this stunningly illustrated history of telescopic discovery spans the range ...
The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein...Full Text Available
Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic viruses group (PTLV). The high percentage...Full Text Available
The polymer industry is a young industry that has undergone tremendous growth and change over the last sixty years. Many important discoveries in polymer science have been accidental. Most of the learning has been by trial and error and most of the understanding is still basically empirical--make a polymer material or compound and then put it to the test to study what it is and how it performs. This article provides an overview of what polymers and polymer compounds are, why they behave as they do, and it discusses several examples of failures of rubber and plastic components.
...Explore - The Lab - Australian Broadcasting Corporation's Gateway to Science Radio TV Shop News Sport Local Children Science Environment more Topics help Science Home News in Science Features Explore TV & Radio Dr Karl Play Podcasts DNA - The discovery of the double helix structure of DNA completely changed biology and opened up the new field of genetics. The 'backbone of life' has given us the human genome, stem cell research, ...
DescriptionEnzymes are natural catalysts that are used increasingly to replace environmentally harmful chemicals and to achieve better catalytic selectivity during pulp and paper processing. The main objective of this project is to identify novel plant enzymes for deeper understanding of the process of fibre formation and for future improvement of the quality parameters of wood fibres. Specific modification of the fibre characteristics will facilitate their use as raw materials for the current pulp and pap [continued...
The Baldwin Effect, a negative correlation between emission-line equivalent width and luminosity in active galactic nuclei, is still of interest as a diagnostic of accretion physics nearly thirty years after its discovery. This review examines recent developments in the study of correlations between line and continuum emission in AGNs, as measured both in ensembles and in individual sources.
Metadata can be used to support accessibility in connection with improved discovery. ...certain metadata elements provide information about what capabilities are needed--either perceptual-motor, cognitive, socio-economic or geographic--to make use of a resource. This cam improve the ability of users who are disadvantaged in these ways to find resources that meet their needs--and avoid ones [resources] that do not.
A work on the world of astrophysics primarily for lay readers. The author writes only about the discoveries he ''experienced'' during the past 25 years (before 1979). Illustrated somewhat in color plus a set of superb colar plates. Contents, abridged: The long life of stars. The life story of the sun. The life story of massive stars. The end of stars. How stars are born. Planets and their inhabitants.
A novel drug delivery system for the treatment of brain tumors was formulated by methotrexate (MTX)-loaded polymeric nanoparticles (NPs) based on Glycol chitosan (GCS) and Dextran sulfate (DS). The physicochemical properties of resulting particles were investigated, evidencing the contribution of these nanoparticles for brain targeting. In vitro release of MTX was also evaluated. The GCS-DS nanoparticles have been developed based on the modulation of ratio show promise as a system for controlled delivery of the drug to the brain. PMID:21782844
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 drug delivery 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.
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.
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 ...
The last decade has produced an explosion in neuroscience research examining young children's early processing of language that has implications for education. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. In the arena of language, the neural signatures of learning can be documented at a remarkably early point in development, and these early measures predict performance in children's language and pre-reading abilities in the second, third, and fifth year of life, a finding with theoretical and educational import. There is evidence that children's early mastery of language requires learning in a social context, and this finding also has important implications for education. Evidence relating socioeconomic status (SES) ...
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 introduce a novel search technique that can identify trans-Neptunian objects in three to five exposures of a pointing within a single Hubble Space Telescope (HST) orbit. The process is fast enough to allow the discovery of candidates soon after the data are available. This allows sufficient time to schedule follow-up observations with HST within a month. We report the discovery of 14 slow-moving objects found within 50 of the ecliptic in archival data taken with the Wide Field Channel of the Advanced Camera for Surveys. The luminosity function of these objects is consistent with previous ground-based and space-based results. We show evidence that the size distribution of both high and low inclination populations is similar for objects smaller than 100 km, as expected from collisional evolution models, while their size distribution differs for brighter objects. We suggest that the two populations formed in different parts of the ...
In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane ...
Many data mining tools cannot be used directly to analyze the complex sets of relations which are found in large database systems. In our experience, data miners rely on a well-defined data model, or the knowledge of a data expert, to isolate and extract candidate data sets prior to mining the data. For many databases, typically large legacy systems, a reliable data model is often unavailable and access to the data expert can be limited. In this paper we use reverse engineering techniques to infer a model of the database. Reverse engineering a database can be seen as knowledge discovery in its own right and the resulting data model may be made available to data mining tools as background knowledge. In addition, minable data sets can be produced from the inferred data model and analyzed using conventional data mining tools. Our approach reduces the data miner`s reliance on a well-defined data model and the data expert.
We present the discovery of a Baldwin effect in 8 nearby Seyfert galaxies for the three most prominent mid-infrared forbidden emission lines observable from the ground that are commonly found in AGN, [ArIII](8.99 micron), [SIV](10.51 micron), and [NeII](12.81 micron). The observations were carried out using the VLT/VISIR imager and spectroraph at the ESO/Paranal observatory. The bulk of the observed line emission comes from the inner <0.4 arcsec which corresponds to spatial scales <100 pc in our object sample. The correlation index is approximately -0.6 without significant difference among the lines. This is the strongest anti-correlation between line equivalent width and continuum luminosity found so far. In the case of Circinus, we show that despite the use of mid-infrared lines, obscuration by either the host galaxy or the circumnuclear dust torus might affect the equivalent widths. Given the small observed spatial scales from which most of the line ...
