WorldWideScience

Sample records for activity potential clinical

  1. Serum activity of platelet-activating factor acetylhydrolase is a potential clinical marker for leptospirosis pulmonary hemorrhage.

    Directory of Open Access Journals (Sweden)

    Junwei Yang

    Full Text Available Pulmonary hemorrhage has been recognized as a major, often lethal, manifestation of severe leptospirosis albeit the pathogenesis remains unclear. The Leptospira interrogans virulent serogroup Icterohaemorrhagiae serovar Lai encodes a protein (LA2144, which exhibited the platelet-activating factor acetylhydrolase (PAF-AH activity in vitro similar to that of human serum with respect to its substrate affinity and specificity and thus designated L-PAF-AH. On the other hand, the primary amino acid sequence of L-PAF-AH is homologous to the alpha1-subunit of the bovine brain PAF-AH isoform I. The L-PAF-AH was proven to be an intracellular protein, which was encoded unanimously and expressed similarly in either pathogenic or saprophytic leptospires. Mongolian gerbil is an appropriate experimental model to study the PAF-AH level in serum with its basal activity level comparable to that of human while elevated directly associated with the course of pulmonary hemorrhage during severe leptospirosis. Mortality occurred around the peak of pulmonary hemorrhage, along with the transition of the PAF-AH activity level in serum, from the increasing phase to the final decreasing phase. Limited clinical data indicated that the serum activity of PAF-AH was likely to be elevated in the patients infected by L. interrogans serogroup Icterohaemorrhagiae, but not in those infected by other less severe serogroups. Although L-PAF-AH might be released into the micro-environment via cell lysis, its PAF-AH activity apparently contributed little to this elevation. Therefore, the change of PAF-AH in serum not only may be influential for pulmonary hemorrhage, but also seems suitable for disease monitoring to ensure prompt clinical treatment, which is critical for reducing the mortality of severe leptospirosis.

  2. Antioxidative activity of high-density lipoprotein (HDL: Mechanistic insights into potential clinical benefit

    Directory of Open Access Journals (Sweden)

    Fernando Brites

    2017-12-01

    Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target.

  3. BADERI: an online database to coordinate handsearching activities of controlled clinical trials for their potential inclusion in systematic reviews.

    Science.gov (United States)

    Pardo-Hernandez, Hector; Urrútia, Gerard; Barajas-Nava, Leticia A; Buitrago-Garcia, Diana; Garzón, Julieth Vanessa; Martínez-Zapata, María José; Bonfill, Xavier

    2017-06-13

    Systematic reviews provide the best evidence on the effect of health care interventions. They rely on comprehensive access to the available scientific literature. Electronic search strategies alone may not suffice, requiring the implementation of a handsearching approach. We have developed a database to provide an Internet-based platform from which handsearching activities can be coordinated, including a procedure to streamline the submission of these references into CENTRAL, the Cochrane Collaboration Central Register of Controlled Trials. We developed a database and a descriptive analysis. Through brainstorming and discussion among stakeholders involved in handsearching projects, we designed a database that met identified needs that had to be addressed in order to ensure the viability of handsearching activities. Three handsearching teams pilot tested the proposed database. Once the final version of the database was approved, we proceeded to train the staff involved in handsearching. The proposed database is called BADERI (Database of Iberoamerican Clinical Trials and Journals, by its initials in Spanish). BADERI was officially launched in October 2015, and it can be accessed at www.baderi.com/login.php free of cost. BADERI has an administration subsection, from which the roles of users are managed; a references subsection, where information associated to identified controlled clinical trials (CCTs) can be entered; a reports subsection, from which reports can be generated to track and analyse the results of handsearching activities; and a built-in free text search engine. BADERI allows all references to be exported in ProCite files that can be directly uploaded into CENTRAL. To date, 6284 references to CCTs have been uploaded to BADERI and sent to CENTRAL. The identified CCTs were published in a total of 420 journals related to 46 medical specialties. The year of publication ranged between 1957 and 2016. BADERI allows the efficient management of handsearching

  4. Peptide inhibitor of complement C1 (PIC1, a novel suppressor of classical pathway activation: mechanistic studies and clinical potential

    Directory of Open Access Journals (Sweden)

    Julia A Sharp

    2014-08-01

    Full Text Available The classical pathway of complement plays multiple physiological roles including modulating immunological effectors initiated by adaptive immune responses as well as an essential homeostatic role in the clearance of damaged self-antigens. However, dysregulated classical pathway activation is associated with antibody-initiated, inflammatory diseases processes like cold agglutinin disease (CAD, acute intravascular hemolytic transfusion reaction (AIHTR and acute/hyperacute transplantation rejection. To date, only one putative classical pathway inhibitor, C1 esterase inhibitor (C1-INH, is currently commercially available and its only approved indication is for replacement treatment in hereditary angioedema (HAE, which is predominantly a kinin pathway disease. Given the variety of disease conditions in which the classical pathway is implicated, development of therapeutics that specifically inhibit complement initiation represents a major unmet medical need. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement. In vitro studies have demonstrated that these Peptide Inhibitors of Complement C1 (PIC1 bind to the collagen-like region of the initiator molecule of the classical pathway, C1q. PIC1 binding to C1q blocks activation of the associated serine proteases (C1s-C1r-C1r-C1s and subsequent downstream complement activation. Rational design optimization of PIC1 has resulted in the generation of a highly potent derivative of fifteen amino acids. PIC1 inhibits classical pathway mediated complement activation in ABO incompatibility in vitro as well as inhibiting classical pathway activation in vivo in rats. This review will focus on the pre-clinical development of PIC1 and discuss its potential as a therapeutic in antibody-mediated classical pathway disease, specifically AIHTR.

  5. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare

    2009-07-01

    cytotoxic and inhibits, in a dose dependent fashion, the synthesis of polyomavirus DNA in the infected cell. Furthermore, this inhibition is observed at non cytotoxic concentrations of the drug. Our data imply that cyto-toxicity may be attributed to the membrane damage caused by the drug and that the transfer of polyomavirus from the endoplasmic reticulum to the cytoplasm may be hindered. In conclusion, the cytotoxic and antiviral properties of resveratrol make it a potential candidate for the clinical control of proliferative as well as viral pathologies.

  6. Acetyl aspartic acid, a novel active ingredient, demonstrates potential to improve signs of skin ageing: from consumer need to clinical proof.

    Science.gov (United States)

    Mavon, A

    2015-10-01

    The megatrend of population ageing is leading to a growing demand for "anti-ageing" treatments, especially to prevent or treat skin ageing. Facing an increasing offer, consumers are choosing more and more skin care products supported by a scientific rationale, active ingredients and clinical proof of efficacy. Considering consumer expectations, this research led to the discovery of acetyl aspartic acid (A-A-A), a novel active ingredient to improve sagging skin and loss of skin firmness. This supplement is featuring seven manuscripts aiming at presenting the research and investigations from consumer insights, discovery of A-A-A, its in vitro activity confirmation, safety assessment, formulation and its dermal absorption to the clinical proof of efficacy, investigated through two pilots' double bind randomized and placebo controlled studies on photo-aged skin. This extensive research enabled us to discover A-A-A, as an active ingredient with potential to repair sign of skin ageing and supported by clinical proof of efficacy. This active ingredient will be soon launched in a commercial innovative skin care range, delivering desirable anti-wrinkle and skin lifting benefits. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  7. Hemolytic activity and production of germ tubes related to pathogenic potential of clinical isolates of Candida albicans

    Directory of Open Access Journals (Sweden)

    MELYSSA FERNANDA NEGRI

    2010-06-01

    Full Text Available ABSTRACT We assessed the virulence factor profile and in vitro antifungal susceptibility of 27 hospital isolates of C. albicans; 19 of these were from infections (16 urinary and three blood, and the other eight were isolated from sites of colonization (two from hands of health professionals, and six from central venous catheters. The virulence factors assayed were germ tube formation and production of extracellular products (hemolysins, proteinases, and phospholipases. Susceptibility to fluconazole, itraconazole, voriconazole and amphotericin B was determined by E-test. Regarding the virulence factors, the infection isolates produced significantly more hemolysin and germ tubes than the colonization isolates (p<0.05. There were no significant differences in the production of other factors between isolates from the two sources (p>0.05. Amphotericin B showed the lowest minimum inhibitory concentrations for all the isolates. The highest resistance was observed for the azoles, especially in the clinical isolates. These results suggest that the capacity of C. albicans to produce hemolysins and germ tubes may be associated with its pathogenic potential. Colonization isolates may pose a high risk of nosocomial infection, especially when the yeasts show resistance to antifungals. Keywords: Nosocomial infection. Virulence. Candida albicans. Germ tube. Hemolysins. RESUMO Atividade hemolítica e produção de tubos germinativos relacionados ao potencial patogênico de isolados clínicos de Candida albicans O perfil de virulência e o de susceptibilidade in vitro aos antifúngicos de 27 amostras de C. albicans de origem hospitalar foi avaliado, sendo que 19 delas foram isoladas de infecções (16 urinárias e três sanguíneas e as outras oito foram isoladas de colonização (duas de mãos de profissionais da saúde e seis de cateter venoso central. Os seguintes fatores de virulência foram investigados: formação de tubo germinativo e produ

  8. Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies

    Directory of Open Access Journals (Sweden)

    Laith Altaweel

    2009-09-01

    Full Text Available Laith Altaweel, Daniel Sweeney, Xizhong Cui, Amisha Barochia, Charles Natanson, Peter Q EichackerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USAAbstract: Recombinant human activated protein C (rhAPC was developed to reduce excessive coagulant and inflammatory activity during sepsis. Basic and clinical research has suggested these pathways contribute to the pathogenesis of this lethal syndrome and are inhibited by rhAPC. Based in large part on the results of a single multicenter randomized controlled trial, rhAPC was first approved in 2001 by the US Food and Drug Administration (FDA as adjunctive therapy in septic patients with a high risk of death. This was followed closely by approval in Europe, Australia, and New Zealand. At the original FDA review of rhAPC, concerns were raised as to whether a confirmatory trial should be done before final regulatory approval because of concerns that rhAPCs bleeding risk might outweigh its potential benefit during clinical use. Since 2001, continuing basic and clinical research has further elucidated the complex role activated protein C may have in both adaptive and maladaptive responses during sepsis. Moreover, subsequent controlled trials in other types of septic patients and observational studies appear to support earlier concerns that the benefit-to-risk ratio of rhAPC may not support its clinical use. This experience has prompted additional trials presently underway, to define whether treatment with rhAPC as it was originally indicated in septic patients with persistent shock, is safe and effective. Until such trials are complete, physicians employing this agent must carefully consider which patients may be appropriate candidates for rhAPC administration.Keywords: rhAPC, treatment, sepsis

  9. Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

    Directory of Open Access Journals (Sweden)

    Bohonowych Jessica ES

    2011-12-01

    Full Text Available Abstract Background Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF function in a von Hippel-Lindau (VHL independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Methods Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC inhibitor LBH589. Results The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. Conclusions We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.

  10. Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

    International Nuclear Information System (INIS)

    Bohonowych, Jessica ES; Peng, Shuping; Gopal, Udhayakumar; Hance, Michael W; Wing, Shane B; Argraves, Kelley M; Lundgren, Karen; Isaacs, Jennifer S

    2011-01-01

    Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589. The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression

  11. Potential benefits and risks of clinical xenotransplantation

    Directory of Open Access Journals (Sweden)

    Cooper DKC

    2012-07-01

    Full Text Available David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes, neuronal cells (for the treatment of Parkinson's disease, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs

  12. Toxicology and clinical potential of nanoparticles

    Science.gov (United States)

    Yildirimer, Lara; Thanh, Nguyen T.K.; Loizidou, Marilena; Seifalian, Alexander M.

    2011-01-01

    Summary In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports. PMID:23293661

  13. Potential for new technologies in clinical practice.

    Science.gov (United States)

    Burridge, Jane H; Hughes, Ann-Marie

    2010-12-01

    Cost-effective neurorehabilitation is essential owing to financial constraints on healthcare resources. Technologies have the potential to contribute but without strong clinical evidence are unlikely to be widely reimbursed. This review presents evidence of new technologies since 2008 and identifies barriers to translation of technologies into clinical practice. Technology has not been shown to be superior to intensively matched existing therapies. Research has been undertaken into the development and preliminary clinical testing of novel technologies including robotics, electrical stimulation, constraint-induced movement therapy, assistive orthoses, noninvasive brain stimulation, virtual reality and gaming devices. Translation of the research into clinical practice has been impeded by a lack of robust evidence of clinical effectiveness and usability. Underlying mechanisms associated with recovery are beginning to be explored, which may lead to more targeted interventions. Improvements in function have been demonstrated beyond the normal recovery period, but few trials demonstrate lasting effects. Technologies, alone or combined, may offer a cost-effective way to deliver intensive neurorehabilitation therapy in clinical and community environments, and have the potential to empower patients to take more responsibility for their rehabilitation and continue with long-term exercise.

  14. Outcome Assessments in Clinical Trials of Cryptococcal Meningitis: Considerations on Use of Early Fungicidal Activity as a Potential Surrogate Endpoint for All-Cause Mortality

    Science.gov (United States)

    Montezuma-Rusca, Jairo Mauricio; Powers, John H.

    2015-01-01

    Opinion statement Cryptococcal meningitis (CM) is a common disease in resource-challenged settings, with a high mortality within weeks of disease onset. Mortality remains high with current treatments, so more effective interventions are needed to decrease mortality. There has been interest in using the outcome assessment of quantification of fungus from cerebrospinal fluid as a replacement (surrogate) endpoint for all-cause mortality (ACM) as a means of decreasing sample size in randomized clinical trials in CM. To evaluate a biomarker as a potential surrogate endpoint to replace ACM requires several steps. This paper discusses the issues of determining whether the context of a disease is one where a potential surrogate endpoint is rational, the types of outcome assessments that might qualify as potential surrogates, and the process for evaluation of the evidence that a chosen biomarker is a valid replacement for ACM in the given context of use. We then apply those principles to the context of randomized clinical trials of CM. PMID:26306077

  15. Zolpidem, A Clinical Hypnotic that Affects Electronic Transfer, Alters Synaptic Activity Through Potential Gaba Receptors in the Nervous System Without Significant Free Radical Generation

    Directory of Open Access Journals (Sweden)

    Peter Kovacic

    2009-01-01

    Full Text Available Zolpidem (trade name Ambien has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET, pharmacodynamics, structure activity relationships (SAR and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action.

  16. Molecular heterogeneity in glioblastoma: potential clinical implications

    Directory of Open Access Journals (Sweden)

    Nicole Renee Parker

    2015-03-01

    Full Text Available Glioblastomas, (grade 4 astrocytomas, are aggressive primary brain tumors characterized by histopathological heterogeneity. High resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.

  17. Integrative Potential of Architectural Activities

    Science.gov (United States)

    Davydova, O. V.

    2017-11-01

    The architectural activity integrative potential is considered through the combination as well as the organization of necessary universal human and professional, artificial and natural, social and individual architectural activities in the multidimensional unity of its components reflecting and influencing the public thinking with the artistic-figurative language of international communication using experimental form-building, interactive presentations, theatrical and gaming expressiveness to organize an easier contact with the consumer, methods of design and advertising. The methodology is used to reflect the mutual influence of personal and social problems through globalization and identification of their problem in the public, to study the existing methods of the problem solving, to analyze their effectiveness, to search for actual problems and new solutions to them using the latest achievements of technological progress, artistic patterns, creation of a holistic architectural image reflecting the author’s worldview in the general picture of the modern world with its inherent tendencies “Surah” and “entertainment”. The operative communication means in the chain of social experience are developed - the teacher - the trainee - the new educational result used to transmit the updated information in a generalized form, the current and final control through the use of feedback sheets, supporting summaries, info cards, its decisions. The paper considers the study time efficiency due to the organization of the research activity which allows students to obtain a theoretical generalized information (the creator’s limitation) in the process of filling or compiling informative and diagnostic maps that provide the theoretical framework for the creative activity through gaming activity that turns into a work activity which has a diagnosed result.

  18. [Research activity in clinical biochemistry

    DEFF Research Database (Denmark)

    Jorgensen, H.L.; Larsen, B.; Ingwersen, P.

    2008-01-01

    BACKGROUND: Quantitative bibliometric measurements of research activity are frequently used, e.g. for evaluating applicants for academic positions. The purpose of this investigation is to assess research activity within the medical speciality of Clinical Biochemistry by comparing it with a matched...... Clinical Biochemistry, 57 fulfilled the inclusion criteria. Each of these 57 was matched according to medical title with two randomly chosen specialists from other specialities, totaling 114. Using Medline and the Web of Science, the number of publications and the number of citations were then ascertained....... RESULTS: 25% of the 11,691 specialists held a PhD degree or doctoral degree, DMSci, (Clinical Biochemistry: 61%). The 171 specialists included in the study had 9,823 papers in Medline and 10,140 papers in the Web of Science. The number of Medline papers per specialist was 71 for Clinical Biochemistry...

  19. Activating clinical trials: a process improvement approach.

    Science.gov (United States)

    Martinez, Diego A; Tsalatsanis, Athanasios; Yalcin, Ali; Zayas-Castro, José L; Djulbegovic, Benjamin

    2016-02-24

    The administrative process associated with clinical trial activation has been criticized as costly, complex, and time-consuming. Prior research has concentrated on identifying administrative barriers and proposing various solutions to reduce activation time, and consequently associated costs. Here, we expand on previous research by incorporating social network analysis and discrete-event simulation to support process improvement decision-making. We searched for all operational data associated with the administrative process of activating industry-sponsored clinical trials at the Office of Clinical Research of the University of South Florida in Tampa, Florida. We limited the search to those trials initiated and activated between July 2011 and June 2012. We described the process using value stream mapping, studied the interactions of the various process participants using social network analysis, and modeled potential process modifications using discrete-event simulation. The administrative process comprised 5 sub-processes, 30 activities, 11 decision points, 5 loops, and 8 participants. The mean activation time was 76.6 days. Rate-limiting sub-processes were those of contract and budget development. Key participants during contract and budget development were the Office of Clinical Research, sponsors, and the principal investigator. Simulation results indicate that slight increments on the number of trials, arriving to the Office of Clinical Research, would increase activation time by 11 %. Also, incrementing the efficiency of contract and budget development would reduce the activation time by 28 %. Finally, better synchronization between contract and budget development would reduce time spent on batching documentation; however, no improvements would be attained in total activation time. The presented process improvement analytic framework not only identifies administrative barriers, but also helps to devise and evaluate potential improvement scenarios. The strength

  20. Modulation of the activity of N-methyl-D-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13

    Directory of Open Access Journals (Sweden)

    Vasilescu AN

    2017-03-01

    Full Text Available Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD. Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13, a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment

  1. Clinical markers of vitiligo activity.

    Science.gov (United States)

    Benzekri, Laila; Gauthier, Yvon

    2017-05-01

    Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8 + T lymphocytes, and E-cadherin. The active lesions were associated with hypomelanotic appearance with poorly defined borders (P vitiligo lesion. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Laboratory and clinical evaluation of the radiation-potentiating activity of ethyl-N-bis (2,2-dimethylethylamidinophosphoro) carbamate (AB-132)

    International Nuclear Information System (INIS)

    Regelson, W.; Hananian, J.; Bozzini, M.; Ambrus, C.M.; Bardos, T.J.; Ambrus, J.L.

    1975-01-01

    Ethyl-N-bis (2,2(dimethylethylamidinophosphoro) carbamate (AB-132) has been shown to potentiate the effect of whole-body radiation on inhibition of splenomegaly induced by Friend leukemia virus in ICR/H Swiss mice. The combined effect of AB-132 and radiation does not appear to be related to Friend virus inhibition but seems to act on the proliferating tumor in the spleen. Nine children with advanced cancer were treated with combined adminstration of local radiation and systemic AB-132. Although regression of tumor was seen, no dramatic effect on survival was apparent. One case of metastatic Ewing's sarcoma showed systemic tumor response to AB-132 in addition to localized response to radiation. Bone marrow depression appeared to be the main side effect of combination therapy

  3. Clinical and therapeutic potential of Aconitum heterophyllum

    Directory of Open Access Journals (Sweden)

    Sadia Khurshid

    2015-12-01

    Full Text Available Aconitum heterophyllum is a plant that has very important medicinal value. Lots of phytochemical constituents (metabolites are extracted from this plant, especially diterpene alkaloids which are the main compounds having pharmacological activities such as analgesic and anti-inflammatory. Study of the structures of these compounds was done by the technique of nuclear magnetic resonance.