Yet designed to measure charged component of the cosmic rays, the foreseen Alpha Magnetic Spectrometer (AMS-02) could also release {gamma}-ray studies, in the energy range from GeV to TeV, using the tracker system, for {gamma}-rays converted in e{sup +}e{sup -} pair, and the electromagnetic calorimeter. In the first part of the thesis are described the calibrations and the performances of the engineering model of the calorimeter, obtained from the analysis of data taken during a test-beam performed at CERN in July 2002. In the second part of the thesis, the AMS-02 discovery potential for {gamma}-astrophysics is presented. While exposure maps of the {gamma}--sky are computed for one year of data taking with the {gamma}--detectors, the acceptance of the calorimeter is obtained from Monte-Carlo simulations. The AMS-02 potential is then estimated for signals from the Vela pulsar and for some supersymmetric signals from the Galactic Center. (author)
Most of the presently identified exoplanets have masses similar to that of Jupiter and therefore are assumed to be gaseous objects. With the ever-increasing interest in discovering lower-mass planets, several of the so-called super-Earths (i.e., with masses in the interval 1 M_earth < M < 10 M_earth), which are predicted to be rocky, have already been found. Here we report the possible discovery of a planet around the M-type star GJ 436 with a minimum mass of 4.8+/-0.6 M_earth and a true mass of ~5 M_earth, which makes it the least massive planet around a main-sequence star found to date. In contrast with other discoveries, the planet is identified from its perturbations on an inner Neptune-mass transiting planet (GJ 436b), by pumping eccentricity and producing secular variations in the orbital inclination. Analysis of published radial velocity measurements indeed reveals a significant signal corresponding to an orbital period that is ...
Two researchers, Tom Goreau of the Discovery Laboratory in Jamaica and Raymond Hayes of Howard University, claim that they have evidence that nearly clinches the temperature connection to the bleached corals in the Caribbean and that the coral bleaching is an indication of Greenhouse warming. The incidents of scattered bleaching of corals, which have been reported for decades, are increasing in both intensity and frequency. The researchers based their theory on increased temperature of the seas measured by satellites. However, some other scientists feel that the satellites measure the temperature of only the top few millimeters of the water and that since corals lie on reefs perhaps 60 to 100 feet below the ocean surface, the elevated temperatures are not significant.
Approximately 1.2 million kg of uranium oxide (yellow cake) has been produced from the area surrounding Gunnison, Colorado. Over 99 percent of this has come form the Cochetopa and Marshall Pass districts. Uranium in both districts and many of the other occurrences is associated closely with fault and shear zones which cut brittle host formations (sandstones and dolomites) of Paleozonic and Mesozoic age. Minor uranium occurrences are in pegmatites and shear zones in Precambrian rocks, Cambrian vein material, and sandstones of Tertiary age. In the paper presented, the uranium occurences are described by districts. In addition, possibilities for additional discoveries are discussed. (JMT)
The mammalian circadian timing system is organized into hierarchical structures with a central clock in the suprachiasmatic nucleus (SCN) and subsidiary peripheral oscillators. After the discovery of the local clockwork in peripheral organs and tissues, which have a molecular makeup similar to the central pacemaker SCN, uncovering the roles of the peripheral clock in the rhythmic physiology has been an emerging goal in chronobiology. Glucocorticoid (GC) is a multifunctional adrenal steroid hormone that shows a robust circadian rhythm. The daily GC rhythm has long been thought to be governed by the SCN via the hypothalamus-pituitary-adrenal neuroendocrine axis. Recent findings, however, indicate that multiple regulatory mechanisms, including the adrenal intrinsic mechanism by the peripheral...
As one of the evolutionary oldest parts of the brain, the diencephalon evolved to harmonize changing environmental conditions with the internal state for survival of the individual and the species. The pioneering work of physiologists and psychologists around the middle of the last century clearly demonstrated that the hypothalamus is crucial for the display of motivated behaviors, culminating in the discovery of electrical self-stimulation behavior and providing the first neurological hint accounting for the concepts of reinforcement and reward. Here we review recent progress in understanding the role of the lateral hypothalamic area in the control of ingestive behavior and the regulation of energy balance. With its vast array of interoceptive and exteroceptive afferent inputs and its equ...
We explore the structure of a new family gauge symmetry U(3) and show its experimental signatures to search for. U(3) gauge bosons obviate an unwelcome deviation of the charged lepton mass formula with the running masses from that with the pole masses. The current structure of this model leads to flavor number violations via exchange of extra gauge bosons. We obtain bounds on the masses of the gauge bosons from rare kaon decay searches and muonium-antimuonium oscillation searches. We propose attractive signatures at LHC and lepton colliders and discuss feasibility of their discovery.
The principle of conservation and transferability of chemical bonds explains the recent discovery by extended x-ray absorption fine-structure measurements of two unequal anion-cation bond lengths R/sub A/C and R/sub B/C in A/sub x/B/sub 1-x/C zinc-blende semiconductor alloys despite the close adherence of the lattice constant to the average value (Vegard rule). This bond alternation, manifested as a structural distortion to a local chalcopyrite coordination around the anions, explains also most of the observed optical bowing in semiconductor alloys.
The principle of conservation and transferability of chemical bonds explains the recent discovery by extended x-ray absorption fine-structure measurements of two unequal anion-cation bond lengths R/sub A/C and R/sub B/C in A/sub x/B/sub 1-x/C zinc-blende semiconductor alloys despite the close adherence of the lattice constant to the average value (Vegard rule). This bond alternation, manifested as a structural distortion to a local chalcopyrite coordination around the anions, explains also most of the observed optical bowing in semiconductor alloys.
Abstract Over the last decade, the environmental sciences have witnessed an incredible movement towards the utilization of high-throughput molecular tools that are capable of detecting simultaneous changes of hundreds, and even thousands, of molecules and molecular components after exposure of organisms to different environmental stressors. These techniques have received a great deal of attention because they not only offer the potential to unravel novel mechanisms of physiological and toxic action but are also amenable to the discovery of biomarkers of exposure and effects. In this article, we review the state of knowledge of one of these tools in ecotoxicological research: proteomics. We summarize the state of proteomics research in fish, and follow with studies conducted with aquatic in...
The Beyond the Standard Model Working Group discussed a variety of topics relating to exotic searches at current and future colliders, and the phenomenology of current models beyond the Standard Model. For example, various supersymmetric (SUSY) and extra dimensions search possibilities and constraints are presented. Fine-tuning implications of SUSY searches are derived. The implications of Higgs (non)-discovery are discussed, as well as the program HDECAY. The individual contributions are included seperately. Much of the enclosed work is original, although some is reviewed.
Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGy-related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of au...
The founding of the Hanford Engineering Works to produce plutonium is described. The 45-year defense mission has now been replaced with a peaceful mission, that of being the first site for massive cleanup of the 45-year nuclear waste. In order to establish a remedial investigation and feasibility plan, a process of discovery named the Technical Baseline Report must be performed; the task of this process is to discover all that is known about a proposed cleanup site (what the waste was, where did it go). When none of the documentation can answer the question, oral history is utilized. Some of the problems associated with the conduct of oral history interviews are described, particularly Hanford`s legacy of secrecy.
The phase transition is a performance measure of the sparsity-undersampling tradeoff in compressed sensing (CS). This letter reports, for the first time, the existence of an exact phase transition for the $\\ell_1$ minimization approach to the complex valued CS problem. This discovery is not only a complementary result to the known phase transition of the real valued CS but also shows considerable superiority of the phase transition of complex valued CS over that of the real valued CS. The results are obtained by extending the recently developed ONE-L1 algorithms to complex valued CS and applying their optimal and iterative solutions to empirically evaluate the phase transition.
We construct the quantum mechanical field operator of the two-dimensional Liouville theory in a finite box. This leads us to the discovery of a new type of triangle relation which does not reduce to the already known ones. We apply our result to the construction of the string model in an arbitrary number of space-time dimensions D. We show that there are no tachyons in -infinite1, which is a strong-coupling region for the Liouville field theory. (orig.).
An overview of current concepts on neuroinflammation and on the dialogue between neurons and non-neuronal cells in three important infections of the central nervous systems (rabies, cerebral malaria, and human African trypanosomiasis or sleeping sickness) is here presented. Large numbers of cases affected by these diseases are currently reported. In the context of an issue dedicated to Camillo Golgi, historical notes on seminal discoveries on these diseases are also presented. Neuroinflammation is currently closely associated with pathogenetic mechanisms of chronic neurodegenerative diseases. Neuroinflammatory signaling in brain infections is instead relatively neglected in the neuroscience community, despite the fact that the above infections provide paradigmatic examples of alterations o...
The discovery of nearly sixty molecules, often unstable or complexes, in the interstellar space has been one of the greatest surprises of contemporary astronomy. We may, indeed, be surprised that molecules having up to 13 atoms might be synthetized in an extremely diluted space and at a very low temperature. That these molecules are, most of all, organic molecules is another astonishing subject, at least for the non-specialist. The interstellar molecule formation is indeed well understood nowadays, at least for the simplest ones. This article takes stock of interstellar chemistry which is essentially an ionic chemistry very different from laboratory chemistry.
/sup 99m/Tc biliary imaging was performed on a 34-year-old woman who was being investigated for suspected cholelithiasis. A left-sided liver was detected. On subsequent radionuclide imaging, partial visceral situs inversus and asplenia were demonstrated. Extensive roentgenographic investigation, ECG, echocardiogram, and laparotomy confirmed the radionuclide findings. Asplenia syndrome may exist without cardiovascular abnormalities and thus be undiscovered. Radionuclide imaging is important in the diagnosis of this syndrome.
CERN, DESY, Fermilab and SLAC have joined forces to build INSPIRE, the next-generation HEP information platform offering innovative tools for information discovery and communication. Representing a natural community-based evolution of SPIRES, INSPIRE provides fast access to the entire body of HEP literature. As a subject repository it will host fulltexts of preprints, Open Access journal articles and supplementary material like conference slides and multimedia, enabling novel text- and data mining applications. In the spirit of Web2.0 INSPIRE will also supply tools for collaboration and user-enriched content.