  4. Fomivirsen: clinical pharmacology and potential drug interactions.

    Science.gov (United States)

    Geary, Richard S; Henry, Scott P; Grillone, Lisa R

    2002-01-01

    Fomivirsen sodium is a 21-base phosphorothioate oligodeoxynucleotide complementary to the messenger RNA of the major immediate-early region proteins of human cytomegalovirus, and is a potent and selective antiviral agent for cytomegalovirus retinitis. Following intravitreal administration, fomivirsen is slowly cleared from vitreous with a half-life of approximately 55 hours in humans. Preclinical studies show that fomivirsen distributes to retina and is slowly metabolised by exonuclease digestion. Clearance from retina was shown to be similarly slow following loading from the vitreous. The estimated half-life for clearance of fomivirsen from retina was 78 hours in monkeys following a 115-microg dose. Because of the low doses coupled with slow disposition from the eye, measurable concentrations of drug are not detected in the systemic circulation following intravitreal administration. Systemically administered phosphorothioate oligodeoxynucleotides are highly bound to albumin and alpha2-macroglobulin in blood plasma. Because fomivirsen does not compete for oxidative metabolic processes involved in clearance of many xenobiotics, the most likely mechanism for drug interactions may be altered protein binding of a coadministered drug. The extremely low systemic exposure to this oligodeoxynucleotide following intravitreal administration largely negates its potential ability to interact with systemically administered drugs. Even if fomivirsen were able to access the blood, protein binding assays indicate that drugs that are site I and site II binders of albumin (warfarin, ibuprofen, salicylic acid) are not displaced in the presence of phosphorothioate oligodeoxynucleotides of various sequences at concentrations orders of magnitude higher than that seen for fomivirsen. Administration of fomivirsen with numerous systemically administered antiretrovirals (for example zidovudine and zalcitabine) as well as systemically administered anticytomegalovirus agents such as foscarnet

  5. In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?

    OpenAIRE

    Golparian, Daniel; Fernandes, Prabhavathi; Ohnishi, Makoto; Jensen, Jörgen S.; Unemo, Magnus

    2012-01-01

    Gonorrhea may become untreatable, and new treatment options are essential. We investigated the in vitro activity of the first fluoroketolide, solithromycin. Clinical Neisseria gonorrhoeae isolates and reference strains (n = 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n = 10) curren...

  6. Antimicrobial activities, toxinogenic potential and sensitivity to ...

    African Journals Online (AJOL)

    Antimicrobial activities, toxinogenic potential and sensitivity to antibiotics of Bacillus strains isolated from Mbuja, an Hibiscus sabdariffa fermented seeds from ... to antibiotics of 26 Bacillus strains (11 Bacillus subtilis, 5 Bacillus megaterium, 4 Bacillus amyloliquefaciens, 4 Bacillus pumilus and 2 Bacillus thuringiensis) ...

  7. Antimicrobial activity of some potential active compounds against ...

    African Journals Online (AJOL)

    Antimicrobial activities of six potential active compounds (acetic acid, chitosan, catechin, gallic acid, lysozyme, and nisin) at the concentration of 500 g/ml against the growth of Escherichia coli, Staphylococcus aureus, Listeria innocua, and Saccharomyces cerevisiae were determined. Lysozyme showed the highest ...

  8. CLINICAL SIGNIFICANCE OF EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAM

    Directory of Open Access Journals (Sweden)

    L. Yu. Glukhova

    2016-01-01

    Full Text Available The article is devoted to some issues of sensitivity and specificity of epileptiform activity in the electroencephalogram (EEG. Epileptiform activity – it is sharp waves and spikes on EEG. Normal EEG does not exclude the diagnosis of epilepsy and viсe versa: presence of epileptiform activity on EEG is not necessarily caused by epilepsy. Several EEGs may be needed to detect epileptiform activity in patients with epilepsy. EEG recording during sleep with the use of different activation methods (hyperventilation, rhythmic photic stimulation, sleep deprivation can increase the probability of epileptiform activity detection. Clinical presentation should be taken into account while interpreting EEG results with registered epileptiform activity. The issues of epileptiform activity classification and differential interpretation of other electrical activity types are also discussed in the article. Main epileptiform patterns, their neurophysiological basis and correlation with clinical manifestations are described.

  9. Ultrasound and ski resort clinics: mapping out the potential benefits.

    Science.gov (United States)

    Evans, C Scott; Harris, N Stuart

    2012-09-01

    Skiing and snowboarding are popular activities that involve high kinetic energies, often at altitude, and injuries are common. As a portable imaging modality, ultrasound may be a useful adjunct for mountainside clinics. This review briefly discusses skier and snowboarder injury profiles and focuses on the role of ultrasound for each injury type. Twenty-two sources including 17 reviews and observational studies were obtained describing skier and snowboarder injuries. Forty-nine studies were identified defining ultrasound applications for these injuries, including 38 reviews and observational studies, 6 case reports or case series, 3 cross-sectional studies, and 2 randomized, blinded studies. Approximately 200 000 rider injuries are evaluated in the Unites States seasonally. Musculoskeletal injuries are the most common, and head, face, neck, and abdominal injuries are also prevalent, as are exacerbations of preexisting disease. Ultrasound has been shown to be useful and accurate for evaluating the aforementioned injury types, including joint, ligament, tendon, and fracture evaluation. Ultrasound has not been extensively studied in the prehospital setting, and only limited data address the utility of how it might influence management in a mountainside clinic setting. Ultrasound has the potential to be a useful diagnostic modality in ski resort clinics. The most promising areas for future, applied studies include evaluation of musculoskeletal injuries (especially injuries to joints and tendons and ruling out fractures), assessing for elevated intracranial pressure in minor head injuries and symptoms of altitude illness, and focused assessment with sonography for trauma and extended focused assessment with sonography for trauma examinations for cases of chest and abdominal trauma of unknown significance. Copyright © 2012 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  10. Active control of electric potential of spacecraft

    Science.gov (United States)

    Goldstein, R.

    1977-01-01

    Techniques are discussed for controlling the potential of a spacecraft by means of devices which release appropriate charged particles from the spacecraft to the environment. Attention is given to electron emitters, ion emitters, a basic electron emitter arrangement, techniques for sensing electric field or potential, and flight experiments on active potential control. It is recommended to avoid differential charging on spacecraft surfaces because it can severely affect the efficacy of emitters. Discharging the frame of a spacecraft with dielectric surfaces involves the risk of stressing the dielectric material excessively. The spacecraft should, therefore, be provided with grounded conductive surfaces. It is pointed out that particles released by control systems can return to the spacecraft.

  11. The Nephrology Clinical Research Nurse Role: Potential Role Conflicts.

    Science.gov (United States)

    Micklos, Lisa

    2016-01-01

    Clinical research nursing is becoming more visible to nephrology professionals. As more nephrology practices and units are participating in clinical trials, clinical research nursing is gaining interest as a career niche among nephrology nurses. This unique specialty requires that nephrology clinical nurse nurses (CRNs) reconcile the roles of nurse as caregiver and nurse as researcher, which may result in a role conflict. Nephrology nurses should be aware that they may experience this role conflict when transitioning from patient care to a position as a clinical research nurse. These nurses can rely on the American Nurses Association's Code of Ethics for Nurses and the Oncology Nursing Society's Oncology Clinical Trials Nurse Competencies to help reconcile the potential role conflict.

  12. In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?

    Science.gov (United States)

    Golparian, Daniel; Fernandes, Prabhavathi; Ohnishi, Makoto; Jensen, Jörgen S.

    2012-01-01

    Gonorrhea may become untreatable, and new treatment options are essential. We investigated the in vitro activity of the first fluoroketolide, solithromycin. Clinical Neisseria gonorrhoeae isolates and reference strains (n = 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n = 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea. PMID:22354296

  13. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against a large collection of clinical Neisseria gonorrhoeae isolates and international reference strains, including those with high-level antimicrobial resistance: potential treatment option for gonorrhea?

    Science.gov (United States)

    Golparian, Daniel; Fernandes, Prabhavathi; Ohnishi, Makoto; Jensen, Jörgen S; Unemo, Magnus

    2012-05-01

    Gonorrhea may become untreatable, and new treatment options are essential. We investigated the in vitro activity of the first fluoroketolide, solithromycin. Clinical Neisseria gonorrhoeae isolates and reference strains (n = 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n = 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea.

  14. Virtual patient activity patterns for clinical learning.

    Science.gov (United States)

    Ellaway, Rachel; Topps, David; Lee, Sonya; Armson, Heather

    2015-08-01

    Virtual patients are software tools that present learners with patient case situations and tasks. Some virtual patients take the learner through a guided case scenario, whereas others require learners to make diagnostic and therapeutic decisions. Much attention has been paid to the design of virtual patients and their use as standalone activities, but rather less attention has been paid to their use in broader educational activities. This article describes a series of activity patterns that make use of virtual patients. The article describes five patterns of clinical teaching activities that make use of virtual patients: independent study activities; collaborative group activities; blended activities; bridging activities; and reference activities. These patterns were developed inductively from the authors' teaching practices over a number of years. These are not the only activity patterns and designs that can make use of virtual patients but they are ones that have been found to be particularly useful over time and in many different contexts. Although the design of educational artifacts such as virtual patients is important, clinical teachers also need to consider the ways in which they are used. Different kinds of activity can employ different kinds of virtual patients of varying levels of complexity. An activity focus can allow clinical teachers to make more effective and broader use of virtual patients. Virtual patients can be used for more than independent study. Clinical teachers are encouraged to explore the multitude of uses that virtual patients can be put to, and the ways in which activities can be constructed around them. Different kinds of activity can employ different kinds of virtual patients, of varying levels of complexity. © 2015 John Wiley & Sons Ltd.

  15. Clinical Potential of Hyperbaric Pressure-Treated Whey Protein

    Science.gov (United States)

    Piccolomini, André F.; Kubow, Stan; Lands, Larry C.

    2015-01-01

    Whey protein (WP) from cow’s milk is a rich source of essential and branched chain amino acids. Whey protein isolates (WPI) has been demonstrated to support muscle accretion, antioxidant activity, and immune modulation. However, whey is not readily digestible due to its tight conformational structure. Treatment of WPI with hyperbaric pressure results in protein unfolding. This enhances protein digestion, and results in an altered spectrum of released peptides, and greater release of essential and branched chain amino acids. Pressurized whey protein isolates (pWPI), through a series of cell culture, animal models and clinical studies, have been demonstrated to enhance muscle accretion, reduce inflammation, improve immunity, and decrease fatigue. It is also conceivable that pWPI would be more accessible to digestive enzymes, which would allow for a more rapid proteolysis of the proteins and an increased or altered release of small bioactive peptides. The altered profile of peptides released from WP digestion could thus play a role in the modulation of the immune response and tissue glutathione (GSH) concentrations. The research to date presents potentially interesting applications for the development of new functional foods based on hyperbaric treatment of WPI to produce products with more potent nutritional and nutraceutical properties. PMID:27417773

  16. Genetic aspects of pediatric asthma: potential clinical role

    African Journals Online (AJOL)

    EL-HAKIM

    Egypt J Pediatr Allergy Immunol 2008; 6(2): 45-50. 45. Genetic aspects of pediatric asthma: potential clinical role. Sarwat E. Deraz. Professor of Pediatrics, Ain Shams University, Cairo. Introduction. Bronchial asthma is a disease of continuing inflammatory disorder of the airways that causes trouble breathing1. It is a major ...

  17. The therapeutic potential of resveratrol: a review of clinical trials.

    Science.gov (United States)

    Berman, Adi Y; Motechin, Rachel A; Wiesenfeld, Maia Y; Holz, Marina K

    2017-01-01

    Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. We found that for neurological disorders, cardiovascular diseases, and diabetes, the current clinical trials show that resveratrol was well tolerated and beneficially influenced disease biomarkers. However resveratrol had ambiguous and sometimes even detrimental effects in certain types of cancers and in NAFLD. In most of the clinical trials, the major obstacle presented was resveratrol's poor bioavailability. Thus, this work provides useful considerations for the planning and design of future pre-clinical and clinical research on resveratrol.

  18. Clinical governance, clinical audit, and the potential value of a database of equine colic surgery.

    Science.gov (United States)

    Mair, Tim

    2009-08-01

    "Clinical governance" is the term used to describe a systematic approach to maintaining and improving the quality of patient care within a health system. This article introduces the concept of clinical governance as a tool for improving the quality of care. It also discusses the potential value of a large database of colic surgery in implementing some of the components of clinical governance in the field of equine colic surgery.

  19. The potential advantages of digital PCR for clinical virology diagnostics.

    Science.gov (United States)

    Hall Sedlak, Ruth; Jerome, Keith R

    2014-05-01

    Digital PCR (dPCR), a new nucleic acid amplification technology, offers several potential advantages over real-time or quantitative PCR (qPCR), the current workhorse of clinical molecular virology diagnostics. Several studies have demonstrated dPCR assays for human cytomegalovirus or HIV, which give more precise and reproducible results than qPCR assays without sacrificing sensitivity. Here we review the literature comparing dPCR and qPCR performance in viral molecular diagnostic assays and offer perspective on the future of dPCR in clinical virology diagnostics.

  20. Clinical practice guidelines: potential misconceptions of the GRADE approach.

    Science.gov (United States)

    Watine, Joseph; Wils, Julien; Augereau, Christine

    2014-01-01

    To challenge the Grading of Recommendations Assessment, Development and Evaluation (GRADE) group to address the potential misconceptions about their approach to grading the strength of recommendations in clinical practice guidelines. Based on our own expertise of health care professionals trying to think in depth about, and using, guidelines, we have identified four such misconceptions. These potential misconceptions are: (1) evidence in medicine means factual or scientific evidence; (2) opinions are a subcategory of evidence; (3) the most important evidence is related to clinical benefits and harms; (4) being virtuous, and principled, does not particularly help in developing the best possible guidelines. We call on the GRADE leadership to address all the above-mentioned misconceptions. These need explicit answers in their manuscript series. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 7T: Physics, safety, and potential clinical applications.

    Science.gov (United States)

    Kraff, Oliver; Quick, Harald H

    2017-12-01

    With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

  2. Miniaturization and globalization of clinical laboratory activities.

    Science.gov (United States)

    Melo, Murilo R; Clark, Samantha; Barrio, Daniel

    2011-04-01

    Clinical laboratories provide an invaluable service to millions of people around the world in the form of quality diagnostic care. Within the clinical laboratory industry the impetus for change has come from technological development (miniaturization, nanotechnology, and their collective effect on point-of-care testing; POCT) and the increasingly global nature of laboratory services. Potential technological gains in POCT include: the development of bio-sensors, microarrays, genetics and proteomics testing, and enhanced web connectivity. In globalization, prospective opportunities lie in: medical tourism, the migration of healthcare workers, cross-border delivery of testing, and the establishment of accredited laboratories in previously unexplored markets. Accompanying these impressive opportunities are equally imposing challenges. Difficulty transitioning from research to clinical use, poor infrastructure in developing countries, cultural differences and national barriers to global trade are only a few examples. Dealing with the issues presented by globalization and the impact of developing technology on POCT, and on the clinical laboratory services industry in general, will be a daunting task. Despite such concerns, with appropriate countermeasures it will be possible to address the challenges posed. Future laboratory success will be largely dependent on one's ability to adapt in this perpetually shifting landscape.

  3. [Focus on the Immunoscore and its potential clinical implications].

    Science.gov (United States)

    El Sissy, Carine; Marliot, Florence; Haicheur, Nacilla; Kirilovsky, Amos; Scripcariu, Dragos; Lagorce-Pagès, Christine; Galon, Jérôme; Pagès, Franck

    2017-02-01

    The role of the immune response at the tumor site is now recognized as crucial in the clinical course of patients with cancer. The importance of the immune cell type, their functional orientation, their density and location within the tumor's regions (tumor/invasion margin) has recently been shown and were grouped together under the term "immune contexture". A strong infiltration by cytotoxic and memory T cells in a Th1-polarized tumor microenvironment appears to have a major prognosis impact. A test called Immunoscore taking into account these various parameters has been suggested to measure in a simple, reproducible and robust manner the intra- and peritumoral immune response. The prognostic value of Immunoscore has recently been validated in colon cancers by a large international retrospective study under the aegis of the Society for Immunotherapy of Cancer (SITC). The Immunoscore could have several potential clinical applications such as prognostic as well as theranostic. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

    Science.gov (United States)

    Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

    2014-07-01

    The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

  5. Clinical implications from monitoring fetal activity.

    Science.gov (United States)

    Rayburn, W F

    1982-12-15

    The monitoring of fetal motion in high-risk pregnancies has been shown to be worthwhile in predicting fetal distress and impending fetal death. The maternal recording of perceived fetal activity is an inexpensive surveillance technique which is most useful when there is chronic uteroplacental insufficiency or when a stillbirth may be expected. The presence of an active, vigorous fetus is reassuring, but documented fetal inactivity required a reassessment of the underlying antepartum complication and further fetal evaluation with real-time ultrasonography, fetal heart rate testing, and biochemical testing. Fetal distress from such acute changes as abruptio placentae or umbilical cord compression may not be predicted by monitoring fetal motion. Although not used for routine clinical investigation, electromechanical devices such as tocodynamometry have provided much insight into fetal behavioral patterns at many stages of pregnancy and in pregnancies with an antepartum complication.

  6. Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.

    Directory of Open Access Journals (Sweden)

    Francesco Celandroni

    Full Text Available The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.

  7. Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.

    Science.gov (United States)

    Celandroni, Francesco; Salvetti, Sara; Gueye, Sokhna Aissatou; Mazzantini, Diletta; Lupetti, Antonella; Senesi, Sonia; Ghelardi, Emilia

    2016-01-01

    The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.

  8. Potential xanthine oxidase inhibitory activity of endophytic Lasiodiplodia pseudotheobromae.

    Science.gov (United States)

    Kapoor, Neha; Saxena, Sanjai

    2014-07-01

    Xanthine oxidase is considered as a potential target for treatment of hyperuricemia. Hyperuricemia is predisposing factor for gout, chronic heart failure, atherosclerosis, tissue injury, and ischemia. To date, only two inhibitors of xanthine oxidase viz. allopurinol and febuxostat have been clinically approved for used as drugs. In the process of searching for new xanthine oxidase inhibitors, we screened culture filtrates of 42 endophytic fungi using in vitro qualitative and quantitative XO inhibitory assays. The qualitative assay exhibited potential XO inhibition by culture filtrates of four isolates viz. #1048 AMSTITYEL, #2CCSTITD, #6AMLWLS, and #96 CMSTITNEY. The XO inhibitory activity was present only in the chloroform extract of the culture filtrates. Chloroform extract of culture filtrate #1048 AMSTITYEL exhibited the highest inhibition of XO with an IC50 value of 0.61 μg ml(-1) which was better than allopurinol exhibiting an IC50 of 0.937 μg ml(-1) while febuxostat exhibited a much lower IC50 of 0.076 μg ml(-1). Further, molecular phylogenetic tools and morphological studies were used to identify #1048 AMSTITYEL as Lasiodiplodia pseudotheobromae. This is the first report of an endophytic Lasiodiplodia pseudotheobromae from Aegle marmelos exhibiting potential XO Inhibitory activity.

  9. Human reporter genes: potential use in clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org

    2007-10-15

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  10. Human reporter genes: potential use in clinical studies

    International Nuclear Information System (INIS)

    Serganova, Inna; Ponomarev, Vladimir; Blasberg, Ronald

    2007-01-01

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  11. Short-term enzalutamide treatment for the potential remission of active surveillance or intermediate-risk prostate cancer: a case study, review, and the need for a clinical trial

    Directory of Open Access Journals (Sweden)

    Moyad MA

    2014-07-01

    Full Text Available Mark A Moyad,1 Mark C Scholz21Department of Urology, Jenkins/Pokempner Preventive and Complementary Medicine, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA; 2Prostate Oncology Specialists, Marina del Rey, CA, USAAbstract: Active surveillance (AS is a widely recognized and utilized option by which prostate cancer patients with less aggressive tumors on diagnosis defer immediate traditional conventional therapy (surgery, radiation and undergo close monitoring by a physician for any clinical or pathologic changes. The juxtaposition of low- to intermediate-risk elderly patients between effective and conventional treatment with associated risks and monitoring without the opportunity for relief of anxiety and other psychological problems can be significant. Minimal and safe treatment over 6 months with the hope of eliminating the existing disease is of significant interest to prostate cancer patients. Unfortunately, dietary supplements have failed to improve and have sometimes even contributed to disease progression. In addition, the use of multiple medications is not always appropriate or safe. In this case study, we administered low doses of enzalutamide (80 mg/day–120 mg/day in an AS patient during a 6 month period. Results showed a significant reduction in tumor size, as evidenced by magnetic resonance imaging and color Doppler, as well as a an undetectable level of prostate specific antigen during, and immediately following treatment. The use of an oral second-generation androgen-receptor signaling inhibitor was shown to be of benefit to patients unwilling to pursue AS and conventional treatment. Administration of enzalutamide did not reduce testosterone levels, but helped maintain good quality of life, was more cost effective at low doses, and was previously shown to be heart healthy and efficacious during early stages of castration-resistant prostate cancer. Although we do not advocate enzalutamide as a treatment

  12. Antimicrobial activities, toxinogenic potential and sensitivity to ...

    African Journals Online (AJOL)

    SAM

    2014-08-27

    Aug 27, 2014 ... 1Department of Food Engineering and Quality Control, University Institute of Technology, P. O. Box 454 Ngaoundere,. Cameroon ... This study was carried out to screen for antimicrobial activities against common pathogenic and food spoilage ...... Antifungal properties of essential oils and some constituents.

  13. Antioxidant potentialities and Antiradical Activities of Oxalis ...

    African Journals Online (AJOL)

    SARAH

    2017-08-31

    Aug 31, 2017 ... Eaten raw or added to stew to make it taste, juice taken by sick people to ... Food, medicinal Eaten as raw vegetable, its juice used as medicine to treat, wound, stomach upset, flue in infants and spice to make the stew tasty. 12. Ha. NK. Food and ..... biological activities. For example, Cushine and Lamb.

  14. Versatile membrane deformation potential of activated pacsin.

    Directory of Open Access Journals (Sweden)

    Shih Lin Goh

    Full Text Available Endocytosis is a fundamental process in signaling and membrane trafficking. The formation of vesicles at the plasma membrane is mediated by the G protein dynamin that catalyzes the final fission step, the actin cytoskeleton, and proteins that sense or induce membrane curvature. One such protein, the F-BAR domain-containing protein pacsin, contributes to this process and has been shown to induce a spectrum of membrane morphologies, including tubules and tube constrictions in vitro. Full-length pacsin isoform 1 (pacsin-1 has reduced activity compared to its isolated F-BAR domain, implicating an inhibitory role for its C-terminal Src homology 3 (SH3 domain. Here we show that the autoinhibitory, intramolecular interactions in pacsin-1 can be released upon binding to the entire proline-rich domain (PRD of dynamin-1, resulting in potent membrane deformation activity that is distinct from the isolated F-BAR domain. Most strikingly, we observe the generation of small, homogenous vesicles with the activated protein complex under certain experimental conditions. In addition, liposomes prepared with different methods yield distinct membrane deformation morphologies of BAR domain proteins and apparent activation barriers to pacsin-1's activity. Theoretical free energy calculations suggest bimodality of the protein-membrane system as a possible source for the different outcomes, which could account for the coexistence of energetically equivalent membrane structures induced by BAR domain-containing proteins in vitro. Taken together, our results suggest a versatile role for pacsin-1 in sculpting cellular membranes that is likely dependent both on protein structure and membrane properties.

  15. Antioxidant activity potential of gamma irradiated carrageenan

    International Nuclear Information System (INIS)

    Abad, Lucille V.; Relleve, Lorna S.; Racadio, Charles Darwin T.; Aranilla, Charito T.; De la Rosa, Alumanda M.

    2013-01-01

    The antioxidant capacity of irradiated κ-, ι-, λ-carrageenans were investigated using the hydroxyl radical scavenging assay, reducing power assay and DPPH radical scavenging capacity assay. The degree of oxidative inhibition increased with increasing concentration and dose. The type of carrageenan had also an influence on its antioxidant activity which followed the order of lambda< iota< kappa. Increase in oxidative property with radiation dose can be attributed mainly to the depolymerization of the carrageenans with corresponding increase in reducing sugar. The antioxidant properties of these carrageenan oligomers were lower than that of ascorbic acid and galactose sugar. - Highlights: • The antioxidant capacity of gamma irradiated κ-, ι-, λ-carrageenans increased with increasing concentration and dose. • The type of carrageenan had an influence on its antioxidant activity which followed the order of lambda< iota< kappa. • Increase in oxidative property with radiation dose can be attributed mainly to the depolymerization of the carrageenans with corresponding increase in reducing sugar

  16. Lipid modulation of intravascular and cellular sodium handling: mechanistic insights and potential clinical implications.

    Science.gov (United States)

    Amaral, Andre C K B; Sposito, Andrei C

    2006-10-01

    Lipid metabolism can modulate structural and functional characteristics of the vascular system. Recent studies suggested that dyslipidemia may also affect the hemodynamic response to salt intake through the impairment of intravascular volume regulation and cellular sodium handling. Indeed, dyslipidemia may affect sodium homeostasis through several pathways, including defective nitric oxide and eicosanoid production, enhanced renin-angiotensin system activity and increased sympathetic response. Moreover, dyslipidemia directly affects cellular membrane viscosity and modifies membrane ion transport activity. In line with this evidence, attenuation of the above mentioned mechanisms has been demonstrated after lipid-lowering treatment. From the clinical point of view, such interaction between plasma lipids and sodium homeostasis may adversely affect the clinical presentation of diseases such as salt-sensitive hypertension, congestive heart failure, renal diseases with proteinuria or sodium retention. This review considers the interplay between plasma lipids and sodium homeostasis and its potential clinical implication.

  17. Mammography - recent technical developments and their clinical potential

    Energy Technology Data Exchange (ETDEWEB)

    Hemdal, Bengt; Mattsson, Soeren [Malmoe Univ. Hospital (Sweden). Dept. of Radiation Physics; Andersson, Ingvar [Malmoe Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Thilander Klang, Anne [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Medical Physics and Biomedical Engineering; Bengtsson, Gert; Jarlman, O. [Lund Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Leitz, Wolfram [Swedish Radiation Protection Authority, Stockholm (Sweden); Bjurstam, Nils [Univ. of North Norway, Troms (Norway). Dept. of Radiology

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  18. Mammography - recent technical developments and their clinical potential

    International Nuclear Information System (INIS)

    Hemdal, Bengt; Mattsson, Soeren; Bjurstam, Nils

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  19. The Methodical Approaches to Activation of Innovative Potential of Enterprise

    Directory of Open Access Journals (Sweden)

    Berveno Oksana V.

    2017-12-01

    Full Text Available The article is aimed at developing theoretical provisions and practical recommendations on methods of management and activation of innovative potential of enterprises. Assessment of innovative potential of enterprise should be carried out from different positions, taking into consideration all external and internal possibilities of enterprise as to carrying out an innovation activity. The system of management of innovation activity and implementation of innovative potential at enterprise should be closely woven in the general management of the enterprise. Activation of innovative potential of enterprise foresees adoption of the whole system of strategic decisions, which are aimed at creation of the most favorable conditions for implementation of innovative potential with obtaining of planned results. The system of activization of innovative potential should develop a number of organizational decisions on interaction of elements of the most innovative potential in the process of innovation activity and cooperation of innovative potential with other subsystems of the enterprise. Results of these organizational decisions in many respects determine efficiency of innovation activity of the enterprise.

  20. Paradigms, promises, and the potential of clinical psychology.

    Science.gov (United States)

    Strauman, T J

    2001-09-01

    Both Plaud's and Ilardi and Feldman's articles call for clinical psychology to redefine itself according to a particular paradigm or "unifying framework." This commentary focuses on the nature of clinical psychology as an applied discipline, whether clinical psychology in fact has an urgent need for a unifying framework, and whether radical behaviorism or cognitive neuroscience could provide such a framework. It is concluded that, as an applied field that draws both theory and method from a number of natural and social sciences, clinical psychology is served best by continued development and appropriation of competing scientific viewpoints rather than by fealty to a single perspective or paradigm. Copyright 2001 John Wiley & Sons, Inc.

  1. ORIGINAL ARTICLES Pharmacologically active: clinical trials and ...

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... There is no reliable published value of pharmaceutical industry expenditure on clinical trials. The Pharmaceutical. Manufacturers Association, on the basis of a survey of its ... To determine the scale of current pharmaceutical R&D and clinical .... African market, a relatively drug-naïve population, and a high.

  2. Clinical potential of implantable wireless sensors for orthopedic treatments.

    Science.gov (United States)

    Karipott, Salil Sidharthan; Nelson, Bradley D; Guldberg, Robert E; Ong, Keat Ghee

    2018-03-21

    Implantable wireless sensors have been used for real-time monitoring of chemicals and physical conditions of bones, tendons and muscles to diagnose and study orthopedic diseases and injuries. Due to the importance of these sensors in orthopedic care, a critical review, which not only analyzes the underlying technologies but also their clinical implementations and challenges, will provide a landscape view on their current state and their future clinical role. Areas covered: By conducting an extensive literature search and following the leaders of orthopedic implantable wireless sensors, this review covers the battery-powered and battery-free wireless implantable sensor technologies, and describes their implementation for hips, knees, spine, and shoulder stress/strain monitoring. Their advantages, limitations, and clinical challenges are also described. Expert commentary: Currently, implantable wireless sensors are mostly limited for scientific investigations and demonstrative experiments. Although rapid advancement in sensors and wireless technologies will push the reliability and practicality of these sensors for clinical realization, regulatory constraints and financial viability in medical device industry may curtail their continuous adoption for clinical orthopedic applications. In the next five years, these sensors are expected to gain increased interest from researchers, but wide clinical adoption is still unlikely.

  3. Potential Anticonvulsant Activity of Ethanol Extracts of Cichorium ...

    African Journals Online (AJOL)

    Potential Anticonvulsant Activity of Ethanol Extracts of Cichorium intybus and Taraxacum serotinum in Rats. Rehab F Abdel-Rahman, Gamal A Soliman, Hasan S Yusufoglu, Irem Tatli-Cankaya, Saleh I Alqasoumi, Serap Arabci Anul, Galip Akaydin ...

  4. The potential role of prehospital administration of activated charcoal

    Science.gov (United States)

    Thakore, S; Murphy, N

    2002-01-01

    Method: Ambulance report forms and case notes were reviewed in all patients presenting to A&E by ambulance after self poisoning. Information was gathered using a standardised abstraction form. The times collected were: time of ingestion, time of call to ambulance control, time picked up, time of arrival in A&E and time seen by doctor. Results: 201 patient records were reviewed. Twenty six were excluded because of incomplete data on report forms or case notes. The median time between ingestion and pick up by an ambulance crew was 77 minutes. This compares with a median of 140 minutes for the time to assessment by medical staff. Seventy three patients were picked up by an ambulance within one hour of overdose, only 11 (15%) of these were seen by medical staff within an hour of ingestion. Forty nine of these 73 patients would have been suitable candidates to receive activated charcoal. Conclusions: The prehospital administration of charcoal provides an opportunity to comply with international guidelines on reducing the absorption of a potentially fatal overdose. The administration of charcoal results in few side effects provided the patient can adequately protect their airway and ambulance staff could be trained in its use. Further studies would be necessary to investigate if this would effect clinical outcome. PMID:11777882

  5. The potential conflict between clinical and judicial decision making heuristics.

    Science.gov (United States)

    Rassin, E; Merckelbach, H

    1999-01-01

    The Gudjonsson Suggestibility Scale (GSS; Gudjonsson, 1984) was introduced as a tool for identifying suspects who are at risk of making false confessions. High GSS-scores indicate a greater risk of making false confessions. Recently, some authors have claimed that low GSS-scores can be used to support the credibility of recovered memories. This new application broadens the use of the GSS in two ways. First, low GSS-scores are considered to possess diagnostic value. Second, the GSS is advocated as a practical tool in clinical settings. This article critically evaluates such a clinical application of the GSS. Our main argument has to do with the incompatibility of basic clinical and judicial decision making heuristics. Psychotherapists, and other medical professionals, should base their decisions on different parameters than judicial professionals. Compared to judicial heuristics, clinical heuristics can be characterized as more empathetic, less critical, and less conservative. Given these differences, clinical conclusions (including those about the accuracy of recovered memories) cannot be easily translated into judicial decisions. If they do enter the judicial domain, these conclusions may lead to dubious forensic decisions. Copyright 1999 John Wiley & Sons, Ltd.

  6. The Smart Drug Delivery System and Its Clinical Potential

    Science.gov (United States)

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  7. The potential role for a pharmacist in a multidisciplinary general practitioner super clinic.

    Science.gov (United States)

    Bajorek, Beata; LeMay, Kate; Gunn, Kate; Armour, Carol

    2015-01-01

    The Australian government's General Practitioner (GP) super clinics programme aims to provide well-integrated, multidisciplinary, patient-centred care for people with chronic disease. However, there is no research into the current role of pharmacists in this setting. To explore the perspectives of GP super clinic staff on current and potential (future) pharmacist-led services provided in this setting. Individual interviews (facilitated using a semi-structured interview guide and thematically analysed) were conducted with purposively sampled staff of a GP super clinic in a semirural location in the state of New South Wales, until theme saturation. Participating staff included (n=9): three GPs, one pharmacist, one nurse, one business manager, and three reception staff. Three themes emerged conveying perspectives on: working relationships between staff; a pharmacist's current role; and potential future roles for a pharmacist. All clinic staff actively engaged the pharmacist in their "team approach". Currently established roles for home medicines reviews (HMRs) and drug information were well supported, but needed to be expanded, for example, with formalised case conferences between GPs, pharmacists, and other staff. New roles needed be explored in auditing medication use, optimising medication records, specialised drug information, dispensing, and prescribing. Although GPs had differing views about opportunities for pharmacists' prescribing in this setting, they saw several benefits to this service, such as reducing the time pressure on GPs to enable more effective consultations. Results suggest a pharmacist's services can potentially be better used within the multidisciplinary super clinic model of care to address current gaps within the semi-rural practice setting. Any future role for the pharmacist could be addressed as part of a formalised, strategic approach to creating an integrated healthcare team, with attention to funding and government legislation.

  8. Results from active spacecraft potential control on the Geotail spacecraft

    International Nuclear Information System (INIS)

    Schmidt, R.; Arends, H.; Pedersen, A.

    1995-01-01

    A low and actively controlled electrostatic potential on the outer surfaces of a scientific spacecraft is very important for accurate measurements of cold plasma electrons and ions and the DC to low-frequency electric field. The Japanese/NASA Geotail spacecraft carriers as part of its scientific payload a novel ion emitter for active control of the electrostatic potential on the surface of the spacecraft. The aim of the ion emitter is to reduce the positive surface potential which is normally encountered in the outer magnetosphere when the spacecraft is sunlit. Ion emission clamps the surface potential to near the ambient plasma potential. Without emission control, Geotail has encountered plasma conditions in the lobes of the magnetotail which resulted in surface potentials of up to about +70 V. The ion emitter proves to be able to discharge the outer surfaces of the spacecraft and is capable of keeping the surface potential stable at about +2 V. This potential is measured with respect to one of the electric field probes which are current biased and thus kept at a potential slightly above the ambient plasma potential. The instrument uses the liquid metal field ion emission principle to emit indium ions. The ion beam energy is about 6 keV and the typical total emission current amounts to about 15 μA. Neither variations in the ambient plasma conditions nor operation of two electron emitters on Geotail produce significant variations of the controlled surface potential as long as the resulting electron emission currents remain much smaller than the ion emission current. Typical results of the active potential control are shown, demonstrating the surface potential reduction and its stability over time. 25 refs., 5 figs

  9. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  10. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....

  11. Sulfur-containing heterocyclic compounds with potential antidiabetic activity

    Directory of Open Access Journals (Sweden)

    E. A. Savateeva

    2014-12-01

    Full Text Available The essential link in the pathogenesis of diabetes mellitus and its complications is a non-enzymatic glycosylation of proteins. However, modern endocrinology lacks of clinically effective pharmaceuticals for its correction. The screening of 23 derivatives of 1,3,4-thiadiazine the ability to inhibit the reaction of non-enzymatic glycosylation of proteins in vitro was held, and 11 the most active compounds of them were selected, also the relationship «structure – activity» was investigated. An essential part of the pathogenesis of diabetes mellitus and its complications is non-enzymatic glycosylation of proteins. However, modern endocrinology lacks clinically effective medicines for its correction.

  12. Activation of fast-twitch fibers assessed with twitch potentiation.

    Science.gov (United States)

    Sasaki, Kazushige; Tomioka, Yukie; Ishii, Naokata

    2012-08-01

    The augmentation of twitch response following brief muscle activation, called twitch potentiation, has been shown to be much more pronounced in fast-twitch than in slow-twitch fibers. We thus explored the possibility of twitch potentiation as a noninvasive measure of fast-twitch fiber activation, by studying its dependence on the intensity of preceding contraction. Twitch contraction of plantar flexor muscles was evoked with supramaximal stimulation of the posterior tibial nerve, before and immediately after 6-s voluntary contractions at intensities of 10-100% of maximal voluntary contraction (MVC). Except for low-intensity contractions (twitch potentiation, the magnitude of which increased with increasing contraction intensity (P twitch potentiation reflects the activation of fast-twitch fibers during a brief contraction. Copyright © 2012 Wiley Periodicals, Inc.

  13. Mutuality: clinical and metapsychological potentials of a failed experiment.

    Science.gov (United States)

    Castillo Mendoza, Carlos Alberto

    2012-03-01

    Ferenczi's experiments with mutual analysis are often dismissed, without acknowledging the results obtained from them and his own cautionary remarks about their limits. Though ultimately failed, Ferenczi's experiments with mutual analysis were a source of clinical and metapsychological knowledge, despite the fact that he was unable to elaborate them in his lifetime. In this paper I connect mutuality to the development of the psyche, especially to the constitutive core of the intrapsychic. To understand the latter, it is necessary to take into account, among others, issues such as the common attribute, the mutual flux between the unconsciouses, the dialogue of unconsciouses, the maternal profundity, the primal relationship with the mother, and, above all, the primal unity between mother and child, which are fundamental for the emergence and development of the primary psychic forces. Incidences of rupture, distortion of the core of mutuality in the psychic life, its loss and disadjustment, by means of external traumatizing forces, and some clinical implications are described.

  14. Improving management of student clinical placements: insights from activity theory.

    Science.gov (United States)

    O'Keefe, Maree; Wade, Victoria; McAllister, Sue; Stupans, Ieva; Burgess, Teresa

    2016-08-24

    An approach to improve management of student clinical placements, the Building Teams for Quality Learning project, was trialed in three different health services. In a previous paper the authors explored in some detail the factors associated with considerable success of this approach at one of these services. In this paper, the authors extend this work with further analysis to determine if the more limited outcomes observed with participants at the other two services could be explained by application of activity theory and in particular the expansive learning cycle. Staff at three health services participated in the Building Teams for Quality Learning project: a dental clinic, a community aged care facility and a rural hospital. At each site a team of seven multi-disciplinary staff completed the project over 9 to 12 months (total 21 participants). Evaluation data were collected through interviews, focus groups and direct observation of staff and students. Following initial thematic analysis, further analysis was conducted to compare the processes and outcomes at each participating health service drawing on activity theory and the expansive learning cycle. Fifty-one interview transcripts, 33 h of workplace observation and 31 sets of workshop field notes (from 36 h of workshops) were generated. All participants were individually supportive of, and committed to, high quality student learning experiences. As was observed with staff at the dental clinic, a number of potentially effective strategies were discussed at the aged care facility and the rural hospital workshops. However, participants in these two health services could not develop a successful implementation plan. The expansive learning cycle element of modeling and testing new solutions was not achieved and participants were unable, collectively to reassess and reinterpret the object of their activities. The application of activity theory and the expansive learning cycle assisted a deeper understanding of

  15. Antimicrobial potentials of silver colloidal (nanorods) on clinical ...

    African Journals Online (AJOL)

    Antimicrobial resistance in developing countries has long been an issue of major concern. Nanotechnology has become an eye opener for the intervention on multiple drug resistance organisms. In this study we investigated the antimicrobial potentials of Silver Nitrate (nanorods) solution used in managing infectious ...

  16. Clinical Activity in General Practice and Cancer

    DEFF Research Database (Denmark)

    Hjertholm, Peter

    2015-01-01

    BACKGROUND AND AIMS Cancer is a common, serious disease and early diagnosis is a cornerstone in the effort to improve the outcome from cancer disease. The general practitioner (GP) plays a crucial role in achieving this goal. Little is known about GPs’ suspicion of cancer and the activities the GPs...... institute in relation to such suspicion. Knowledge is also sparse on any effects of different diagnostic activities in general practice. The overall aims of this thesis were therefore: -to describe how often Danish GPs suspected cancer or other serious diseases and how they acted on the suspicion......, and to analyse how a suspicion influenced the demand for health care services and predicted a future diagnosis of serious disease - to investigate whether variation in GPs’ diagnostic activity influences cancer patients’ prognosis in relation to prostate-specific antigen (PSA) testing and prostate cancer...

  17. Active surveillance for clinically localized prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Klotz, Laurence H

    2014-01-01

    Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS stra......Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection...

  18. [Microsurgery in gynecology. 8 years' clinical activity].

    Science.gov (United States)

    Gaspari, A L; Setti, C; Lania, M; Ipri, D; Ortensi, A

    1989-07-01

    A series of 110 patients given surgical treatment for "mechanical infertility of varying origin in 1980-88 is examined". The classification system proposed for the microsurgical procedures available is based both on personal experience and on the classification of the causes of mechanical infertility in women according to aetiopathogenesis. Clinical results are judged in terms of pregnancies achieved and suggest that while adhesiotomy, salpyngostomy, t-t tubal anastomosis and cornual reimplantation are all useful, fimbrioplasty is less likely to give good results, particularly in the long term. Finally the links between gynaecological microsurgery and F.I.V.E.T. and G.I.F.T. are analysed.

  19. Development of a portable blood irradiator for potential clinical uses

    Energy Technology Data Exchange (ETDEWEB)

    Hungate, F.P.

    1988-12-01

    This document provides an account of the development of a fully portable blood irradiator and the evaluation of its safety and efficacy when implanted in goats, sheep, a baboon and dogs. The program was initiated because the control of lymphocyte populations by irradiation is a potential method for improving success in organ or tissue transplantation and for treating a variety of blood diseases. 15 refs., 27 figs., 2 tabs.

  20. Emerging treatments for overactive bladder: clinical potential of botulinum toxins

    Directory of Open Access Journals (Sweden)

    Tincello DG

    2014-05-01

    Full Text Available Douglas G Tincello,1,2 Tina Rashid,2 Vladimir Revicky21Reproductive Sciences Section, Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK; 2Urogynecology Unit, Women's and Children's Clinical Business Unit, University Hospitals of Leicester National Health Service Trust, Leicester, UKAbstract: Overactive bladder (OAB is a symptom syndrome including urgency, frequency, and nocturia – with or without incontinence. It is a common manifestation of detrusor overactivity (DO. DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on

  1. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.