Software to aid the distribution and coordination of tasks between different processors was developed to distribute applications written in Fortran. This development led to the discovery of problems unique to Fortran and to interesting practical solutions. Two graphical applications were distributed to a variety of machines and machine pairs: CDC 7600-LSI/11, CRAY-LSI/11, VAX 11/780, and Apollo. These distributions pointed out several parameters such as the use of Fortran COMMON, communication parameters, and processing capabilities that can affect the successful distribution of applications.
We present the case of a 12-year-old girl who presented with a pathological fracture through a benign-appearing osteolytic lesion that was presumed to represent fibrous dysplasia. The fracture healed, and over the next 2.5 years there was further refracturing and healing with progressive osteolysis. A biopsy was performed and revealed Ewing's sarcoma. The disease was locally controlled by neoadjuvant chemotherapy and radiation therapy. The patient is disease free with excellent function 6 years following the discovery of the lesion. We illustrate and discuss the sequence of events. (orig.)
Mass spectrometry was instrumental in the discovery of the fullerenes and the characterization of their special structure (truncated icosahedron). High resolution and high sensitivity mass spectrometry in combination with a crossed molecular beam/electron beam ion source is used here to study a further, very unique property of singly and multiply charged fullerene ions (up to Z=7), i.e. their strong resilience towards decomposition via sequential C_2 evaporation and via Coulomb explosion, respectively. (author).
integrates multiple fisheries information systems to obtain a view of U.S. freshwater fish distribution. Information about NFDI National Framework for Early Detection, Rapid...
Mission losses were incurred by an early warning satellite and a Milstar-2 communications satellite when their launch vehicles malfunctioned, the first, ...
The immediate early gene Arc is emerging as a versatile, finely tuned system capable of coupling changes in neuronal activity patterns to synaptic plasticity, thereby optimizing information...Full Text Available
4) Expand to include client-server interaction (small-scale archive interactions with the goal of evaluating information management capabilities) -- Early ...
instrument is shown in Figure 4-9 The incoming radiation is focused onto ...... An early rocket-borne ultraviolet spectrometer of the Ebert type by ...
Four low activation alloy classes, two austenitic and two ferritic, have been incorporated into the MOTA-1B experiment in the FFTF reactor to provide an early assessment of the suitability of such alloys for reactor service.
The early and precise diagnosis, the prognosis, and the clinical management of multiple sclerosis, remain a considerable challenge. In recent years, the development of novel and powerful proteomic...Full Text Available
This paper reviews the historical aspects of nuclear physics. The scientific aspects of the early transuranium elements are discussed and arms control measures are reviewed. 11 refs., 14 figs. (LSP)
in early 1992 from Lord Corporation, were also found. For both the reflective and absorptive polyurethanes, the fresh paint fluoresces significantly ...
Weaning of beef calves is usually done abruptly and early compared to the natural weaning of the species, and is associated with simultaneous exposure of calves to a range of social and environmental...Full Text Available
Models can be useful at many different levels when considering complex issues such as biological control of mosquitoes. At an early stage, exploratory models are valuable in exploring the characteristics...Full Text Available
Background and AimsIt is well known that genome size differs among species. However, information on the variation and dynamics of genome size in wild populations and on the early...Full Text Available
Two-way communication between the conceptus and the mother during early pregnancy is essential if the pregnancy is to survive. In this review, our primary focus is on biochemical communication...Full Text Available
We propose an approach to achieving early recognition of gesture patterns. Early recognition is a method for recognizing sequential patterns at their earliest stage. Therefore, in the case of gesture recognition, we can get a recognition result for human gestures before the gestures are finished. The most difficult problem in early recognition is knowing when the system has determined the result. Most traditional approaches suffer from this problem, since gestures are often ambiguous. At the start of a gesture, in particular, it is very difficult to determinate the recognition result since insufficient input data have been observed. Therefore, we have improved on the traditional approach by using a self-organizing map.
The purpose of this report is to provide management with performance data on key performance indicators selected from the FFTF Early Warning System performance indicators.
rotor flow field in which the main rotor operates. The majority of ..... early separation predicted by their CFD code was ...... Airfoil, AGARD Fluid Dynamics Panel ...
A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes....Full Text Available
Specialized olfactory lobe glomeruli relating to sexual or caste differences have been observed in at least five orders of insects, suggesting an early appearance of this trait in insect evolution....Full Text Available
PurposeEarly detection of appendicitis has increased due to development of computed tomography and ultrasonography, yet we are frequently meeting complicated appendicitis, including...Full Text Available
BackgroundAutofluorescence bronchoscopy is more sensitive than conventional bronchoscopy for detecting early airway mucosal lesions. Decreased specificity can lead...Full Text Available
Documents an early American industrial process of making blast furnace coke using techniques and equipment from the 19th century. Photographed at Bretz, WV.
Mutations in the Drosophila gene drop-dead (drd) result in early adult lethality and neurodegeneration, but the molecular identity of the drd...Full Text Available
Experience gained with a wide variety of missile injuries of the brain is presented. Clinical signs and intracranial pressure (ICP) studied in the early post-injury period have been correlated with...Full Text Available
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 ...