    Science.gov (United States)

    Cao, Jianzhong; Forrest, J Craig; Zhang, Xuming

    2015-02-01

    With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Intermittent Feeding Schedules—Behavioural Consequences and Potential Clinical Significance

    Directory of Open Access Journals (Sweden)

    Michelle Murphy

    2014-03-01

    Full Text Available Food availability and associated sensory cues such as olfaction are known to trigger a range of hormonal and behavioural responses. When food availability is predictable these physiological and behavioural responses can become entrained to set times and occur in anticipation of food rather than being dependent on the food-related cues. Here we summarise the range of physiological and behavioural responses to food when the time of its availability is unpredictable, and consider the potential to manipulate feeding patterns for benefit in metabolic and mental health.

  3. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  4. Breath acetone as a potential marker in clinical practice.

    Science.gov (United States)

    Ruzsányi, Veronika; Péter Kalapos, Miklós

    2017-06-01

    In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

  5. Potential clinical applications of multi-functional milk proteins and peptides in cancer management.

    Science.gov (United States)

    Chen, H Y F; Mollstedt, O; Tsai, Men-Hwei; Kreider, R B

    2014-01-01

    The progression of cancer involves multiple changes that alter intracellular signaling to promote cell proliferation. Subsequent remodeling of the tumor microenvironment enhances metastasis by manipulating the immune system. Research in the past decade has shown that milk proteins and peptides are often multi-functional, exerting activities such as anti-microbial, immunomodulatory, cancer cell apoptosis, anti-metastasis, and antioxidant effects. Several milk-derived biologics, such as HAMLET (human α-lactalbumin made lethal to tumor cells) and the human recombinant form of lactoferrin, already demonstrated promising results in clinical trials. Lactoferricin peptide analogs are in early clinical development as antimicrobial agents and cancer immunotherapies. In addition, milk proteins and peptides are well tolerated and many exhibit oral bioavailability; thus they may complement standard therapies to boost overall success in cancer treatments. Lactoferrin, colostrum, and specific milk-derived peptide fractions are currently being developed as clinical nutrition for cancer prevention and chemotherapy protection. This review highlights the potential applications of milk proteins and peptides as pharmaceutical drug candidates and clinical nutrition in the overall management of cancer.

  6. Potential antibacterial activity of some Saudi Arabia honey

    Directory of Open Access Journals (Sweden)

    Ahmed G. Hegazi

    2017-02-01

    Full Text Available Aim: The aim of this study was to investigate the potential antibacterial activity of some Saudi Arabia honey against selected bacterial strains of medical importance. Materials and Methods: A total of 10 Saudi Arabia honey used to evaluate their antimicrobial activity against some antibiotic-resistant pathogenic bacterial strains. The bacterial strains were Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Results: The antibacterial activity of Saudi honey against five bacterial strains showed different levels of inhibition according to the type of honey. The overall results showed that the potential activity was differing according to the pathogen and honey type. Conclusion: It could be concluded that the Saudi honey inhibit the growth of bacterial strains and that honey can be used as complementary antimicrobial agent against selected pathogenic bacteria.

  7. Potential and clinical utility of stem cells in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Korff Krause

    2010-03-01

    Full Text Available Korff Krause, Carsten Schneider, Kai Jaquet, Karl-Heinz KuckHanseatic Heart Center Hamburg, Department of Cardiology, Asklepios Hospital St. Georg, Hamburg, GermanyAbstract: The recent identification of bone marrow-derived adult stem cells and other types of stem cells that could improve heart function after transplantation have raised high expectations. The basic mechanisms have been studied mostly in murine models. However, these experiments revealed controversial results on transdifferentiation vs transfusion of adult stem cells vs paracrine effects of these cells, which is still being debated. Moreover, the reproducibility of these results in precisely translated large animal models is still less well investigated. Despite these weaknesses results of several clinical trials including several hundreds of patients with ischemic heart disease have been published. However, there are no solid data showing that any of these approaches can regenerate human myocardium. Even the effectiveness of cell therapy in these approaches is doubtful. In future we need in this important field of regenerative medicine: i more experimental data in large animals that are closer to the anatomy and physiology of humans, including data on dose effects, comparison of different cell types and different delivery routes; ii a better understanding of the molecular mechanisms involved in the fate of transplanted cells; iii more intensive research on genuine regenerative medicine, applying genetic regulation and cell engineering.Keywords: stem cells, cardiovascular disease

  8. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  9. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  10. Clinical Activity in General Practice and Cancer

    DEFF Research Database (Denmark)

    Hjertholm, Peter

    2015-01-01

    institute in relation to such suspicion. Knowledge is also sparse on any effects of different diagnostic activities in general practice. The overall aims of this thesis were therefore: -to describe how often Danish GPs suspected cancer or other serious diseases and how they acted on the suspicion...... and lower endoscopies and colorectal cancer METHODS In Study I, survey data from more than 400 GPs and 4000 consultations were combined with registry data on serious disease. Study II and Study III were based only on registry data. RESULTS In Study I, we saw that a suspicion of cancer or another serious...... are randomised to a more liberal access to lower endoscopies. Alongside this, we need to keep on exploring alternative approaches including the use of iFOBT in symptomatic patients. Overall, this thesis indicates that the role of GPs in the diagnosis of cancer should be strengthened through easy access...

  11. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

    Directory of Open Access Journals (Sweden)

    Krzysztof Roszkowski

    2016-11-01

    Full Text Available The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma. Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months had a better prognosis than those with MGMT methylation alone (OS = 18 months. In patients with astrocytoma anaplasticum (n = 7 with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months. In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

  12. Influence of jasmonic acid as potential activator of induced ...

    Indian Academy of Sciences (India)

    MADU

    resistant and susceptible varieties under the influence of JA. Thus, exogenously applied ... [Mandal M K, Pandey D, Purwar S, Singh U S and Kumar A 2006 Influence of jasmonic acid as potential activator of induced resistance against. Karnal bunt in developing ...... expression; Trends Plant Sci. 2 302–307. MS received 7 ...

  13. Antibacterial activity of essential oils: potential applications in food

    NARCIS (Netherlands)

    Burt, S.A.

    2007-01-01

    Due to its antibacterial activity, oregano oil has lately become interesting as a potential 'natural' food preservative. Oregano oil was found to be a fast acting and effective inhibitor of a strain of Escherichia coli O157:H7, the causative agent of a serious gastro-enteritis, and was lethal to

  14. Antimutagenic and potential anticarcinogenic activities of aloe-vera ...

    African Journals Online (AJOL)

    The study was carried out to verify the potential anticarcinogenic and antimutagenic activity of garlic and aloe-vera. The ability of aqueous garlic extract and Aloe-Vera gel to inhibit mutation in tester strain of Escherichia coli WP2 uvrA was determined in this study. (The tester E. coli tryptophan auxotroph strain was obtained ...

  15. Influence of jasmonic acid as potential activator of induced ...

    Indian Academy of Sciences (India)

    MADU

    Influence of jasmonic acid as potential activator of induced resistance against Karnal bunt in developing spikes of wheat. MIHIR K MANDAL, DINESH PANDEY, SHALINI PURWAR, U S SINGH* and ANIL KUMAR. †. Department of Molecular Biology and Genetic Engineering, College of Basic Sciences and Humanities, ...

  16. Structurally modified fatty acids - clinical potential as tracers of metabolism

    International Nuclear Information System (INIS)

    Dudczak, R.; Schmoliner, R.; Angelberger, P.; Knapp, F.F.; Goodman, M.M.

    1985-01-01

    Recently 15-p-iodophenyl-betamethyl-pentadecanoic acid (BMPPA) was proposed for myocardial scintigraphy, as possible probe of metabolic processes other than β-oxidation. In 19 patients myocardial scintigraphy was done after i.v. BMPPA (2 to 4 mCi). Data were collected (LAO 45 0 /14; anterior/5) for 100 minutes in the fasted patients. From heart (H) and liver (L) organ to background (BG) ratios were calculated, and the elimination (E) behavior was analyzed from BG (V. cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl 3 /MeOH extraction of plasma samples (90 min. pi) both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with benzoic acid, BMPPA and triglycerides. In urine (0 to 2h pi: 4.1% dose) hippuric acid was found. It is concluded that BMPPA is a useful agent for myocardial scintigraphy. Its longer retention in the heart compared to unbranched radioiodinated fatty acids may facilitate SPECT studies. Rate of elimination and plasma analysis indicate the metabolic breakdown of BMPPA. Yet, the complexity of the supposed mechanism may impede curve interpretation in terms of specific metabolic pathways. 19 refs., 5 tabs

  17. Cooperative activity and its potential for learning in tertiary education

    Directory of Open Access Journals (Sweden)

    Cirila Peklaj

    2007-01-01

    Full Text Available A learning situation can be structured in different ways, as an individual, competitive, or cooperative activity. Each of these structures can be used for different purposes and can lead to different learning outcomes. This paper focuses on cooperative activity and its potential for learning in tertiary education. After defining cooperative activity (or, in a broader sense, learning in interaction and introducing the CAMS theoretical framework to analyse cooperative activity, the main discussion focuses on the theoretical reasons for the usefulness of group learning and on the research of effects of cooperative learning on cognitive (metacognitive, affective-motivational and social processes in university students. The key elements that should be established for successful cooperation are also discussed. At the end, a new direction in using cooperative activity in learning—computer supported collaborative learning (CSCL, which emerged with rapid technology development in the last two decades—is presented and discussed.

  18. [Evaluation of biological and clinical potential of paleolithic diet].

    Science.gov (United States)

    Kowalski, Lukasz M; Bujko, Jacek

    2012-01-01

    Accumulating evidences suggest that foods that were regularly consumed during the human primates and evolution, in particular during the Paleolithic era (2.6-0.01 x 10(6) years ago), may be optimal for the prevention and treatment of some chronic diseases. It has been postulated that fundamental changes in the diet and other lifestyle conditions that occurred after the Neolithic Revolution, and more recently with the beginning of the Industrial Revolution are too recent taking into account the evolutionary time scale for the human genome to have completely adjust. In contemporary Western populations at least 70% of daily energy intake is provided by foods that were rarely or never consumed by Paleolithic hunter-gatherers, including grains, dairy products as well as refined sugars and highly processed fats. Additionally, compared with Western diets, Paleolithic diets, based on recently published estimates of macronutrient and fatty acid intakes from an East African Paleolithic diet, contained more proteins and long-chain polyunsaturated fatty acids, and less linoleic acid. Observational studies of hunter-gatherers and other non-western populations lend support to the notion that a Paleolithic type diet may reduce the risk of cardiovascular disease, metabolic syndrome, type 2 diabetes, cancer, acne vulgaris and myopia. Moreover, preliminary intervention studies using contemporary diet based on Paleolithic food groups (meat, fish, shellfish, fresh fruits and vegetables, roots, tubers, eggs, and nuts), revealed promising results including favorable changes in risk factors, such as weight, waist circumference, C-reactive protein, glycated haemoglobin (HbAlc), blood pressure, glucose tolerance, insulin secretion, insulin sensitivity and lipid profiles. Low calcium intake, which is often considered as a potential disadvantage of the Paleolithic diet model, should be weighed against the low content of phytates and the low content of sodium chloride, as well as the high

  19. Detection of efflux pump activity among clinical isolates of ...

    African Journals Online (AJOL)

    Detection of efflux pump activity among clinical isolates of. Staphylococcus and Micrococcus ... Philadelphia, USA, 3Department of Medical Laboratory Science, College of Medicine, University of Lagos, Lagos, Nigeria. *For correspondence: Email: ... Eighteen clinical isolates comprising of 14 S. aureus, 2 S. lentus, 1 S.

  20. Spitzer identification of potentially active Near-Earth Asteroids

    Science.gov (United States)

    Mommert, Michael; Trilling, David; Hora, Joseph; Smith, Howard; Chesley, Steve; Emery, Josh; Farnocchia, Davide; Fazio, Giovanni; Harris, Alan; Mueller, Migo

    2017-04-01

    The separation between asteroids and comets has become less clear with the discovery of a small group of asteroids that display comet-like activity. While the activity is attributed to different mechanisms, some objects seem to activate close to the Sun. Near-Earth Asteroids (NEAs) come close to the Earth and the Sun, constituting a natural laboratory for the study of thermally induced activity. Two NEA sub-populations are especially suspected of being potentially active: dormant comets and near-Sun asteroids. We propose 12.4 hrs of Spitzer IRAC observations of 3 near-Sun asteroids and one dormant comet (3552) Don Quixote, about which we have already published. Our goals are (1) to search for activity in Don Quixote, which showed CO/CO2 activity during its previous apparition and (2) to search for activity and measure the diameters and albedos of the near-Sun asteroids. In combination with a funded ground-based observing program, our results will provide significant legacy value to the investigation of activity in near-Earth asteroids.

  1. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance

  2. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

    Science.gov (United States)

    Sellers, Edward M

    2018-02-01

    This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

  3. Research-active clinical nurses: against all odds.

    Science.gov (United States)

    Siedlecki, Sandra L; Albert, Nancy M

    2017-03-01

    To develop a theoretical understanding of factors that impact decisions of clinical nurses to conduct a research study. Only a small percentage of all nurses are research-active and even fewer clinical nurses are research-active. Several researchers have explored barriers to research activity by clinical nurses, but few have examined why, in spite of all odds, some clinical nurses are research-active. As the purpose of this study was to develop a theoretical understanding of the research-active nurse, a grounded theory approach was used. The sample interviewed for this study consisted of registered nurses (n = 26) who worked in a hospital or ambulatory setting, had daily direct patient contact and had participated as principal investigator on at least one completed clinical nursing research study that was not in fulfilment of an educational requirement. The interviews were digitally recorded and analysed by two researchers using the constant comparative method. The findings from this study suggest that the conduct of research by clinical nurses was the direct result of a clinical trigger, characteristics and beliefs of the nurse about research and their role in generating knowledge, and the presence of support conditions, such as a research mentor. Clinical nurses can and do conduct research, in spite of constraints due to a lack of time, money and/or knowledge, if they have access to research mentors and are practising in a research-supportive environment. Nurses at the bedside are in a unique position to identify problems most in need of solutions. Findings from this study provide a foundation upon which to develop and test various programmes that seek to increase the number of clinical nurses who are research-active. © 2016 John Wiley & Sons Ltd.

  4. Potential Moderators of Physical Activity on Brain Health

    Directory of Open Access Journals (Sweden)

    Regina L. Leckie

    2012-01-01

    Full Text Available Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE, brain derived neurotrophic factor (BDNF, and catechol-O-methyltransferase (COMT along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA, as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function.

  5. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability.

    Science.gov (United States)

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep

    2016-06-01

    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  6. Determining the Phagocytic Activity of Clinical Antibody Samples

    Science.gov (United States)

    McAndrew, Elizabeth G.; Dugast, Anne-Sophie; Licht, Anna F.; Eusebio, Justin R.; Alter, Galit; Ackerman, Margaret E.

    2011-01-01

    Antibody-driven phagocytosis is induced via the engagement of Fc receptors on professional phagocytes, and can contribute to both clearance as well as pathology of disease. While the properties of the variable domains of antibodies have long been considered critical to in vivo function, the ability of antibodies to recruit innate immune cells via their Fc domains has become increasingly appreciated as a major factor in their efficacy, both in the setting of recombinant monoclonal antibody therapy, as well as in the course of natural infection or vaccination1-3. Importantly, despite its nomenclature as a constant domain, the antibody Fc domain does not have constant function, and is strongly modulated by IgG subclass (IgG1-4) and glycosylation at Asparagine 2974-6. Thus, this method to study functional differences of antigen-specific antibodies in clinical samples will facilitate correlation of the phagocytic potential of antibodies to disease state, susceptibility to infection, progression, or clinical outcome. Furthermore, this effector function is particularly important in light of the documented ability of antibodies to enhance infection by providing pathogens access into host cells via Fc receptor-driven phagocytosis7. Additionally, there is some evidence that phagocytic uptake of immune complexes can impact the Th1/Th2 polarization of the immune response8. Here, we describe an assay designed to detect differences in antibody-induced phagocytosis, which may be caused by differential IgG subclass, glycan structure at Asn297, as well as the ability to form immune complexes of antigen-specific antibodies in a high-throughput fashion. To this end, 1 μm fluorescent beads are coated with antigen, then incubated with clinical antibody samples, generating fluorescent antigen specific immune complexes. These antibody-opsonized beads are then incubated with a monocytic cell line expressing multiple FcγRs, including both inhibitory and activating. Assay output can

  7. Active tectonics and earthquake potential of the Myanmar region

    OpenAIRE

    Wang, Yu; Sieh, Kerry; Tun, Soe Thura; Lai, Kuang-Yin; Myint, Than

    2014-01-01

    This paper describes geomorphologic evidence for the principal neotectonic features of Myanmar and its immediate surroundings. We combine this evidence with published structural, geodetic, and seismic data to present an overview of the active tectonic architecture of the region and its seismic potential. Three tectonic systems accommodate oblique collision of the Indian plate with Southeast Asia and extrusion of Asian territory around the eastern syntaxis of the Himalayan mountain range. Subd...

  8. Clinical potential of regulatory T cell therapy in liver diseases: An overview and current perspectives

    Directory of Open Access Journals (Sweden)

    Hannah Claire Jeffery

    2016-09-01

    Full Text Available The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes, that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg. The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients.Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment and Good Manufacturing Practice (GMP facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases, chronic rejection and post-transplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases (GVHD and solid organ transplantations. There have not been any new therapies for the autoimmune liver diseases for more than three decades; thus the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior and microenvironment of Treg before applying the cells to the patients.

  9. Antimicrobial potential of Dialium guineense (Wild.) stem bark on some clinical isolates in Nigeria.

    Science.gov (United States)

    Olajubu, Fa; Akpan, I; Ojo, DA; Oluwalana, Sa

    2012-01-01

    The persistent increase in the number of antibiotic-resistant strains of microorganisms has led to the development of more potent but also more expensive antibiotics. In most developing countries of the world these antibiotics are not readily affordable, thus making compliance difficult. This calls for research into alternative sources of antimicrobials. Dialium guineense is a shrub of the family Leguminosae. Its stem bark is used for the treatment of cough, toothache, and bronchitis. Despite the acclaimed efficacy of D guineense, there is no scientific evidence in its support. This work was carried out to assess the antimicrobial activity of D guineense in vitro against some clinical isolates. D guineense stem bark was collected and 50 gm of air-dried and powdered stem bark of the plant was soaked for 72 hours in 1 l of each of the six solvents used in this study. Each mixture was refluxed, agitated at 200 rpm for 1 hour, filtered using Whatman No. 1 filter paper and, finally, freeze dried. The extracts were then tested for antimicrobial activity using the agar diffusion method. The highest percentage yield of 23.2% was obtained with ethanol. Phytochemical screening showed that D guineense contains anthraquinone, alkaloids, flavonoids, tannins, and saponins. The antimicrobial activity of the extracts revealed a broad spectrum of activity, with Salmonella typhi and Staphylococcus aureusa showing the greatest zones of inhibition (18.0 mm). Only Candida albicans among the fungi tested was inhibited by the extract. The greatest zone of inhibition among the fractions was 16.0 mm. D guineense exhibited bactericidal activity at the 7th and 9th hours against Streptococcus pneumoniae and S. aureus 25923 while the 10th hour against S. typhi and C. albicans. The greatest activity was noted against S pneumoniae, where there was reduced viable cell count after 6 hours of exposure. Stem bark extract of D guineense (Wild.) has the potential to be developed into an antimicrobial

  10. Realizing the clinical potential of cancer nanotechnology by minimizing toxicologic and targeted delivery concerns.

    Science.gov (United States)

    Singh, Sanjay; Sharma, Arati; Robertson, Gavin P

    2012-11-15

    Nanotechnology has the potential to make smart drugs that would be capable of targeting cancer but not normal cells and to load combinations of cooperating agents into a single nanosized particle to more effectively treat this disease. However, to realize the full potential of this technology, the negative aspects associated with these nanoparticles need to be overcome. This review discusses concerns in the field limiting realization of the full clinical potential of this technology, which are toxicity and targeted delivery. Strategies to overcome these hurdles are also reviewed, which could lead to attainment of the full clinical potential of this exciting technology. ©2012 AACR.

  11. Realizing the Clinical Potential of Cancer Nanotechnology by Minimizing Toxicological and Targeted Delivery Concerns

    Science.gov (United States)

    Singh, Sanjay; Sharma, Arati; Robertson, Gavin P.