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
Calgary-based TAG Oil is an exploration company that manages 4.1 million acres of major producing oil and gas fields in New Zealand. The enormous Maui field, with 4 tcf of natural gas in place, has dominated the gas market in New Zealand by meeting nearly 90 per cent of the country's energy demand at costs much lower than world prices. However, the maturing field is in decline and will cease production by 2008. New gas field discoveries will only meet 60 per cent of the country's energy requirements for 5 additional years. Unless new large reserves of gas are discovered, the supply and demand situation will get worse. Lead time to place new production on-stream requires 5 to 10 years, which creates a large supply gap over the next decade. Public resistance to coal-fired power plants, new hydroelectric dams and nuclear power has left the country with no viable alternative to natural gas. TAG Oil has taken this unique opportunity to create value when gas demand is at ...
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 ...
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 ...
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 drug delivery 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...
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...
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...
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 ...
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...
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...
The 5'-terminal structures of human adenovirus type 2 (Ad2) early region 2 (E2) mRNA were investigated. The E2 transcription unit has several interesting properties, including the presence of a TATA-like...Full Text Available
Epulopiscium sp. type B is an enormous intestinal symbiont of the surgeonfish Naso tonganus. Intracellular offspring production in Epulopiscium shares features with endospore formation. Here, we characterize the spoIIE homolog in Epulopiscium. The timing of spoIIE gene expression and presence of interacting partners suggest that the activation of ?(F) occurs early in Epulopiscium offspring development. PMID:21398534
Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation...Full Text Available
Three transcription units are present in the adenovirus type 2 region EII. Transcription units EIIaE and EIIaL encode the mRNA for the 72,000-dalton DNA binding protein, early and late in the lytic...Full Text Available
...notice de en es fr it nl European Commission Research Index aeronews All keywords Index feedback The number of documents that contain the keyword aeronews is: 1 EU Transport lsquo;AERONEWSrsquo; -good news for early detection of microdamage European Commission - lsquo;AERONEWSrsquo; -good news for early detection of microdamage ...
Recent nucleosynthesis calculations of Type II supernovae using advanced neutrino transport determine that the early neutrino winds are proton-rich. However, a fraction of the ejecta emitted at the same time is composed of neutron-rich pockets. In this paper we calculate the nucleosynthesis contribution from the neutron-rich pockets in the hot convective bubbles of a core-collapse supernova and show that they do not contribute significantly to the total nucleosynthesis.
A large inguino-scrotal hernia was detected in the early phase of a radionuclide bone scan performed for evaluation of a femoral neck fracture not visualized on plain x-rays. The patient was administered 1 GBq of Scrotal scintigraphy using "9"9"mTc-MDP and a regional three-phase bone scan of the pelvis, hips and proximal femora was obtained on the gamma camera. Copyright (1999) Blackwell Science Pty Ltd
BackgroundApoptosis is a major mode of hematological tumor death after radiation. Early detection of apoptosis may be beneficial for cancer adaptive treatment. 99mTc-HYNIC-annexinV...Full Text Available
The non-invasiveness of autofluorescence technology may reduce sampling error and time delay for histopathology diagnosis. We establish biophotonic methods and guidelines to visualize and interpret early epithelial tissue changes that signify disease. Flexible and rigid fiber endomicroscopy instrumentation design parameters feasible for translation towards clinical use are in development.
DescriptionThe overall aim of this application is to examine experimentally environmental influences on the pattern of senescence in birds. We plan to experimentally uncouple chronological age and reproductive effort and examine their effects on reproductive performance and lifespan. We also plan to examine experimentally how these relationships are influenced by nutritional conditions during early development. We will combine the organismal fitness measures of lifespan and reproductive performance with me [continued...
The impact of a single seizure on cognition remains controversial. We hypothesized that a single early life seizure (sELS) on rat post-natal day (P) 7 would alter only hippocampal-dependent...Full Text Available
Elution profiles of total lipoproteins, apolipoprotein B (apoB) concentrations in lipoproteins, and plasma triglyceride (TG) levels were examined in early-, late-, and non-lactating cows. Additionally, arteriovenous (A-V) differences were also measured to elucidate the uptake of TG and apoB-containing lipoproteins in mammary gland. Non-lactating cows showed three major peaks corresponding to triglyceride-rich lipoprotein (TRL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fraction, whereas both early- and late-lactating cows revealed two peaks corresponding to TRL and HDL. The peak area of TRL in early- and late-lactating cows were significantly (p < 0.05) smaller than that in non-lactating cows. The plasma TG levels and apoB-48 concentrations of TRL in early- and late-lactating cows were also significantly (p < 0.01) lower. Furthermore, early lactating ...
Childhood anxiety is impairing and associated with later emotional disorders. Studying risk factors for child anxiety may allow earlier identification of at-risk children for prevention efforts. This study applied an ecological risk model to address how early childhood anxiety symptoms, child temperament, maternal anxiety and depression symptoms, violence exposure, and sociodemographic risk factors predict school-aged anxiety symptoms. This longitudinal, prospective study was conducted in a representative birth cohort (n = 1109). Structural equation modeling was used to examine hypothesized associations between risk factors measured in toddlerhood/preschool (age = 3.0 years) and anxiety symptoms measured in kindergarten (age = 6.0 years) and second grade (age = 8.0 years). Early child risk factors (anxiety symptoms and temperament) emerged as the most robust predictor for both parent-and child-reported anxiety outcomes and mediated the effects ...