    2013-01-01

    Nanotechnology has the potential to make smart drugs that would be capable of targeting cancer but not normal cells and loading combinations of cooperating agents into a single nano-sized particle to more effectively treat this disease. However, to realize the full potential of this technology the negative aspects associated with these nanoparticles needs to be overcome. This review discusses concerns in the field limiting realization of the full clinical potential of this technology, which are toxicity and targeted delivery. Strategies to overcome these hurdles are also reviewed which could lead to attainment of the full clinical potential of this exciting technology. PMID:23139207

  12. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

    Directory of Open Access Journals (Sweden)

    Douglas W McMillin

    Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

  13. Evaluation of Potential Impacts of Microbial Activity on Drift Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Y. Wang

    2004-11-18

    ''Evaluation of Potential Impacts of Microbial Activity on Drift Chemistry'' focuses on the potential for microbial communities that could be active in repository emplacement drifts to influence the in-drift bulk chemical environment. This report feeds analyses to support the inclusion or exclusion of features, events, and processes (FEPs) in the total system performance assessment (TSPA) for the license application (LA), but this work is not expected to generate direct feeds to the TSPA-LA. The purpose was specified by, and the evaluation was performed and is documented in accordance with, ''Technical Work Plan For: Near-Field Environment and Transport In-Drift Geochemistry Analyses'' (BSC 2004 [DIRS 172402], Section 2.1). This report addresses all of the FEPs assigned by the technical work plan (TWP), including the development of exclusion arguments for FEPs that are not carried forward to the TSPA-LA. Except for an editorial correction noted in Section 6.2, there were no other deviations from the TWP. This report documents the completion of all assigned tasks, as follows (BSC 2004 DIRS 172402, Section 1.2.1): (1) Perform analyses to evaluate the potential for microbial activity in the waste emplacement drift under the constraints of anticipated physical and chemical conditions. (2) Evaluate uncertainties associated with these analyses. (3) Determine whether the potential for microbes warrants a feed to TSPA-LA to account for predicted effects on repository performance. (4) Provide information to address the ''Yucca Mountain Review Plan, Final Report'' (NUREG-1804) (NRC 2003 [DIRS 163274]) and Key Technical Issues and agreements, as appropriate. (5) Develop information for inclusion or exclusion of FEPs.

  14. Evaluation of Potential Impacts of Microbial Activity on Drift Chemistry

    International Nuclear Information System (INIS)

    Y. Wang

    2004-01-01

    ''Evaluation of Potential Impacts of Microbial Activity on Drift Chemistry'' focuses on the potential for microbial communities that could be active in repository emplacement drifts to influence the in-drift bulk chemical environment. This report feeds analyses to support the inclusion or exclusion of features, events, and processes (FEPs) in the total system performance assessment (TSPA) for the license application (LA), but this work is not expected to generate direct feeds to the TSPA-LA. The purpose was specified by, and the evaluation was performed and is documented in accordance with, ''Technical Work Plan For: Near-Field Environment and Transport In-Drift Geochemistry Analyses'' (BSC 2004 [DIRS 172402], Section 2.1). This report addresses all of the FEPs assigned by the technical work plan (TWP), including the development of exclusion arguments for FEPs that are not carried forward to the TSPA-LA. Except for an editorial correction noted in Section 6.2, there were no other deviations from the TWP. This report documents the completion of all assigned tasks, as follows (BSC 2004 DIRS 172402, Section 1.2.1): (1) Perform analyses to evaluate the potential for microbial activity in the waste emplacement drift under the constraints of anticipated physical and chemical conditions. (2) Evaluate uncertainties associated with these analyses. (3) Determine whether the potential for microbes warrants a feed to TSPA-LA to account for predicted effects on repository performance. (4) Provide information to address the ''Yucca Mountain Review Plan, Final Report'' (NUREG-1804) (NRC 2003 [DIRS 163274]) and Key Technical Issues and agreements, as appropriate. (5) Develop information for inclusion or exclusion of FEPs

  15. In vitro activity of ivermectin against Staphylococcus aureus clinical isolates

    Directory of Open Access Journals (Sweden)

    Shoaib Ashraf

    2018-02-01

    Full Text Available Abstract Background Ivermectin is an endectocide against many parasites. Though being a macrocyclic lactone, its activity against bacteria has been less known, possibly due to the fact that micromolar concentrations at tissue levels are required to achieve a therapeutic effect. Among pathogenic bacteria of major medical significance, Staphylococcus aureus cause a number of diseases in a wide variety of hosts including humans and animals. It has been attributed as one of the most pathogenic organisms. The emergence of methicillin resistance has made the treatment of S. aureus even more difficult as it is now resistant to most of the available antibiotics. Thus, search for alternate anti-staphylococcal agents requires immediate attention. Methods Twenty-one clinical isolates of S. aureus were isolated from bovine milk collected from Lahore and Faisalabad Pakistan. Different anthelmintics including levamisole, albendazole and ivermectin were tested against S. aureus to determine their minimum inhibitory concentrations. This was followed-up by growth curve analysis, spot assay and time-kill kinetics. Results The results showed that ivermectin but not levamisole or albendazole exhibited a potent anti-staphylococcal activity at the concentrations of 6.25 and 12.5 μg/ml against two isolates. Interestingly, one of the isolate was sensitive while the other was resistant to methicillin/cefoxitin. Conclusions Our novel findings indicate that ivermectin has an anti-bacterial effect against certain S. aureus isolates. However, to comprehend why ivermectin did not inhibit the growth of all Staphylococci needs further investigation. Nevertheless, we have extended the broad range of known pharmacological effects of ivermectin. As pharmacology and toxicology of ivermectin are well known, its further development as an anti-staphylococcal agent is potentially appealing.

  16. Amanita phalloides, a potentially lethal mushroom : Its clinical presentation and therapeutic options

    NARCIS (Netherlands)

    Serne, EH; Toorians, AWFT; Gietema, JA; Bronsveld, W; Haagsma, EB; Mulder, POM

    Mushroom poisoning with Amanita phalloides, a rare phenonemon in everyday clinical practice in the Netherlands, must be recognized early in view of its potential morbidity and mortality. In this article 2 cases of Amanita intoxication are presented and the pharmacological basis and clinical

  17. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  18. Potential Role of Activating Transcription Factor 5 during Osteogenesis.

    Science.gov (United States)

    Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

    2016-01-01

    Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  19. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Directory of Open Access Journals (Sweden)

    Deepa Gupta

    2015-01-01

    Full Text Available Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

  20. Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition

    Science.gov (United States)

    Caffa, Irene; D'Agostino, Vito; Damonte, Patrizia; Soncini, Debora; Cea, Michele; Monacelli, Fiammetta; Odetti, Patrizio; Ballestrero, Alberto; Provenzani, Alessandro; Longo, Valter D.; Nencioni, Alessio

    2015-01-01

    Tyrosine kinase inhibitors (TKIs) are now the mainstay of treatment in many types of cancer. However, their benefit is frequently short-lived, mandating the search for safe potentiation strategies. Cycles of fasting enhance the activity of chemo-radiotherapy in preclinical cancer models and dietary approaches based on fasting are currently explored in clinical trials. Whether combining fasting with TKIs is going to be potentially beneficial remains unknown. Here we report that starvation conditions increase the ability of commonly administered TKIs, including erlotinib, gefitinib, lapatinib, crizotinib and regorafenib, to block cancer cell growth, to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway and to strengthen E2F-dependent transcription inhibition. In cancer xenografts models, both TKIs and cycles of fasting slowed tumor growth, but, when combined, these interventions were significantly more effective than either type of treatment alone. In conclusion, cycles of fasting or of specifically designed fasting-mimicking diets should be evaluated in clinical studies as a means to potentiate the activity of TKIs in clinical use. PMID:25909220

  1. Aloe arborescens Polysaccharides: In Vitro Immunomodulation and Potential Cytotoxic Activity.

    Science.gov (United States)

    Nazeam, Jilan A; Gad, Haidy A; Esmat, Ahmed; El-Hefnawy, Hala M; Singab, Abdel-Naser B

    2017-05-01

    Different polysaccharides were isolated from the leaves of Aloe arborescens using the gradient power of hydrogen followed by antitumor and immunomodulatory assay. The total polysaccharide content of different fractions, water-soluble polysaccharide (WAP), acid-soluble polysaccharide (ACP), and alkaline-soluble polysaccharide (ALP), was estimated using a phenol-sulfuric acid spectrophotometric method. WAP possessed a higher content of mannose and glucose than either ACP or ALP. In vitro antitumor activity was investigated in three different cancer cell lines, and in vitro immunomodulatory potential was assessed through phagocytosis and lymphocyte transformation assay. The results showed that WAP and ALP exhibited the most significant cytotoxicity against HepG2 human liver cancer cells, with IC 50 values of 26.14 and 21.46 μg/mL, respectively. In contrast, ALP was able to enhance lymphocyte transformation, whereas WAP had the most potent phagocytic activity. Molecular weight, total sugar and uronic acid content, Fourier transform-infrared analysis, and linkage type of bioactive polysaccharides were investigated. These findings revealed that the potential antitumor activity of the natural agents WAP and ALP was through an immunomodulation mechanism, which verifies the use of the plant as adjuvant supplement for cancer patients suffering immunosuppression during chemotherapy.

  2. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  3. Phenylquinoxalinone CFTR activator as potential prosecretory therapy for constipation.

    Science.gov (United States)

    Cil, Onur; Phuan, Puay-Wah; Son, Jung-Ho; Zhu, Jie S; Ku, Colton K; Tabib, Niloufar Akhavan; Teuthorn, Andrew P; Ferrera, Loretta; Zachos, Nicholas C; Lin, Ruxian; Galietta, Luis J V; Donowitz, Mark; Kurth, Mark J; Verkman, Alan S

    2017-04-01

    Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that stimulated intestinal fluid secretion and normalized stool output in a mouse model of opioid-induced constipation. Here, we report phenylquinoxalinone structure-activity analysis, mechanism of action, animal efficacy data in acute and chronic models of constipation, and functional data in ex vivo primary cultured human enterocytes. Structure-activity analysis was done on 175 phenylquinoxalinone analogs, including 15 synthesized compounds. The most potent compound, CFTR act -J027, activated CFTR with EC 50 ∼ 200 nM, with patch-clamp analysis showing a linear CFTR current-voltage relationship with direct CFTR activation. CFTR act -J027 corrected reduced stool output and hydration in a mouse model of acute constipation produced by scopolamine and in a chronically constipated mouse strain (C3H/HeJ). Direct comparison with the approved prosecretory drugs lubiprostone and linaclotide showed substantially greater intestinal fluid secretion with CFTR act -J027, as well as greater efficacy in a constipation model. As evidence to support efficacy in human constipation, CFTR act -J027 increased transepithelial fluid transport in enteroids generated from normal human small intestine. Also, CFTR act -J027 was rapidly metabolized in vitro in human hepatic microsomes, suggesting minimal systemic exposure upon oral administration. These data establish structure-activity and mechanistic data for phenylquinoxalinone CFTR activators, and support their potential efficacy in human constipation. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Reassessing the Potential Activities of Plant CGI-58 Protein.

    Directory of Open Access Journals (Sweden)

    Abdallah Khatib

    Full Text Available Comparative Gene Identification-58 (CGI-58 is a widespread protein found in animals and plants. This protein has been shown to participate in lipolysis in mice and humans by activating Adipose triglyceride lipase (ATGL, the initial enzyme responsible for the triacylglycerol (TAG catabolism cascade. Human mutation of CGI-58 is the cause of Chanarin-Dorfman syndrome, an orphan disease characterized by a systemic accumulation of TAG which engenders tissue disorders. The CGI-58 protein has also been shown to participate in neutral lipid metabolism in plants and, in this case, a mutation again provokes TAG accumulation. Although its roles as an ATGL coactivator and in lipid metabolism are quite clear, the catalytic activity of CGI-58 is still in question. The acyltransferase activities of CGI-58 have been speculated about, reported or even dismissed and experimental evidence that CGI-58 expressed in E. coli possesses an unambiguous catalytic activity is still lacking. To address this problem, we developed a new set of plasmids and site-directed mutants to elucidate the in vivo effects of CGI-58 expression on lipid metabolism in E. coli. By analyzing the lipid composition in selected E. coli strains expressing CGI-58 proteins, and by reinvestigating enzymatic tests with adequate controls, we show here that recombinant plant CGI-58 has none of the proposed activities previously described. Recombinant plant and mouse CGI-58 both lack acyltransferase activity towards either lysophosphatidylglycerol or lysophosphatidic acid to form phosphatidylglycerol or phosphatidic acid and recombinant plant CGI-58 does not catalyze TAG or phospholipid hydrolysis. However, expression of recombinant plant CGI-58, but not mouse CGI-58, led to a decrease in phosphatidylglycerol in all strains of E. coli tested, and a mutation of the putative catalytic residues restored a wild-type phenotype. The potential activities of plant CGI-58 are subsequently discussed.

  5. Antibacterial and antibiotic potentiating activities of tropical marine sponge extracts.

    Science.gov (United States)

    Beesoo, Rima; Bhagooli, Ranjeet; Neergheen-Bhujun, Vidushi S; Li, Wen-Wu; Kagansky, Alexander; Bahorun, Theeshan

    2017-06-01

    Increasing prevalence of antibiotic resistance has led research to focus on discovering new antimicrobial agents derived from the marine biome. Although ample studies have investigated sponges for their bioactive metabolites with promising prospects in drug discovery, the potentiating effects of sponge extracts on antibiotics still remains to be expounded. The present study aimed to investigate the antibacterial capacity of seven tropical sponges collected from Mauritian waters and their modulatory effect in association with three conventional antibiotics namely chloramphenicol, ampicillin and tetracycline. Disc diffusion assay was used to determine the inhibition zone diameter (IZD) of the sponge total crude extracts (CE), hexane (HF), ethyl acetate (EAF) and aqueous (AF) fractions against nine standard bacterial isolates whereas broth microdilution method was used to determine their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and antibiotic potentiating activity of the most active sponge extract. MIC values of the sponge extracts ranged from 0.039 to 1.25mg/mL. Extracts from Neopetrosia exigua rich in beta-sitosterol and cholesterol displayed the widest activity spectrum against the 9 tested bacterial isolates whilst the best antibacterial profile was observed by its EAF particularly against Staphylococcus aureus and Bacillus cereus with MIC and MBC values of 0.039mg/mL and 0.078mg/mL, respectively. The greatest antibiotic potentiating effect was obtained with the EAF of N. exigua (MIC/2) and ampicillin combination against S. aureus. These findings suggest that the antibacterial properties of the tested marine sponge extracts may provide an alternative and complementary strategy to manage bacterial infections. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Intestinal microflora as potential modifiers of sensitizer activity in vivo

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Clarke, C.; Dawson, K.B.; Simpson, W.; Simmons, D.J.C.

    1984-01-01

    Treatment of mice (some bearing Lewis lung tumors), with penicillin (PEN) at 500 mg/l drinking water for one week prior to treatment with misonidazole (MIS), resulted in: the elimination of their anaerobic cecal flora; a decrease in MIS-induced neurotoxicity; an increase in pharmacological exposure to MIS; a decrease in MIS chemopotentiation; a probable increase in MIS radiosensitization; an increase in MIS induced hypothermia. Assuming no chemical interaction between PEN and MIS, these observations indicate that the intestinal microflora can influence the activity of MIS in vivo. The observed reduction in the neurotoxic but not the radiosensitizing potential of MIS following PEN treatment indicates a therapeutic benefit

  7. Antimicrobial Potential of Momordica charantia L. against Multiresistant Standard Species and Clinical Isolates.

    Science.gov (United States)

    Lucena Filho, José Hardman Sátiro de; Lima, Rennaly de Freitas; Medeiros, Ana Claudia Dantas de; Pereira, Jozinete Vieira; Granville-Garcia, Ana Flávia; Costa, Edja Maria Melo de Brito

    2015-11-01

    The aim of the present study was to evaluate the antibacterial and antifungal potential in vitro of Momordica charantia L. against the microorganisms of clinical interest (standard strains and multiresistant isolates) in order to aggregate scientific information in relation to its use as a therapeutic product. M. charantia L. plant material was acquired in municipality of Malta, Paraiba, Brazil. The extract was obtained through maceration, filtration and then concentrated under reduced pressure in a rotary evaporator, resulting in a dough, and was then dried in an oven for 72 hours at 40°C. Antimicrobial action of ethanolic extract of seed M. charantia L. was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) against standard strains of bacteria, isolates multiresistant bacteria and Candida species, by microdilution in broth method. All organisms were sensitive to the extract, being considered strong antimicrobial activity (MIC and MBC/MFC charantia L. showed strong antimicrobial potential, with bactericidal and fungicidal profile, there is the prospect to constitute a new therapeutic strategy for the control of infections, particularly in multiresistant strains. The use of medicinal plants in treatment of infectious processes have an important function nowadays, due to the limitations of the use of synthetic antibiotics available, related specifically to the microbial resistance emergence.

  8. From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

    Science.gov (United States)

    Youssef, F F; Irving, A J

    2012-06-01

    Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the 'holy grail' of endocannabinoid research.

  9. Exploring the efficiency potential for an active magnetic regenerator

    DEFF Research Database (Denmark)

    Eriksen, Dan; Engelbrecht, Kurt; Haffenden Bahl, Christian Robert

    2016-01-01

    A novel rotary state of the art active magnetic regenerator refrigeration prototype was used in an experimental investigation with special focus on efficiency. Based on an applied cooling load, measured shaft power, and pumping power applied to the active magnetic regenerator, a maximum second-la...... and replacing the packed spheres with a theoretical parallel plate regenerator. Furthermore, significant potential efficiency improvements through optimized regenerator geometries are estimated and discussed......., especially for the pressure drop, significant improvements can be made to the machine. However, a large part of the losses may be attributed to regenerator irreversibilities. Considering these unchanged, an estimated upper limit to the second-law efficiency of 30% is given by eliminating parasitic losses...

  10. Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

    Science.gov (United States)

    Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

    2018-01-01

    Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. PMID:29497294

  11. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    Science.gov (United States)

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

  12. Antioxidant activity and potential photoprotective from amazon native flora extracts.

    Science.gov (United States)

    Martins, Francislene J; Caneschi, César A; Vieira, José L F; Barbosa, Wagner; Raposo, Nádia R B

    2016-08-01

    Plant species are sources of active compounds that can fight and/or prevent damage caused by reactive oxygen species, which enables the development of natural products that can help to prevent premature aging caused by exposure to solar radiation. This study assessed the antioxidant and photoprotective activities of six dried extracts of plants from the Brazilian Amazon biome. Plant extracts were prepared in 70% (v/v) ethanol by dynamic maceration for 72h in the dark, and then filtered, concentrated and lyophilized. The extracts were subjected to a phytochemical screening. The antioxidant activity was measured using a 2,2-diphenyl-1-picrylhydrazyl assay and the photoprotection assay was performed using the diffuse transmittance technique. The data obtained from the antioxidant activity assay was evaluated by Student's t-test for independent samples, with the aid of Statistical Package for Social Sciences v.14.0 for Windows software. The flavonoids represent a special metabolites class present in all analyzed extracts. The antioxidant activity (μgmL(-1)) decreased in the following order: Aniba canelilla (1.80±0.16), Brosimum acutifolium (2.84±0.38), Dalbergia monetaria (5.46±0.17) or Caesalpinia pyramidalis (6.45±1.18), Arrabidaea chica (15.35±0.86), and Aspidosperma nitidum (99.14±2.3). Only D. monetaria showed a considerable sun protection factor allowing for labeling (6.0±0.3). The D. monetaria extract was considered the most promising sample because it had optimal antioxidant and photoprotective activities against solar radiation, considering the limit established by regulatory agencies. These extracts with antioxidant potential can be used in photoprotective formulations, providing synergistic photoprotective effect or elevating the adeed value of the product. Additionally, these formulations are attractive to a population who searchs for products made with natural ingredients. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Substrate and electrode potential affect electrotrophic activity of inverted bioanodes.

    Science.gov (United States)

    Hartline, Rosanna M; Call, Douglas F

    2016-08-01

    Electricity-consuming microbial communities can serve as biocathodic catalysts in microbial electrochemical technologies. Initiating their functionality, however, remains a challenge. One promising approach is the polarity inversion of bioanodes. The objective of this study was to examine the impact of bioanode substrate and electrode potentials on inverted electrotrophic activity. Bioanodes derived from domestic wastewater were operated at -0.15V or +0.15V (vs. standard hydrogen electrode) with either acetate or formate as the sole carbon source. After this enrichment phase, cathodic linear sweep voltammetry and polarization revealed that formate-enriched cultures consumed almost 20 times the current (-3.0±0.78mA; -100±26A/m(3)) than those established with acetate (-0.16±0.09mA; -5.2±2.9A/m(3)). The enrichment electrode potential had an appreciable impact for formate, but not acetate, adapted cultures, with the +0.15V enrichment generating twice the cathodic current of the -0.15V enrichment. The total charge consumed during cathodic polarization was comparable to the charge released during subsequent anodic polarization for the formate-adapted cultures, suggesting that these communities accumulated charge or generated reduced products that could be rapidly oxidized. These findings imply that it may be possible to optimize electrotrophic activity through specific bioanodic enrichment procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Interrelationship among physical activity, quality of life, clinical and ...

    African Journals Online (AJOL)

    A number of complexities surround the health and well-being of patients with type 2 diabetes. These difficulties relate to self-care efforts and outcomes, and several other factors play regulatory functions. This study was carried out to investigate the inter-relationship among physical activity, quality of life, and clinical and ...

  15. Active Interventions in Clinical Practice: Contributions of Gestalt Therapy.

    Science.gov (United States)

    Lammert, Marilyn; Dolan, Mary M.