ObjectivesA national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were...Full Text Available
Abstract Overall Numbers Small, But Study Finds SSRI Exposure, Autism Link Additional Drug Safety, Efficacy Data Needed for Pediatric Bipolar Disorder SGA Safety and Efficacy in Children and Adolescents Aripiprazole Safety and Tolerability for Irritability in Autism No Lisdexamfetamine Effect on Sleep Disturbances in Children With ADHD Sickle Cell Disease With Comorbid Depression Homeopathy in Psychiatry Manic Symptoms Induced by Marijuana in a Healthy Adolescent New Warnings Safety Labeling Changes
Abstract Clonidine Extended Release Augmentation of Psychostimulants in ADHD ADHD a Risk Factor for Substance Abuse; Cognitive Deficits Not a Predictor Commentary on Kollins et al.; Clonidine XR Augmentation for ADHD Pharmacologic Treatment of Childhood Insomnias Effects of Guanfacine Extended Release on Alertness in ADHD Long Term ADHD Drug Treatment Bipolar Disorder Rates Similar Across Selected Countries Group CBT Alone or Group CBT Plus SSRIs in Childhood Anxiety Resolution of Quetiapine-Induced Oral Dyskinesia From the FDA
A previously healthy young man experienced several episodes of syncope while being treated with tenofovir, emtricitabine and nevirapine initiated during primary HIV-1 infection. Symptoms disappeared after discontinuation of antiretroviral therapy and we suggest that syncope may be a side effect to one of the three antiretroviral drugs that has not been described previously.
Human serum albumin (HSA) has two primary binding sites for drug molecules. These sites selectively bind different dansylated amino acid compounds, which—due to their intrinsic fluorescence—have...Full Text Available
σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available
... 03/08/2011 Professor named Chair at Epworth Hospital Professor Nilmini Wickramasinghe from the College of Business at RMIT University has been named Epworth Chair, Health Information Management , by Epworth HealthCare. 26/07/2011 Study investigates drug-free relief for tension headaches As Australia marks its first National Pain Week ...
A pro-drug 8 of a synthetic analog 7 is more active in its anti-proliferative activity against human breast cancer MDA-MB-231 cells possessing high Catechol-O-methyltransferase...Full Text Available
Loss of the sense of smell can be easily confirmed in any physician's office by having the patient try to identify various odors. The etiology of anosmia can be extremely varied, including nasopharyngeal disorders such as rhinitis and tumors; neurologic conditions such as head trauma, neoplasms, vascular lesions and infections of the central nervous system; viral infections; familial and congenital disorders; drugs; industrial exposure; endocrine diseases, and several other disorders. The prognosis of anosmia is guarded, and its treatment depends on the etiology.
...Resort and Convention Center, National Harbor, Maryland, USA September 18-20, 2011 XX HELSINKI DRUG RESEARCH CONGRESS Helsinki, Finland October 23-27, 2011 2011 AAPS Annual Meeting and Exposition Washington Convention Center Washington, DC June 26-29 2012 10th International Symposium on Pharmaceutical Sciences Ankara, Turkey Printer-friendly version Home | Elsevier ...
Simultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid...Full Text Available
Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural...Full Text Available
BackgroundIntermittent preventive treatment of malaria during pregnancy (IPTp) is a key intervention in the national strategy for malaria control in Tanzania. SP, the current drug...Full Text Available
The aim of this study was to assess the prevalence and correlates of disclosure to network members of being hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)-infected among injecting dyads of infected injection drug users (IDUs) in Budapest, Hungary and Vilnius, Lithuania,. Multivariate generalized estimating equations (GEE) were used to assess associations. Very strong infection disclosure norms exist in Hungary, and HCV disclosure was associated with using drugs and having sex within the dyad. Non-ethnic Russian IDUs in Lithuania were more likely to disclose HCV infection to non-Roma, emotionally close and HCV-infected network members, and to those with whom they shared cookers, filters, drug solutions or rinse water or got used syringes from, and if they had fewer non-IDU or IDU network members. Ethnic Russian Lithuanian IDUs were more likely to disclose HCV if they had higher disclosure attitude and ...
...Correction Discussion Editorial Letter Opinion Review Short Note Technical Note Special Issue all A Systematic Development Method for Rational Drug Design Advances in Molecular Electronic Structure Calculations Algorithms and Molecular Sciences Antimicrobial Agents Application of Density Functional Theory Applications of Density Functional Theory Applications of Molecular Dynamics Atoms in Molecules ...
In order to better understand the molecular mechanisms of human hair growth control and to test hair growth-modulatory drugs, appropriate in vitro models are required. Here, we report the long-term...Full Text Available
BackgroundHepatitis C virus (HCV) infection is the leading cause of chronic hepatitis which progresses to hepatocellular carcinoma (HCC) afflicting > 170 million people worldwide....Full Text Available
A recently developed neutron diagnostic probe system has the potential to satisfy a significant number of van-mobile and fixed- portal requirements for nondestructive verification of sealed munitions and detection of contraband explosives and drugs. The probe is based on a unique associated-particle sealed-tube neutron generator (APSTNG) that interrogates the object of interest with a low-intensity beam of 14-MeV neutrons generated from the deuterium-tritium reaction and that detects the alpha-particle associated with each neutron. Gamma-ray spectra of resulting neutron inelastic scattering and fission reactions identify nuclides associated with all major chemicals in chemical warfare agents, explosives, and drugs, as well as many pollutants and fissile and fertile special nuclear material. Flight times determined from determined from detection times of the gamma-rays and alpha-particles yield a separate tomographic image of each identified ...