    1983-01-01

    Describes two dimensions of Gestalt therapy that can enhance clinical practice--orientation to the present and active-experimental style--and examines them in relation to some traditional principles of practice. Gestalt theory offers a method of discovery that is a combination of phenomenology and behaviorism. (JAC)

  16. Chitinolytic activity of endophytic Streptomyces and potential for biocontrol.

    Science.gov (United States)

    Quecine, M C; Araujo, W L; Marcon, J; Gai, C S; Azevedo, J L; Pizzirani-Kleiner, A A

    2008-12-01

    Biological sources for the control of plant pathogenic fungi remain an important objective for sustainable agricultural practices. Actinomycetes are used extensively in the pharmaceutical industry and agriculture owing to their great diversity in enzyme production. In the present study, therefore, we evaluated chitinase production by endophytic actinomycetes and the potential of this for control of phytopathogenic fungi. Endophytic Streptomyces were grown on minimum medium supplemented with chitin, and chitinase production was quantified. The strains were screened for any activity towards phytopathogenic fungi and oomycetes by a dual-culture in vitro assay. The correlation between chitinase production and pathogen inhibition was calculated and further confirmed on Colletotrichum sublineolum cell walls by scanning electron microscopy. This paper reports a genetic correlation between chitinase production and the biocontrol potential of endophytic actinomycetes in an antagonistic interaction with different phytopathogens, suggesting that this control could occur inside the host plant. A genetic correlation between chitinase production and pathogen inhibition was demonstrated. Our results provide an enhanced understanding of endophytic Streptomyces and its potential as a biocontrol agent. The implications and applications of these data for biocontrol are discussed.

  17. Innovating information-delivery for potential clinical trials participants. What do patients want from multi-media resources?

    Science.gov (United States)

    Shneerson, Catherine; Windle, Richard; Cox, Karen

    2013-01-01

    To discover whether the provision of clinical trials information via a multi-media platform could better meet the needs, preferences and practices of potential cancer trial participants. A mixed qualitative and quantitative questionnaire was delivered to 72 participants from cancer support groups to elicit views on the provision and design features of multimedia resources in delivering clinical trials information. Perceived lack of information is an expressed barrier to clinical trials participation. Multimedia resources were viewed positively as a way to address this barrier by most potential clinical trials participants; in particular by helping to align information to individual needs, promote active engagement with information, and by allowing more control of the learning experience. Whilst text remained the most valued attribute of any resource, other highly rated attributes included the resource being simple to use, easily accessible, having a clear focus, incorporating examples and visual aids, and being interactive. Provision of support for the learning resource was also rated highly. As in other areas, such as education, multimedia resources may enhance the delivery and acceptance of information regarding clinical trials. Better alignment of information may have a positive impact on recruitment and retention into clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Nematicidal potential and specific enzyme activity enhancement potential of neem (Azadirachta indica A. Juss.) aerial parts.

    Science.gov (United States)

    Nile, Arti Shivraj; Nile, Shivraj Hariram; Keum, Young Soo; Kim, Doo Hwan; Venkidasamy, Baskar; Ramalingam, Sathishkumar

    2018-02-01

    Nematodes are considered as major plant parasites damaging most of the crops, and neem plant exhibits potential nematicidal and insecticidal properties. This study aimed to check nemato-toxic potential of neem (Azadirachta indica) plant using in vitro and in-planta trials against Meloidogyne incognita. The findings suggested that the neem extracts were lethal to second-stage juvenile (J 2 ) and egg hatching with simultaneous enhancement in treated tomato plant growth. The egg numbers of M. incognita found less sensitive to the aqueous and alcoholic extracts than those of J 2 as per LC 50 values. Complete mortality of J 2 s was recorded at 40, 60, and 80% of neem standard extract (SE) dilutions and for undiluted SE of neem. The undiluted SE extract showed 100% inhibition of egg production. The highest reductions in the number of galls/root system, J 2 population, and egg production were observed with 80, 85, and 82% SE as compared control (untreated distilled water). The maximum 250% growth increment was observed in the length of tomato roots supplemented with neem extracts. Resistance-related enzyme [phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POX)] activities in tomato plant have been increased significantly by supplementation with neem extracts. It appears that the aerial parts of neem (A. indica) extracts showed significant and sustainable eco-friendly nemato-toxic potential towards M. incognita growth inhibition and eradication using alcoholic extracts compared to aqueous. From this study, it was concluded that the neem aerial parts were useful for the control of M. incognita and could be a possible replacement for synthetic nematicides in crop protection with utilization in enhancement of specific enzyme activity in tomato plants.

  19. The potential significance of microbial activity in radioactive waste disposal

    International Nuclear Information System (INIS)

    McCabe, A.M.

    1987-12-01

    The aim of this report is to assess the potential significance of microbial activity in radioactive waste disposal. It outlines the major factors which need to be considered in order to evaluate the importance of microbiological action. These include water and nutritional sources (particularly carbon) hostile conditions (particularly the effects of radiation and pH), the establishment of pH micro-environments and the degradative effect of microbial metabolic by-products on the disposed waste forms. Before an active microbial population can develop there are certain basic requirements for life. These are outlined and the possibility of colonisation occurring within the chemical, radiological and nutritional constraints of a repository are considered. Once colonisation is assumed, the effect of microbial activity is discussed under five headings, i.e. (i) direct attack, (ii) physical disruption (which includes consideration of fissuring processes and void formation), (iii) gas generation (which may be of particular importance), (iv) radionuclide uptake and finally (v) alteration of groundwater chemistry. Particular attention is paid to the possibility of environments becoming established both within the waste form itself (allowing microbes to attack from the inside of the repository outward) or attack on the encapsulant materials (microbes attacking from the outside inward). (author)

  20. MRTF potentiates TEAD-YAP transcriptional activity causing metastasis.

    Science.gov (United States)

    Kim, Tackhoon; Hwang, Daehee; Lee, Dahye; Kim, Jeong-Hwan; Kim, Seon-Young; Lim, Dae-Sik

    2017-02-15

    Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity. We show this interaction of MRTF and YAP is critical for LPA-induced cancer cell invasion in vitro and breast cancer metastasis to the lung in vivo We also demonstrate the significance of MRTF-YAP binding in regulation of YAP activity upon acute actin cytoskeletal damage. Acute actin disruption induces nucleo-cytoplasmic shuttling of MRTF, and this process underlies the LATS-independent regulation of YAP activity. Our results provide clear evidence of crosstalk between MRTF and YAP independent of the LATS kinases that normally act upstream of YAP signaling. Our results also suggest a mechanism by which extracellular stimuli can coordinate physiological events downstream of YAP. © 2016 The Authors.

  1. Decreased antitoxic activities among children with clinical episodes of malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; McKay, V; N'Jie, R

    1998-01-01

    Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor...... necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children...... decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum...

  2. Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies

    NARCIS (Netherlands)

    Coronel, Ruben; de Bakker, Jacques M. T.; Wilms-Schopman, Francien J. G.; Opthof, Tobias; Linnenbank, André C.; Belterman, Charly N.; Janse, Michiel J.

    2006-01-01

    BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues

  3. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Petersen AB

    2013-06-01

    Full Text Available Andreas B Petersen,1 Mikkel Christensen1,21Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark; 2Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, Copenhagen, DenmarkAbstract: The glucagon-like peptide (GLP-1 receptor agonist lixisenatide (Lyxumia® was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of physiological effects generated by GLP-1, which consist of increased insulin secretion, inhibition of glucagon secretion, and decreased gastrointestinal motility alongside the promotion of satiety. In the GetGoal study program, lixisenatide demonstrated significant reductions in glycated hemoglobin (HbA1c, and fasting and postprandial plasma glucose compared with placebo. The effect on glycemia was evident, with both monotherapy and in combination with insulin and various oral antidiabetic agents. Furthermore, a general trend towards reduced bodyweight was reported. In head-to-head trials with the other GLP-1 receptor agonists (exenatide and liraglutide on the market, lixisenatide demonstrated a superior effect with respect to reduction in postprandial plasma glucose and had a tendency towards fewer adverse events. However, lixisenatide seemed to be less efficient or at best, equivalent to exenatide and liraglutide in reducing HbA1c, fasting plasma glucose, and bodyweight. The combination of a substantial effect on postprandial plasma glucose and a labeling with once daily administration separates lixisenatide from the other GLP-1 receptor agonists. The combination of basal insulin, having a lowering effect on fasting plasma glucose, and lixisenatide, curtailing the postprandial glucose excursions, makes sense from a clinical point of view. Not surprisingly, lixisenatide is undergoing clinical development as a combination

  4. Active tectonics and earthquake potential of the Myanmar region

    Science.gov (United States)

    Wang, Yu; Sieh, Kerry; Tun, Soe Thura; Lai, Kuang-Yin; Myint, Than

    2014-04-01

    This paper describes geomorphologic evidence for the principal neotectonic features of Myanmar and its immediate surroundings. We combine this evidence with published structural, geodetic, and seismic data to present an overview of the active tectonic architecture of the region and its seismic potential. Three tectonic systems accommodate oblique collision of the Indian plate with Southeast Asia and extrusion of Asian territory around the eastern syntaxis of the Himalayan mountain range. Subduction and collision associated with the Sunda megathrust beneath and within the Indoburman range and Naga Hills accommodate most of the shortening across the transpressional plate boundary. The Sagaing fault system is the predominant locus of dextral motion associated with the northward translation of India. Left-lateral faults of the northern Shan Plateau, northern Laos, Thailand, and southern China facilitate extrusion of rocks around the eastern syntaxis of the Himalaya. All of these systems have produced major earthquakes within recorded history and continue to present major seismic hazards in the region.

  5. Therapeutic potential of carbohydrates as regulators of macrophage activation.

    Science.gov (United States)

    Lundahl, Mimmi L E; Scanlan, Eoin M; Lavelle, Ed C

    2017-12-15

    It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants. Although there are numerous endogenous and exogenous factors that have an impact on the macrophage polarisation spectrum, this review will focus specifically on prominent macrophage-modulating carbohydrate motifs with a view towards highlighting structure-function relationships and therapeutic potential. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Noise-activated diffusion in the egg-carton potential

    Science.gov (United States)

    Caratti, G.; Ferrando, R.; Spadacini, R.; Tommei, G. E.

    1996-11-01

    The noise-activated diffusion of a classical particle in spatially periodic two-dimensional (2D) systems is studied by solving the corresponding Fokker-Planck equation. The particle is subjected to a periodic deterministic force, to a frictional force, and to a Gaussian white noise. The solution is obtained by extending to 2D the matrix-continued-fraction method for a quite general potential shape. The 2D diffusion coefficient is then numerically calculated for the square egg-carton potential; the analysis is performed over different friction and energy-barrier regimes. Several approximations are compared with the exact numerical results. In particular, the usual 1D diffusion-path approximation is discussed, showing that 2D effects are always present, becoming more and more relevant with decreasing friction. At high friction, a good analytical approximation is shown; on the contrary, none of the available approximations gives satisfactory results in intermediate- and low-damping regimes, which are typical in adatom diffusion on crystal surfaces.

  7. Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Vishakha Grover

    2016-01-01

    Full Text Available Context: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. Aim: To evaluate the correlation of alkaline phosphatase (ALP activity in gingival crevicular fluid (GCF to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Materials and Methods: Study population included 15 smoker male patients in the age group of 35–55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD, relative attachment level (RAL, and GCF ALP activity. Statistical Analysis Used: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. Results: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. Conclusion: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.

  8. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report

    Directory of Open Access Journals (Sweden)

    Hyun Kim

    2016-11-01

    Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

  9. Technology insight: metabonomics in gastroenterology-basic principles and potential clinical applications

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Nielsen, Ole H; Wang, Yulan L

    2008-01-01

    successfully to the study of human diseases, toxicology, microbes, nutrition, and plant biology. This Review introduces the basic principles of nuclear magnetic resonance spectroscopy and commonly used tools for multivariate data analysis, before considering the applications and future potential....... Metabonomics, especially when based on nuclear magnetic resonance spectroscopy, has the potential to identify biomarkers and prognostic factors, enhance clinical diagnosis, and expand hypothesis generation. As a consequence, the use of metabonomics has been extensively explored in the past decade, and applied...... of metabonomics in basic and clinical research, with emphasis on applications in the field of gastroenterology....

  10. Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium

    Directory of Open Access Journals (Sweden)

    Tóth Jaroslav

    2002-02-01

    Full Text Available Abstract Background As part of a study aimed at developing new pharmaceutical products from natural resources, the purpose of this research was twofold: (1 to fractionate crude extracts from the bark of Mahonia aquifolium and (2 to evaluate the strength of the antimutagenic activity of the separate components against one of the common direct-acting chemical mutagens. Methods The antimutagenic potency was evaluated against acridine orange (AO by using Euglena gracilis as an eukaryotic test model, based on the ability of the test compound/fraction to prevent the mutagen-induced damage of chloroplast DNA. Results It was found that the antimutagenicity of the crude Mahonia extract resides in both bis-benzylisoquinoline (BBI and protoberberine alkaloid fractions but only the protoberberine derivatives, jatrorrhizine and berberine, showed significant concentration-dependent inhibitory effect against the AO-induced chloroplast mutagenesis of E. gracilis. Especially berberine elicited, at a very low dose, remarkable suppression of the AO-induced mutagenicity, its antimutagenic potency being almost three orders of magnitude higher when compared to its close analogue, jatrorrhizine. Possible mechanisms of the antimutagenic action are discussed in terms of recent literature data. While the potent antimutagenic activity of the protoberberines most likely results from the inhibition of DNA topoisomerase I, the actual mechanism(s for the BBI alkaloids is hard to be identified. Conclusions Taken together, the results indicate that berberine possesses promising antimutagenic/anticarcinogenic potential that is worth to be investigated further.

  11. Systemic immune activation in HIV and potential therapeutic options.

    Science.gov (United States)

    Sinha, Bhaswati; Rubens, Muni

    2014-04-01

    Advancement in HIV treatment has evolved over the last two decades with the discovery of new drugs and approaches. Studies have demonstrated that HIV-infected individuals have elevated immune activation even during effective antiretroviral therapy. Persistently elevated immune activation has been one of the main obstacles against developing an effective approach for curing HIV. This review examines the mechanism of microbial translocation in HIV-infected individuals and currently investigated potential therapeutic approaches. We searched PubMed and Medline for peer-reviwed articles and recent HIV/AIDS conference abstracts and papers. Narrative review method was used since the objectives of the study were mechanism of microbial translocation and mechanism of action of multiple drugs against it. Microbial translocation occurs as a result of the disruption of epithelial barrier and immunological dysfunction within the intestinal tract due to defective tight junctions, loss of TH17 type CD4(+) T cells, impaired liver architecture, and depletion of intestinal myelomonocytic cells. Potent and effective way to intervene microbial translocation is to target the mechanism of actions involved in microbial translocation by restoration of beneficial microbiata with supplemental probiotics/prebiotics, increased clearance of microbial products from systemic circulation with targeted antibodies and restoration of intestinal integrity with antibiotics. Number of promising drug molecules against microbial translocation are currently under various stages of trials and the results of these trials will hopefully contribute significantly toward effective therapeutic intervention. However, studies also need to explore the effect of combination drugs to abrogate microbial translocation.

  12. POTENTIALS OF IMAGE BASED ACTIVE RANGING TO CAPTURE DYNAMIC SCENES

    Directory of Open Access Journals (Sweden)

    B. Jutzi

    2012-09-01

    Full Text Available Obtaining a 3D description of man-made and natural environments is a basic task in Computer Vision and Remote Sensing. To this end, laser scanning is currently one of the dominating techniques to gather reliable 3D information. The scanning principle inherently needs a certain time interval to acquire the 3D point cloud. On the other hand, new active sensors provide the possibility of capturing range information by images with a single measurement. With this new technique image-based active ranging is possible which allows capturing dynamic scenes, e.g. like walking pedestrians in a yard or moving vehicles. Unfortunately most of these range imaging sensors have strong technical limitations and are not yet sufficient for airborne data acquisition. It can be seen from the recent development of highly specialized (far-range imaging sensors – so called flash-light lasers – that most of the limitations could be alleviated soon, so that future systems will be equipped with improved image size and potentially expanded operating range. The presented work is a first step towards the development of methods capable for application of range images in outdoor environments. To this end, an experimental setup was set up for investigating these proposed possibilities. With the experimental setup a measurement campaign was carried out and first results will be presented within this paper.

  13. Urinary osteoprotegerin: a potential biomarker of lupus nephritis disease activity.

    Science.gov (United States)

    Gupta, R; Aggarwal, A; Sinha, S; Rajasekhar, L; Yadav, A; Gaur, P; Misra, R; Negi, V S

    2016-10-01

    OPG. uOPG is derived from kidneys and helps differentiate active SLE patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN. © The Author(s) 2016.

  14. Polyphasic study of plant- and clinic-associated Pantoea agglomerans strains reveals indistinguishable virulence potential.

    Science.gov (United States)

    Völksch, Beate; Thon, Susanne; Jacobsen, Ilse D; Gube, Matthias

    2009-12-01

    Pantoea species are ubiquitous in nature and occasionally associated with infections caused by contaminated clinical material. Hence, Pantoea agglomerans is considered as an opportunistic pathogen of humans. Since species of the genus Pantoea and closely related species of other Enterobacteriaceae genera are phenotypically very similar, many clinical isolates are misassigned into P. agglomerans based on the use of quick commercial-offered biochemical tests. Our objective was to find markers enabling discrimination between clinical and plant isolates and to assess their virulence potential. We characterized 27 Pantoea strains, including 8 P. agglomerans isolates of clinical, and 11 of plant origin by biochemical tests and genotyping, including analysis of 16S rDNA and gapA gene sequences, and pattern polymorphisms of ITS- and ERIC/REP-DNA. All data showed that no discrete evolution occurred between plant-associated and clinical P. agglomerans isolates. Based on the typing results, five clinical- and five plant-associated P. agglomerans strains representing the majority of clades were tested on a model plant and in embryonated eggs. On soybean plants P. agglomerans strains independent of their origin could develop stable epiphytic populations. Surprisingly, in the embryonated egg model there was no difference of virulence between clinical and vegetable P. agglomerans isolates. However, these strains were significantly less virulent than a phytopathogenic P. ananatis isolate. We suggest that, independent of their origin, all P. agglomerans strains might possess indistinguishable virulence potential.

  15. Pre-clinical studies in cough research: Role of Transient Receptor Potential (TRP) channels

    Science.gov (United States)

    Grace, Megan S.; Dubuis, Eric; Birrell, Mark A.; Belvisi, Maria G.

    2013-01-01

    Cough is a protective reflex and defence mechanism in healthy individuals, which helps clear excessive secretions and foreign material from the lungs. Cough often presents as the first and most persistent symptom of many respiratory diseases and some non-respiratory disorders, but can also be idiopathic, and is a common respiratory complaint for which medical attention is sought. Chronic cough of various aetiologies is a regular presentation to specialist respiratory clinics, and is reported as a troublesome symptom by a significant proportion of the population. Despite this, the treatment options for cough are limited. The lack of effective anti-tussives likely stems from our incomplete understanding of how the tussive reflex is mediated. However, research over the last decade has begun to shed some light on the mechanisms which provoke cough, and may ultimately provide us with better anti-tussive therapies. This review will focus on the in vitro and in vivo models that are currently used to further our understanding of the sensory innervation of the respiratory tract, and how these nerves are involved in controlling the cough response. Central to this are the Transient Receptor Potential (TRP) ion channels, a family of polymodal receptors that can be activated by such diverse stimuli as chemicals, temperature, osmotic stress, and mechanical perturbation. These ion channels are thought to be molecular pain integrators and targets for novel analgesic agents for the treatment of various pain disorders but some are also being developed as anti-tussives. PMID:23474212

  16. Clinical Outcome Following Oral Potentially Malignant Disorder Treatment: A 100 Patient Cohort Study

    Directory of Open Access Journals (Sweden)

    A. Diajil

    2013-01-01

    Full Text Available Oral potentially malignant disorders (PMDs are at risk of transforming to invasive squamous cell carcinoma (SCC, but controversy exists over their management and the precise role of interventional treatment. In this study, a cohort of 100 patients presenting with new, single oral dysplastic PMD lesions were followed for up to 10 years following laser excision. PMDs presented primarily as homogeneous leukoplakias on floor of mouth and ventrolateral tongue sites and showed mainly high-grade dysplasia following analysis of excision specimens. Sixty-two patients were disease-free at the time of the most recent followup, whilst 17 experienced same site PMD recurrence, 14 developed further PMDs at new sites, 5 underwent same site malignant transformation, and 2 developed SCC at new oral sites. Whilst laser excision is an effective therapeutic tool in PMD management, prolonged patient followup and active mucosal surveillance together with clear definitions of clinical outcomes are all essential prerequisites for successful interventional management. Multicentre, prospective, and randomised trials of PMD treatment intervention are urgently required to determine optimal management strategies.

  17. Clinical application of visual evoked potential in orbital cellulitis of infants

    Directory of Open Access Journals (Sweden)

    Xiao-Juan Jing

    2014-07-01

    Full Text Available AIM: To explore the visual evoked potential in infantile orbital cellulitis' clinical applications by monitoring the visual evoked potential changes in infantile orbital cellulitis before, during and after treatment.METHODS: Twenty-three cases of CT diagnosed single orbital cellulitis were examined by the visual evoked potentials. The affected eyes as observation group, and healthy eyes as control group. Comparative observation of visual evoked potential changes in amplitude and incubation period before, during and after the treatment. RESULTS: Compared with the control group, the observation group's visual evoked potential changes included reduced amplitude, extended incubation period. With the treatment progress, the observation group had gradual increase in amplitude, gradual reduction in incubation period. CONCLUSION: In infantile orbital cellulitis, the use of visual evoked potentials is a simple, feasible and effective method to monitoring the visual function during the treatment.

  18. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

    Science.gov (United States)

    Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

    2013-07-01

    Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459

  19. Best Practices for Event-Related Potential Research in Clinical Populations.

    Science.gov (United States)

    Kappenman, Emily S; Luck, Steven J

    2016-03-01

    The event-related potential (ERP) technique has been used for decades to answer important questions about sensory, cognitive, motor, and emotion-related processes in clinical disorders. However, ERP research with clinical populations often involves unique challenges above and beyond the general issues involved in conducting ERP studies in typical research participants. The goal of this paper is to provide an overview of the common challenges that arise in ERP research with clinical populations, including issues in experimental design, recording, analysis, and interpretation of ERPs. In addition, we provide strategies that have proven effective in each of these areas for maximizing the potential of the ERP technique to provide important insights about clinical disorders. The event-related potential (ERP) technique has been used for decades to assess sensory, cognitive, motor, and emotion-related processes in individuals with clinical disorders, and it has great promise for yielding new insights in the future. However, many complex methodological challenges arise in applying this technique to clinical populations, and these challenges must be overcome for the ERP technique to live up to its potential. The goal of this paper is to describe some of the most salient challenges and provide effective strategies for dealing with them. Our own experience has been mainly in schizophrenia, but much of the information presented here applies to any clinical population. We focus our discussion on traditional approaches to ERPs, for which methods been refined over many decades. Information about newer approaches, such as time-frequency analysis, can be found elsewhere (1; 2). We begin with a brief overview of the ERP technique, followed by a discussion of the challenges in designing experiments, practical considerations in recording and analysis, and issues in interpreting ERP effects. The present article is necessarily brief and focused, but broader reviews are available

  20. Engaging clinical nurses in quality and performance improvement activities.

    Science.gov (United States)

    Albanese, Madeline P; Evans, Dietra A; Schantz, Cathy A; Bowen, Margaret; Disbot, Maureen; Moffa, Joseph S; Piesieski, Patricia; Polomano, Rosemary C

    2010-01-01

    Nursing performance measures are an integral part of quality initiatives in acute care; however, organizations face numerous challenges in developing infrastructures to support quality improvement processes and timely dissemination of outcomes data. At the Hospital of the University of Pennsylvania, a Magnet-designated organization, extensive work has been conducted to incorporate nursing-related outcomes in the organization's quality plan and to integrate roles for clinical nurses into the Department of Nursing and organization's core performance-based programs. Content and strategies that promote active involvement of nurses and prepare them to be competent and confident stakeholders in quality initiatives are presented. Engaging clinical nurses in the work of quality and performance improvement is essential to achieving excellence in clinical care. It is important to have structures and processes in place to bring meaningful data to the bedside; however, it is equally important to incorporate outcomes into practice. When nurses are educated about performance and quality measures, are engaged in identifying outcomes and collecting meaningful data, are active participants in disseminating quality reports, and are able to recognize the value of these activities, data become one with practice.

  1. A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors

    International Nuclear Information System (INIS)

    Zhou, Dan; Liu, Yuan; Ye, Josephine; Ying, Weiwen; Ogawa, Luisa Shin; Inoue, Takayo; Tatsuta, Noriaki; Wada, Yumiko; Koya, Keizo; Huang, Qin; Bates, Richard C.; Sonderfan, Andrew J.

    2013-01-01

    In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24 h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6 h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6 h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential. - Highlights: • In human trials some Hsp90 inhibitors cause visual disorders, others do not. • Prolonged inhibition of Hsp90 in the rat eye results in photoreceptor cell death. • Retina/plasma ratio and retinal

  2. Potential ergogenic activity of grape juice in runners.

    Science.gov (United States)

    Toscano, Lydiane Tavares; Tavares, Renata Leite; Toscano, Luciana Tavares; Silva, Cássia Surama Oliveira da; Almeida, Antônio Eduardo Monteiro de; Biasoto, Aline Camarão Telles; Gonçalves, Maria da Conceição Rodrigues; Silva, Alexandre Sérgio

    2015-09-01

    Recent studies have indicated that certain food products have ergogenic potential similar to that of sports supplements. The present study aimed to investigate the potential ergogenic effect of integral purple grape juice on the performance of recreational runners. Twenty-eight volunteers of both sexes (age, 39.8 ± 8.5 years; peak oxygen consumption, 43.2 ± 8.5 mL/(kg·min)) were randomized into either a group that received grape juice (grape juice group (GJG), n = 15; 10 mL/(kg·min) for 28 days) or a group that received an isocaloric, isoglycemic, and isovolumetric control beverage (control group (CG), n = 13). A time-to-exhaustion exercise test, anaerobic threshold test, and aerobic capacity test were performed, together with assessments of markers of oxidative stress, inflammation, immune response, and muscle injury, performed at baseline and 48 h after the supplementation protocol. The GJG showed a significant increase (15.3%) in running time-to-exhaustion (p = 0.002) without significant improvements in either anaerobic threshold (3.6%; p = 0.511) or aerobic capacity (2.2%; p = 0.605). In addition, GJG exhibited significant increases in total antioxidant capacity (38.7%; p = 0.009), vitamin A (11.8%; p = 0.016), and uric acid (28.2%; p = 0.005), whereas α-1-acid glycoprotein significantly decreased (20.2%; p = 0.006) and high-sensitivity C-reactive protein levels remained unchanged. In contrast, no significant changes occurred in any of these variables in the CG. In conclusion, supplementation with purple grape juice shows an ergogenic effect in recreational runners by promoting increased time-to-exhaustion, accompanied by increased antioxidant activity and a possible reduction in inflammatory markers.

  3. Seismic activity parameters of the Finnish potential repository sites

    International Nuclear Information System (INIS)

    Saari, J.

    2000-10-01

    Posiva Oy has started a project for estimating the possible earthquake induced rock movements on the deposition holes containing canisters of spent nuclear fuel. These estimates will be made for the four investigation sites, Romuvaara, Kivetty, Olkiluoto and Haestholmen. This study deals with the current and future seismicity associated with the above mentioned sites. Seismic belts that participate the seismic behaviour of the studied sites have been identified and the magnitude-frequency distributions of these belts have been estimated. The seismic activity parameters of the sites have been deduced from the characteristics of the seismic belts in order to forecast the seismicity during the next 100,000 years. The report discusses the possible earthquakes induced by future glaciation. The seismic interpretation seems to indicate that the previous postglacial faults in Finnish Lapland have been generated in compressional environment. The orientation of the rather uniform compression has been NW-SE, which coincide with the current stress field. It seems that, although the impact of postglacial crustal rebound must have been significant, the impact of plate tectonics has been dominant. A major assumption of this study has been that future seismicity will generally resemble the current seismicity. However, when the postglacial seismicity is concerned, the magnitude-frequency distribution is likely different and the expected maximum magnitude will be higher. Maximum magnitudes of future postglacial earthquakes have been approximated by strain release examinations. Seismicity has been examined within the framework of the lineament maps, in order to associate the future significant earthquakes with active fault zones in the vicinity of the potential repository sites. (orig.)

  4. Lipid nanocarriers containing a levodopa prodrug with potential antiparkinsonian activity.

    Science.gov (United States)

    Ravani, Laura; Sarpietro, Maria Grazia; Esposito, Elisabetta; Di Stefano, Antonio; Sozio, Piera; Calcagno, Mariangela; Drechsler, Markus; Contado, Catia; Longo, Francesco; Giuffrida, Maria Chiara; Castelli, Francesco; Morari, Michele; Cortesi, Rita

    2015-03-01

    This paper describes the production, characterization and in vivo activity of lipid nanocarriers (LN) containing a levodopa prodrug (LD-PD) with therapeutic potential in Parkinson's disease. LD is the mainstay of the pharmacotherapy of Parkinson's disease. However, after a good initial response, motor fluctuations, dyskinesia and loss of efficacy, develop over time, partly due to oscillations in plasma and brain levels of the drug. LD-PD was produced with the aim of prolonging the pharmacological activity of LD. To improve solubility, and simultaneously provide a long lasting release and therapeutic efficacy, the prodrug was formulated in tristearin/lecithin LN. The obtained formulation was homogeneous in particle size and remained stable for up to 2months from preparation. For the three different tested LD concentrations, namely 1.25, 2.5 and 5.0mg/ml, the morphological characterization revealed no substantial differences between unloaded and LD-PD loaded LN. The calorimetric test showed an interaction between the lipid phase and the loaded prodrug. In vitro studies using the dialysis method and enzymatic degradation procedure showed that the LD-PD loaded LN provided a controlled prodrug release. Finally, two behavioural tests specific to akinesia (bar test) or akinesia/bradykinesia (drag test) performed in 6-hydroxydopamine hemilesioned mice (a model of Parkinson's disease) demonstrated that the LD-PD loaded LN attenuated parkinsonian disabilities, showing a slightly reduced maximal efficacy but a longer lasting action (up to 24h) than an equal dose of LD. We conclude that LD-PD loaded LN may represent a future LD formulation useful in Parkinson's disease therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Contribution of plasminogen activation towards the pathogenic potential of oral streptococci.

    Directory of Open Access Journals (Sweden)

    Andreas Itzek

    Full Text Available Oral streptococci are a heterogeneous group of human commensals, with a potential to cause serious infections. Activation of plasminogen has been shown to increase the virulence of typical human pathogenic streptococci such as S. pneumoniae. One important factor for plasminogen activation is the streptococcal α-enolase. Here we report that plasminogen activation is also common in oral streptococci species involved in clinical infection and that it depends on the action of human plasminogen activators. The ability to activate plasminogen did not require full conservation of the internal plasminogen binding sequence motif FYDKERKVY of α-enolase that was previously described as crucial for increased plasminogen binding, activation and virulence. Instead, experiments with recombinant α-enolase variants indicate that the naturally occurring variations do not impair plasminogen binding. In spite of these variations in the internal plasminogen binding motif oral streptococci showed similar activation of plasminogen. We conclude that the pathomechanism of plasminogen activation is conserved in oral streptococci that cause infections in human. This may contribute to their opportunistic pathogenic character that is unfurled in certain niches.

  6. Active learning reduces annotation time for clinical concept extraction.

    Science.gov (United States)

    Kholghi, Mahnoosh; Sitbon, Laurianne; Zuccon, Guido; Nguyen, Anthony

    2017-10-01

    To investigate: (1) the annotation time savings by various active learning query strategies compared to supervised learning and a random sampling baseline, and (2) the benefits of active learning-assisted pre-annotations in accelerating the manual annotation process compared to de novo annotation. There are 73 and 120 discharge summary reports provided by Beth Israel institute in the train and test sets of the concept extraction task in the i2b2/VA 2010 challenge, respectively. The 73 reports were used in user study experiments for manual annotation. First, all sequences within the 73 reports were manually annotated from scratch. Next, active learning models were built to generate pre-annotations for the sequences selected by a query strategy. The annotation/reviewing time per sequence was recorded. The 120 test reports were used to measure the effectiveness of the active learning models. When annotating from scratch, active learning reduced the annotation time up to 35% and 28% compared to a fully supervised approach and a random sampling baseline, respectively. Reviewing active learning-assisted pre-annotations resulted in 20% further reduction of the annotation time when compared to de novo annotation. The number of concepts that require manual annotation is a good indicator of the annotation time for various active learning approaches as demonstrated by high correlation between time rate and concept annotation rate. Active learning has a key role in reducing the time required to manually annotate domain concepts from clinical free text, either when annotating from scratch or reviewing active learning-assisted pre-annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. [Clinical research on repairing alveolar cleft with osteoinduction active material].

    Science.gov (United States)

    She, Xiao-ming; Zhang, Qian; Tian, Kun; Yang, Li; Xiong, Gui-fa

    2010-08-01

    To study the feasibility and authenticity of repairing alveolar defects in alveolar cleft patients with osteoinduction active material (OAM) in clinic. Twenty-seven cases of alveolar defect chosen from clinic were divided into two groups (test group and control group). For test group (12 cases), OAM was transplanted to repair the alveolar cleft. For control group (15 cases), autogenous ilium cancellous bone were transplanted into the defect region to repair alveolar cleft. At 6 months after operation, CT and three-dimensional reconstruction were used to observe alveolar appearance, and the effect and clinical success rate of recover alveolar cleft by using different repair material were compared. In the 27 cases, all the maxillary continuity was restored except two of test group and two of control group. There was no significant difference between test group and control group regarding the clinical success rate of the alveolar cleft repair (P = 1.000). OAM was used to repair the alveolar cleft that can result in new bone formations and the burgeon of canines from the bone grafted areas. There is no significant difference between OAM and autogenous ilium cancellous bone regarding the effect of the alveolar cleft repair.

  8. Screening marine organisms for antimicrobial activity against clinical pathogens

    Digital Repository Service at National Institute of Oceanography (India)

    PrabhaDevi; Wahidullah, S.; Tonima, K.; DeSouza, L.

    extracts of forty marine organisms belonging to different phyla and fractions of active extracts were screened for their antimicrobial effects on human pathogens. A broad panel of microbial pathogens associated with various skin infections, urinary... tract, gastrointestinal infections and waterborne diseases, has been included. The aim of the present study was to identify potential marine sources based on antimicrobial assay. ___________ *Corresponding author Telephone: 91(0)832 2450392 Fax...

  9. Activation of Transient Receptor Potential Vanilloid 4 Increases NMDA-Activated Current in Hippocampal Pyramidal Neurons.

    Science.gov (United States)

    Li, Lin; Qu, Weijun; Zhou, Libin; Lu, Zihong; Jie, Pinghui; Chen, Lei; Chen, Ling

    2013-01-01

    The glutamate excitotoxicity, mediated through N-methyl-d-aspartate receptors (NMDARs), plays an important role in cerebral ischemia injury. Transient receptor potential vanilloid 4 (TRPV4) can be activated by multiple stimuli that may happen during stroke. The present study evaluated the effect of TRPV4 activation on NMDA-activated current (INMDA) and that of blocking TRPV4 on brain injury after focal cerebral ischemia in mice. We herein report that activation of TRPV4 by 4α-PDD and hypotonic stimulation increased INMDA in hippocampal CA1 pyramidal neurons, which was sensitive to TRPV4 antagonist 10 μ M/2 μ 1/mouse [DOSAGE ERROR CORRECTED] and NMDAR antagonist AP-5, indicating that TRPV4 activation potentiates NMDAR response. In addition, the increase in INMDA by hypotonicity was sensitive to the antagonist of NMDAR NR2B subunit, but not of NR2A subunit. Furthermore, antagonists of calcium/calmodulin-dependent protein kinase II (CaMKII) significantly attenuated hypotonicity-induced increase in INMDA, while antagonists of protein kinase C or casein kinase II had no such effect, indicating that phosphorylation of NR2B subunit by CaMKII is responsible for TRPV4-potentiated NMDAR response. Finally, we found that intracerebroventricular injection of 10 μ m/2 μ 1/mouse [DOSAGE ERROR CORRECTED] after 60 min middle cerebral artery occlusion reduced the cerebral infarction with at least a 12 h efficacious time-window. These findings indicate that activation of TRPV4 increases NMDAR function, which may facilitate glutamate excitotoxicity. Closing TRPV4 may exert potent neuroprotection against cerebral ischemia injury through many mechanisms at least including the prevention of NMDAR-mediated glutamate excitotoxicity.

  10. [Antifungal activity of melanin in clinical isolates of Candida spp].

    Science.gov (United States)

    Fuentes, Marisol; Hernández, Romané; Gordillo, Diego; Amaro, José; Falconer, Mary A; Alburquenque, Claudio; Tapia, Cecilia V

    2014-02-01

    Melanocytes are cells located in epidermis and mucous membranes that synthesize melanin and cytokines. It is known that melanin has antimicrobial activity and that melanocytes are melanized in presence of microbial molecules. To study the antifungal activity of melanin on Candida spp. The minimum inhibitory concentration (MIC) to melanin was determined in 4 Candida ATCC strains (C. albicans SC5314, C. parapsilosis 22019, C. glabrata 2001, C. krusei 6258) and 56 clinical isolates of Candida spp. (33 C. albicans, 12 C. glabrata, 3 C. famata, 3 C. krusei, 3 C. parapsilosis, 2 C. tropicalis) using a broth microdilution method. In addition, the antifungal activity of melanocytes and mice melanoma cells was tested against C. albicans. Melanin inhibited the tested isolates, including the susceptible dose-dependent and fluconazole-resistant strains; MIC range and MIC50 were 0.09-50 μg/mL and 6.25 μg/mL, respectively. Pigmented cells lysates inhibited C. albicans. Melanin is able to inhibit clinical isolates of Candida spp. Melanization could be an important protective mechanism of melanocytes.

  11. Clinical pharmacology and therapeutic potential of artemisinin and its derivatives in the treatment of malaria

    NARCIS (Netherlands)

    de Vries, P. J.; Dien, T. K.

    1996-01-01

    Artemisinin and its derivatives are renowned for their potent antimalarial activity. They have found their way into clinical use in many areas where malaria is endemic. The in vitro concentration at which artemisinin can inhibit 50% of the growth of Plasmodium falciparum ranges from 3 to 30

  12. Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail and Robust Older Inpatients.

    Science.gov (United States)

    Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela

    2015-10-01

    A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.

  13. Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

    International Nuclear Information System (INIS)

    Rockwell, S.; Kapp, D.S.

    1982-01-01

    The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses

  14. Study of the potential of using 9B(p,n) for BNCT clinical trials

    International Nuclear Information System (INIS)

    Stone, N.; Bleuel, D.; Donahue, R.; Ludewigt, B.A.; Chu, W.T.

    2000-01-01

    The potential of using a 30-MeV proton accelerator utilizing the 9 Be(p,n) 9 B reaction as a neutron source for BNCT (Boron Neutron Capture Therapy) was investigated. MCNPX (Monte Carlo Neutron Photon-transport code X) was used to calculated neutron spectra and yields for comparison against existing experimental data and for the moderator optimization. Moderator performance was assessed using MCNPX and clinical efficacy was assessed using BNCT-RTPE to estimate in-phantom dose distributions and neutron fluences. The optimized source and moderator gave comparable tumor doses and treatment times to the clinical trials recently completed at the Brookhaven Medical Research Reactor (BMRR). (author)

  15. Investigation of the antifungal potential of linalool against clinical isolates of fluconazole resistant Trichophyton rubrum.

    Science.gov (United States)

    de Oliveira Lima, M I; Araújo de Medeiros, A C; Souza Silva, K V; Cardoso, G N; de Oliveira Lima, E; de Oliveira Pereira, F

    2017-06-01

    The aim of this study was to investigate the activity of the monoterpene linalool against clinical isolates of Trichophyton rubrum. Initially, a sensitivity assay for commercial antifungals with solid disks in diffusion medium was performed. Minimum inhibitory concentration (MIC) of linalool and ketoconazole (positive control) were determined by microdilution in RPMI 1640 medium (CLSI M38-A2). We then evaluated the action of linalool and ketoconazole at different concentrations (1/2MIC, MIC and 2×MIC) on mycelial growth (radial mycelial growth), conidia production and conidia germination using a hemacytometer. The effects on cell membrane (release of intracellular material) were also investigated. Finally, changes in fungal morphology as induced by the test drugs were analyzed. Based on the sensitivity tests, the fungal strains showed resistance to 5-fluorocytosine and fluconazole. The linalool MIC values ranged from 256μg/mL to 512μg/mL, whereas ketoconazole showed values of 4μg/mL to 8μg/mL. For the LM 305 strain, the test drugs showed the following MIC values: linalool 256μg/mL and ketoconazole 8μg/mL. The mycelial growth of T. rubrum LM 305 was inhibited by linalool (2×MIC) and ketoconazole (1/2MIC, MIC, 2×MIC), in 7 days of treatment (PLinalool also caused leakage of intracellular material (Plinalool and ketoconazole to induce micro-morphological changes, forming abnormal, wide, short and crooked hyphae. Based on these results, we conclude that linalool presents as an antifungal agent with anti-Trichophyton rubrum potential, an important dermatophytosis agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function

    Directory of Open Access Journals (Sweden)

    Jovancevic Jelena

    2012-06-01

    Full Text Available Abstract Background Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. Methods/Design This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. Discussion This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span. The study is IRB approved and the number is: PRO08080012 ClinicalTrials.gov Identifier: NCT01443455

  17. A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function.

    Science.gov (United States)

    Jovancevic, Jelena; Rosano, Caterina; Perera, Subashan; Erickson, Kirk I; Studenski, Stephanie

    2012-06-06

    Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span.The study is IRB approved and the number is: PRO08080012ClinicalTrials.gov Identifier: NCT01443455.

  18. Adhesion molecules levels in blood correlate with MRI activity and clinical activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Millers, A.; Enina, G.; Platkajis, A.; Metra, M.; Kukaine, R.