BackgroundIn Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect....Full Text Available
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of ...
Located approximately 350 km east of Newfoundland, on the eastern edge of the Jeanne d'Arc Basin, and approximately 50 km from both the Terra Nova and Hibernia oilfields, the White Rose oilfield is considered the main oil producing basin off the eastern coast of North America. Husky Oil is very active in the region and holds almost 32 per cent net working interest in the Significant Discovery License areas in the Jeanne d'Arc basin. The development of an economically significant oil discovery in the White Rose Significant Discovery Area is being proposed jointly by Husky Oil and Petro-Canada. It is estimated that the project would enable the recovery of an estimated 36 million cubic meters (230 million barrels) of recoverable oil in this area that covers approximately 40 square kilometers. The operators propose to use a ship-shaped floating production, storage and offloading (FPSO) facility which could ...
The paper investigates early Soviet policies regarding the institution of waqf (charitable endowment) in Turkestan, questioning the issue of the post-colonial character of the early Soviet administration. After taking into consideration practices related to waqf management in modern Muslim states and European colonial empires, the paper briefly describes the tsarist administrative approach to the issue. We then address the ambiguity inherent in Soviet policies on waqf requisition and restitution during Civil War years. In the section that follows we deal with different groups of Muslim intellectuals that attempted to use the Soviet state in their mutual struggle over authority in Central Asian society and describe the creation and functioning of the bureaucracies responsible for managing w...
This longitudinal study examined a model of early school achievement in reading and math, as it varies by socioeconomic context, using data from the NICHD Study of Early Child Care and Youth Development. A conceptual model was tested that included features of family stress, early parenting, and school readiness, through both a single-group analysis and also a multiple-group analysis. Latent profile analysis was used to identify subgroups of more advantaged and less advantaged families. Family stress and parenting were shown to operate differently depending on the socioeconomic context, whereas child-based school readiness characteristics were shown to operate similarly across socieodemographic contexts. Implications for intervention are discussed.
Six patients with diskitis following lumbar disk surgery were investigated by Computed Tomography (CT). Four patients underwent CT in a rather early phase of the disease (5-37 days after the onset of the symptoms): a posterior paravertebral fluid collection was always recognized, while the plain film was normal. Later on (2-4 months), the classical signs of diskitis were evident, with both CT and the plain film. The collection was always present at CT. A reintervention, performed on 3 patients, revealed the purulent content of the collections. It seems reasonable to suggest a relationship between the collection and the subsequent diskitis; the collection is probably an early sign of the disease. Its detection is of grat value, because it could allow an immediate and adequate therapy. The authors stress the usefulness of performing CT in an early phase on this kind of symptomatic patients.
There are no specific diagnostic tests or a gold standard method for measuring disease activity and outcome in spondyloarthropathies (SpA). Many different methods have been developed to assess the signs and symptoms in SpA. The aim of this study was to evaluate the value of scintigraphy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Bath Ankilosing Spondylitis Disease Activity Index (BASDAI) in the evaluation of disease activity in early axial SpA diagnosed with magnetic resonance imaging (MRI). Thirty early MRI-positive axial SpA patients (23 males, 7 females) with a median age of 35 (18?55) years and a median duration of inflammatory low back pain of 24 (8?60) months were included in the study. In the patients with sacroiliitis, the sensitivity, specificity, and pos...
The early diagnosis of such disorders is of major importance because, in most cases, severe consequences can only be averted by early treatment. The value of magnetic resonance imaging (MRI) in many orthopaedic and traumatological conditions is generally accepted. The value of MRI in this particular field is illustrated by typical case reports on common clinical problems [Deutsch] Der Fruehdiagnose von Erkrankungen des Kindes- und Jugendalters kommt grosse Bedeutung zu, da oftmals nur durch eine daraus resultierende Fruehbehandlung schwerwiegende Folgen vermieden werden koennen. Die Kernspintomographie (Magnetresonanztomographie=MRT) ist in zahlreichen orthopaedischen-traumatologischen Fragestellungen bereits etabliert. An ausgewaehlten Fallbeispielen haeufiger klinischer Problemstellungen soll in der vorliegenden Arbeit der Stellenwert der MRT dargestellt werden. (orig.)
Climate variability greatly affects animals through direct and indirect effects. Animals with slow reproductive adaptation to ecological changes such as large mammals are likely to have evolved mechanisms to anticipate early such impacts of climate variability on the environment. One of the adaptive mechanisms between reproductive costs and benefits in mammals affects parental investment through biases in sex ratio. Deer might be likely to show an early detection of climate variability because conception takes place in early autumn, but the main raising cost in deer concerns lactation, which takes place at the end of the following spring. The aim of this paper is to assess whether there is a relationship between global indices of climate variability such as El Ni?o-Southern Oscillation (EN...
Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects premature newborns. This disease often has a rapid onset with few, if any, antecedent signs that can be used to reliably predict its occurrence. Its rapid onset and progression to death, as well as its severe morbidity when the infant survives, begs for early diagnostic tools that may be used in determining those infants who would be at greatest risk for development of the disease and for whom early preventative measures could be targeted. Although studies have suggested efficacy of several techniques such as breath hydrogen, inflammatory mediators in blood, urine or stool, and genetic markers, these all have drawbacks limiting their use. The application of newly developed "omic" approaches may provide biomarkers for early diagnosis and targeted prevention of this disease. PMID:19190533
Abstract The Hippo pathway is an evolutionally conserved protein kinase cascade involved in regulating organ size in vivo and cell contact inhibition in vitro by governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is linked to cancer development. Its first core kinase Warts was identified in Drosophila more than 15 years ago, but it gained much attention when other core components of the pathway were identified 8 years later. Major discoveries of the pathway were made during past several years. The core kinase components Hippo, Salvador, Warts, and Mats in the fly and Mst1/2, WW45, Lats1/2, and Mob1 in mammals phosphorylate and inactivate downstream transcriptional co-activators Yorkie in the fly, Yes-associated protein (YAP) and transcriptional co-activator with ...
Motivated by the discovery of superconductivity in alkali and alkaline earth fullerides, this program was undertaken both to understand the nature of and expand the range of materials demonstrating superconductivity. The first approach involved attempts to modify the fullerene cage by incorporating heteroatoms in the structure and the preparation and photophysical properties of nitrogen and sulfur doped fullerenes were studied in detail. The second approach involved examining the stoichiometry and effect of preparative conditions on the behavior of alkali, alkaline earth, lanthanide and mixed ion fullerides. In particular, the authors have elaborated on a technique for making such salts using liquid ammonia or aliphatic amines as solvents. Thirdly, modeling studies were undertaken to predict the properties of heterohedral fullerines and metal - C60 complexes, and theoretical guidelines were developed for understanding the reactivity of the fullerene cage to common ...
In light of the recent discovery of the importance of the isovector EMC effect for the interpretation of the NuTeV determination of sin^2 theta_W, it seems timely to reassess the central value and the errors on this fundamental Standard Model parameter derived from the NuTeV data. We also include earlier work on charge symmetry violation and the recent limits on a possible asymmetry between s and \\bar{s} quarks. With these corrections we find a revised NuTeV result of sin^2 theta_W = 0.2232 \\pm 0.0013(stat) \\pm 0.0024(syst), which is in excellent agreement with the running of sin^2 theta_W predicted by the Standard Model.
Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, na...
The interaction energies between the different types of bases of a single strand of DNA molecule have been calculated. Using these original values of energies the harmonic behavior of a number of base patterns of DNA has been studied. In view of the great interest aroused by the discovery of the role of the telomere segment of the DNA in the replication process and its possible link with the aging process, we have investigated, with simple models, the harmonic behavior of the telomeric pattern of bases as well as the thermodynamic response in the biological system. With these results a conclusion on the probable role of the telomeric pattern on aging has also been drawn. Here the calculated values of harmonic frequencies of the telomeric pattern of bases and of other possible patterns show that the telomeric pattern is associated with the highest vibrational frequency among all patterns of base combinations at the replication end of DNA. This seems to suggest that ...
With the exception of the 1945 Hiroshima and Nagasaki nuclear weapon explosions and the 1986 Tchernobyl reactor accident, most of the radiation accidents concerns the medical and the traditional industrial sectors. The seriousness of the accident is directly function of the absorbed dose. The paper, first, gives the definition of a radiologic accident with its specific criteria and pathological manifestations. Then, some famous historical accidents are reviewed from the discovery of X-rays to recent acute irradiations due to the careless manipulation of radiation sources. From this analysis, three main causes are put forward: the dysfunction of nuclear medicine apparatuses, the victims` lack of training and knowledge of the risks, and the non-identification or the loss of radiation sources. (J.S.). 1 photo.
Males and females display differences in physiology, behaviour and susceptibility to many diseases. Genome-wide transcription profiling studies have uncovered large-scale sex differences in autosomal gene expression in somatic tissues that are thought to underlie such 'sexual dimorphisms'. Because males and females differ genetically mainly in their sex chromosome complement, most sex differences can be traced back to the X and Y chromosomes. Although sex hormones are usually considered the main architects of sexual dimorphisms, recent studies have demonstrated that sex chromosomes can also induce sex differences in somatic gene expression in the absence of hormonal differences. The recent discovery of epigenetic sex differences that are not hormone-induced brings us closer to understandin...
Wireless mesh networks can provide low-cost solutions for extending the reach of wireless access points by using multi-hop routing over a set of stationary wireless routers. The routing protocol for these networks may need to address quality considerations to meet the requirements of the user. In this paper, we present a quality based routing protocol for wireless mesh networks that tries to maximize the probability of successful transmissions while minimizing the end-to-end delay. The proposed routing protocol uses reactive route discoveries to collect key parameters from candidate routes to estimate the probability of success and delay of data packets transmitted over them. To achieve accurate route quality assessments, a new route quality metric is proposed that uses performance models ...