    2002-01-01

    Research into pathogenesis of multiple sclerosis (MS) has prompted efforts to identify immunological markers associated with disease activity. Adhesion molecules ICAM-1 and VCAM-1 are associated with inflammatory mediated blood-brain barrier (BBB) dysfunction. In this study investigates the correlation between blood level of circulating ICAM-1 and VCAM-1 and magnetic resonance imaging (MRI) activity in different clinical phases of patients with MS. We show that RRMS and SPMS patients in clinically active phase with Gd-enhancing lesions in CNS had higher blood levels of cICAM-1 and cVCAM-1 compared these parameters levers of RRMS patients in remission stage. These results suggest that cICAM-1 and cVCAM-1 is a sensitive indicator of disease activity associated with BBB inflammatory dysfunction. Elevated blood level of cICAM-1 more strongly correlated with clinical activity and BBB damage, than cVCAM-1 and that could be used as biological marker of disease activity. Circulating VCAM-1 as an early indicator of BBB disturbance, may also serve as marker of beneficial activity in relapses phase of MS course. (authors)

  19. Physical activity and telomere length: Impact of aging and potential mechanisms of action.

    Science.gov (United States)

    Arsenis, Nicole C; You, Tongjian; Ogawa, Elisa F; Tinsley, Grant M; Zuo, Li

    2017-07-04

    Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes. This relationship is particularly evident in older individuals, suggesting a role of physical activity in combating the typical age-induced decrements in telomere length. To date, a small number of exercise interventions have been executed to examine the potential influence of chronic exercise on telomere length, but these studies have not fully established such relationship. Several potential mechanisms through which physical activity or exercise could affect telomere length are discussed, including changes in telomerase activity, oxidative stress, inflammation, and decreased skeletal muscle satellite cell content. Future research is needed to mechanistically examine the effects of various modalities of exercise on telomere length in middle-aged and older adults, as well as in specific clinical populations.

  20. Pinus massoniana Bark Extract: Structure-Activity Relationship and Biomedical Potentials.

    Science.gov (United States)

    Feng, Jiao; Zhang, Xiao-Lu; Li, Ying-Ya; Cui, Ying-Yu; Chen, Yi-Han

    2016-01-01

    Proanthocyanidins (PAs) belong to the condensed tannin subfamily of natural flavonoids. Recent studies have shown that the main bioactive compounds of Pinus massoniana bark extract (PMBE) are PAs, especially the proanthocyanidins B series, which play important roles in cell cycle arrest, apoptosis induction and migration inhibition of cancer cells in vivo and in vitro. PA-Bs are mixtures of oligomers and polymers composed of flavan-3-ol, and the relationship between their structure and corresponding biomedical potentials is summarized in this paper. The hydroxyl at certain positions or the linkage between different carbon atoms of different rings determines or affects their anti-oxidant and free radical scavenging bioactivities. The degree of polymerization and the water solubility of the reaction system also influence their biomedical potential. Taken together, PMBE has a promising future in clinical drug development as a candidate anticancer drug and as a food additive to prevent tumorigenesis. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of PMBE, its active constituents and their derivatives.

  1. Brief hierarchical assessment of potential treatment components with children in an outpatient clinic.

    OpenAIRE

    Harding, J; Wacker, D P; Cooper, L J; Millard, T; Jensen-Kovalan, P

    1994-01-01

    Seven patients conducted assessments in an outpatient clinic using a prescribed hierarchy of antecedent and consequence treatment components for their children's problem behavior. Brief assessment of potential treatment components was conducted to identify variables that controlled the children's appropriate behavior. Experimental control via a brief reversal was achieved for 6 of the 7 children, (1 child continued to behave appropriately following initial improvement in behavior). For these ...

  2. Clinical Potential of Digital Linear Tomosynthesis Imaging of Total Joint Arthroplasty

    OpenAIRE

    Gomi, Tsutomu; Hirano, Hiroshi

    2007-01-01

    The present study was performed to evaluate the potential for clinical application of digital linear tomosynthesis in imaging hip prostheses. Volumetric x-ray digital linear tomosysnthesis was used to image hip prostheses. The tomosynthesis was compared to metal artifact reduction (MAR) computed tomography (CT), and non-MAR CT scans of a prosthesis case. The effectiveness of this method in enhancing visibility of a prosthesis case was quantified in terms of the signal-to-noise ratio (SNR), an...

  3. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease ...... knowledge of the biology of TIMP-1 as well as the potential use of TIMP-1 as a biological marker in the management of CRC patients....

  4. Clinical Utility and Limitations of Intraoperative Monitoring of Visual Evoked Potentials

    OpenAIRE

    Luo, Yeda; Regli, Luca; Bozinov, Oliver; Sarnthein, Johannes

    2015-01-01

    OBJECTIVES During surgeries that put the visual pathway at risk of injury, continuous monitoring of the visual function is desirable. However, the intraoperative monitoring of the visual evoked potential (VEP) is not yet widely used. We evaluate here the clinical utility of intraoperative VEP monitoring. METHODS We analyzed retrospectively 46 consecutive surgeries in 2011-2013. High luminance stimulating devices delivered flash stimuli on the closed eyelid during intravenous anesthesia. We...

  5. Nrf2 activators as potential modulators of injury in human kidney cells

    Directory of Open Access Journals (Sweden)

    Amandla Atilano-Roque

    2016-01-01

    Full Text Available Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2-like 2 (Nrf2 is a transcription factor involved in kidney protectant effects. The purpose of this study was to determine whether the Nrf2 activators oltipraz, sulforaphane, and oleanolic acid could protect human kidney cells against cisplatin-induced injury and to compare the protective effects between three Nrf2 activators. Human proximal tubule cells (hPTC and human embryonic kidney 293 cells (HEK293 were exposed to cisplatin doses in the absence and presence of Nrf2 activators. Pre- and delayed-cisplatin and Nrf2 activator exposures were also assessed. Cell viability was enhanced with Nrf2 activator exposures, with differences detected between pre- and delayed-treatments. Both sulforaphane and oltipraz increased the expression of anti-oxidant genes GCLC and NQO1. These findings suggest potential human kidney protective benefits of Nrf2 activators with planned exposures to cisplatin.

  6. Changes of spontaneous parthenogenetic activation and development potential of golden hamster oocytes during the aging process.

    Science.gov (United States)

    Jiang, Han; Wang, Ce; Guan, Jiyu; Wang, Lingyan; Li, Ziyi

    2015-01-01

    The golden hamster is an excellent animal experimental model for oocyte research. The hamster oocytes are very useful in clinical examination of human spermatozoan activity. Non-fertile oocytes can lead to time-dependent processes of aging, which will affect the results of human spermatozoa examination. As a consequence there is a need to investigate the aging and anti-aging processes of golden hamster oocytes. In order to study the aging processes and parthenogenetic activation of golden hamster oocytes, in vivo oocytes, oocytes cultured with or without cumulus cells, and oocytes treated with Trichostatin A (TSA) or caffeine were collected and investigated. We found that: (1) spontaneous parthenogenetic activation, developmental potential (cleavage rate), and zona pellucida (ZP) hardening undergo age-dependent changes in in vivo, in vitro, and after TSA or caffeine treatment; (2) in vivo, oocytes became spontaneously parthenogenetic 25 h post-hCG treatment; (3) in vitro, cumulus cells did not significantly increase the parthenogenetic activation rate of cultured hamster oocytes; and (4) TSA or caffeine could delay spontaneous oocyte parthenogenetic activation and the aging processes by at least 5h, but also accelerated the hardening of the ZP. These results define the conditions for the aging and anti-aging processes in golden hamster oocytes. TSA and caffeine play roles in controlling spontaneous activation, which could facilitate the storage and use of golden hamster oocytes for studying processes relevant to human reproduction. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yuni; Xu, Youhua; Shen, Yali; Wang, Cuicui; Guo, Gaili; Hu, Tiantian [Key Laboratory of Developmental Diseases in Childhood, Chongqing (China); Key Laboratory of Pediatrics in Chongqing, Chongqing (China); Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing (China)

    2012-02-17

    The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As{sub 2}O{sub 3}) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As{sub 2}O{sub 3}, and 300 µg/mL TMP combined with 0.5 µM As{sub 2}O{sub 3}, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright's staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As{sub 2}O{sub 3} alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As{sub 2}O{sub 3} treatment versus almost a 13-fold increase in the TMP + As{sub 2}O{sub 3} group. Cells treated with both TMP and As{sub 2}O{sub 3} expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As{sub 2}O{sub 3}-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As{sub 2}O{sub 3} has significant synergistic effects on the proliferative inhibition of HL-60 cells.

  8. [Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].

    Science.gov (United States)

    Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O

    2013-09-01

    To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  9. T1 mapping of the ischemic myocardium: Review of potential clinical use

    Energy Technology Data Exchange (ETDEWEB)

    Baxa, Jan, E-mail: baxaj@fnplzen.cz [Department of Imaging Methods, Faculty of Medicine in Pilsen, Charles University in Prague and University Hospital Pilsen (Czech Republic); Ferda, Jiří [Department of Imaging Methods, Faculty of Medicine in Pilsen, Charles University in Prague and University Hospital Pilsen (Czech Republic); Hromádka, Milan [Department of Cardiology, University Hospital Pilsen (Czech Republic)

    2016-10-15

    Highlights: • T1 mapping is a feasible method for detailed characterization of the myocardium. • Non-contrast T1 mapping has potential for precise quantification of myocardial edema in acute infarction. • Evaluation of non-contrast T1 maps and extracellular volume improve detection of the area at risk and final infarct size. • T1 mapping could be beneficial in the quantification of chronic fibrous scar of the myocardium. - Abstract: Cardiac magnetic resonance imaging (CMR) is an indispensable part of the diagnostic algorithm in cardiology. CMR has become a gold standard in various disorders; moreover, it is well established also as a surrogate end-point in experimental and clinical studies. Particularly, the ability to directly display myocardial injury is a unique feature in comparison with other methods. The mapping of magnetic relaxation properties (T1, T2 and T2* relaxation times) are still relatively new techniques, but promising to improve the robustness of CMR and add new appropriate indications. The high potential of T1 mapping in the diagnostic of myocardial ischemic involvement has been highlighted in several experimental and clinical studies, but the use in clinical routine was limited due to the shortcomings in scanning and image evaluation. However, the quantitative technique of T1 mapping is now commercially available and its simple use, good reproducibility and limited subjectivity allow its incorporation into routine CMR protocols. This review article is aimed to summarise existing results and clinical experience with T1 mapping in patients with ischemic cardiac disease.

  10. Types, Prevalence, and Potential Clinical Significance of Medication Administration Errors in Assisted Living

    Science.gov (United States)

    Young, Heather M.; Gray, Shelly L.; McCormick, Wayne C.; Sikma, Suzanne K.; Reinhard, Susan; Trippett, Linda Johnson; Christlieb, Carol; Allen, Tiffany

    2008-01-01

    OBJECTIVES To describe the types and potential clinical significance of medication administration errors in assisted living (AL). DESIGN Cross-sectional observational study. SETTING This study was conducted in 12 AL settings in three states (Oregon, Washington, and New Jersey). PARTICIPANTS Participants included 29 unlicensed assistive personnel and 510 AL residents. MEASUREMENTS Medication administration observations, chart review, and determination of rates, types, and potential clinical significance of errors using standardized methodology. RESULTS Of 4,866 observations, 1,373 errors were observed (28.2% error rate). Of these, 70.8% were wrong time, 12.9% wrong dose, 11.1% omitted dose, 3.5% extra dose, 1.5% unauthorized drug, and 0.2% wrong drug. Excluding wrong time, the overall error rate dropped to 8.2%. Of the 1,373 errors, three were rated as having potential clinical significance. CONCLUSION A high number of daily medications are given in AL. Wrong time accounted for the majority of the errors. The bulk of the medications are low risk and routine; to promote optimal care delivery, clinicians need to focus on high-risk medications and residents with complex health problems. PMID:18482296

  11. Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro

    Directory of Open Access Journals (Sweden)

    Lalita Subedi

    2017-02-01

    Full Text Available Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max as primary isoflavones, possess anti‐inflammatory activity, but the effect of its active metabolite Equol (7‐hydroxy‐3‐(4′‐hydroxyphenyl‐chroman has not been well established. In this study, we investigated the anti‐neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS cells, including microglia (BV‐2, astrocytes (C6, and neurons (N2a, were used. Effects of Equol on the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase (COX‐2, Mitogen activated protein kinase (MAPK signaling proteins, and apoptosis‐related proteins were measured by western blot analysis. Equol inhibited the lipopolysaccharide (LPS‐induced TLR4 activation, MAPK activation, NF‐kB‐mediated transcription of inflammatory mediators, production of nitric oxide (NO, release of prostaglandin E2 (PGE‐2, secretion of tumor necrosis factor‐α (TNF‐α and interleukin 6 (IL‐6, in Lipopolysaccharide (LPS‐activated murine microglia cells. Additionally, Equol protects neurons from neuroinflammatory injury mediated by LPS‐activated microglia through downregulation of neuronal apoptosis, increased neurite outgrowth in N2a cell and neurotrophins like nerve growth factor (NGF production through astrocytes further supporting its neuroprotective potential. These findings provide novel insight into the anti‐neuroinflammatory effects of Equol on microglial cells, which may have clinical significance in cases of neurodegeneration.

  12. High active potential antimycobacterial agents against Mycobacterium avium.

    Science.gov (United States)

    Karel, Waisser; Jiří, Kuneš; Jiřina, Stolaříková

    2012-06-01

    Derivatives of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dione are active against Mycobacterium avium when substituted in position 7 with a methyl. One or two carbonyl groups have to be replaced with a thioxo group. High active derivatives are the compounds without substitution on the phenyl, or those substituted on the phenyl in position 3 or 4 with chlorine, bromine or a methyl. The substitution in position 3 and 4 with two atoms of chlorine lowers the activity. The compounds are active against INH resistant strains. We synthesized other 44 derivatives with a similar structure of the compounds as in the paper but substituted in position 7 with other substituents (chlorine, bromine methoxy). The activity against M. avium was poor. It can be concluded that a new group of compounds with an excellent activity against M. avium has been found.

  13. Antibacterial activity of Artemisia nilagirica leaf extracts against clinical and phytopathogenic bacteria.

    Science.gov (United States)

    Ahameethunisa, Abdul R; Hopper, Waheeta

    2010-01-29

    The six organic solvent extracts of Artemisia nilagirica were screened for the potential antimicrobial activity against phytopathogens and clinically important standard reference bacterial strains. The agar disk diffusion method was used to study the antibacterial activity of A. nilagirica extracts against 15 bacterial strains. The Minimum Inhibitory Concentration (MIC) of the plant extracts were tested using two fold agar dilution method at concentrations ranging from 32 to 512 microg/ml. The phytochemical screening of extracts was carried out for major phytochemical derivatives in A. nilagirica. All the extracts showed inhibitory activity for gram-positive and gram-negative bacteria except for Klebsiella pneumoniae, Enterococcus faecalis and Staphylococcus aureus. The hexane extract was found to be effective against all phytopathogens with low MIC of 32 microg/ml and the methanol extract exhibited a higher inhibition activity against Escherichia coli, Yersinia enterocolitica, Salmonella typhi, Enterobacter aerogenes, Proteus vulgaris, Pseudomonas aeruginosa (32 microg/ml), Bacillus subtilis (64 microg/ml) and Shigella flaxneri (128 microg/ml). The phytochemical screening of extracts answered for the major derivative of alkaloids, amino acids, flavonoids, phenol, quinines, tannins and terpenoids. All the extracts showed antibacterial activity against the tested strains. Of all, methanol and hexane extracts showed high inhibition against clinical and phytopathogens, respectively. The results also indicate the presence of major phytochemical derivatives in the A. nilagirica extracts. Hence, the isolation and purification of therapeutic potential compounds from A. nilagirica could be used as an effective source against bacterial diseases in human and plants.

  14. [Prioritization of non-recommended clinical activities in Primary Care].

    Science.gov (United States)

    García Mochon, L; Olry de Labry Lima, A; Bermudez Tamayo, C

    2017-12-07

    To prioritize non-recommended clinical activities in Primary Care (PC), from "Do not do" recommendations listed by the Sociedad Española de Medicina de Familia y Comunitaria (Semfyc), according to expert consensus (physicians, nurses and pharmacists). The consensus for the prioritization of non-recommended practices in PC was performed through an online procedure. We used as a base the list of "do not-do" recommendations of the SEMFYC. We asked the experts to prioritize practices that should be de-adopted in PC, based on four prioritization criteria: frequency of occurrence, cost of the activity, ease of disposal and damage caused, which were scored from one to five, according to their recommendation. Scores were summarized in median and quartile values. Two rounds were necessary to obtain a consensus. A modified e-Delphi technique was used. 34 experts (62%) participated in the first consultation round and prioritized 19 recommendations with a score = 3.5. These recommendations were again analyzed in a second round, in which 32 panelists agreed to prioritize 17 practices (13 related to prescription, three diagnostic tests, and one clinical analysis). The high priority list included seven practices with values = 4: 1) Prescription of a new drug in elderly patients without having reviewed the previous treatments; 2) Lipid-lowering drugs without calculating the overall cardiovascular risk; 3) Not systematically prescribing gastric protection with proton pump inhibitors to patients consuming Nonsteroidal anti-inflammatory drugs (NSAIDs); 4) Glucose self-analysis in non-insulinized type 2 diabetics; 5) Benzodiazepines in the long term; 6) Bisphosphonates in patients with low risk of fracture; and 7) Antibiotics in lower respiratory tract infections. This study provides information for the prioritization of 17 non-AP activities in which short-term de-adoption would significantly increase the efficiency of the public health system.

  15. Plasma viscosity: a potential predictor of both medical treatment response and clinical stage of ulcerative colitis.

    Science.gov (United States)

    Yakar, Tolga; Cosar, Arif Mansur; Gokturk, Huseyin Savas; Kanat, Unler Gurhan; Parlakgumus, Alper; Kozanoglu, Iknur; Serin, Ender

    2016-01-01

    Ulcerative colitis (UC) is one of the major forms of chronic relapsing inflammatory bowel diseases. The ability to identify type, severity and responsiveness to therapy of UC using laboratory parameters has long been the aim of clinical studies. The aim of this study was to assess the relation betweenplasma viscosity (PV) and disease activity and response to medical treatment in patients with UC. The study included 105 patients with UC and 42 healthy volunteers. Blood samples were assessed for PV, erythrocyte sedimentation rate (ESR), high sensitive C-reactive protein (hs-CRP), D-dimer, and fibrinogen. Patients with UC were grouped according to disease activity, i.e. active (n= 59) and remission (n= 46). PV was higher in those with active UC compared with those with UC in remission or healthy subjects. It was significantly higher in both UC refractory to steroid compared to UC responsive to steroid (pUC refractory to cyclosporine compared to UC responsive cyclosporine (p= 0.003). IncreasedSimple Clinical Colitis Activity Index (SCCAI), Endoscopic Grading Scale (EGS), and Histological Disease Activity (HAD) scores were significantly associated with higher PV in patients with UC. PV is a useful marker in predicting response to steroid or cyclosporine treatment in patients with active UC. It could be replaced by ESR or hs-CRP as a measure of the acute phase response in UC since it is sufficiently sensitive. These findings may help identify patients with active UC who will require colectomy. Biomarkers, Disease activity, Medical treatment, Steroid-refractory ulcerative colitis, Ulcerative colitis.

  16. Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath.

    Science.gov (United States)

    Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina

    2016-01-01

    Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.

  17. Modeling Clinically Validated Physical Activity Assessments Using Commodity Hardware.

    Science.gov (United States)

    Winfree, Kyle N; Dominick, Gregory

    2018-03-01

    Consumer-grade wearable activity devices such as Fitbits are increasingly being used in research settings to promote physical activity (PA) due to their low-cost and widespread popularity. However, Fitbit-derived measures of activity intensity are consistently reported to be less accurate than intensity estimates obtained from research-grade accelerometers (i.e., ActiGraph). As such, the potential for using a Fitbit to measure PA intensity within research contexts remains limited. This study aims to model ActiGraph-based intensity estimates from the validated Freedson vector magnitude (VM3) algorithm using measures of steps, metabolic equivalents, and intensity levels obtained from Fitbit. Minute-level data collected from 19 subjects, who concurrently wore the ActiGraph GT3X and Fitbit Flex devices for an average of 1.8 weeks, were used to generate the model. After testing several modeling methods, a naïve Bayes classifier was chosen based on the lowest achieved error rate. Overall, the model reduced Fitbit to ActiGraph errors from 19.97% to 16.32%. Moreover, the model reduced misclassification of Fitbit-based estimates of moderate-to-vigorous physical activity (MVPA) by 40%, eliminating a statistically significant difference between MVPA estimates derived from ActiGraph and Fitbit. Study findings support the general utility of the model for measuring MVPA with the Fitbit Flex in place of the more costly ActiGraph GT3X accelerometer for young healthy adults.

  18. Increasing the clinical efficacy of NK and antibody-mediated cancer immunotherapy: potential predictors of successful clinical outcome observed in high-risk neuroblastoma

    Directory of Open Access Journals (Sweden)

    Tony A. Koehn

    2012-05-01

    Full Text Available Disease recurrence is frequent in high-risk neuroblastoma (NBL patients even after multimodality aggressive treatment [a combination of chemotherapy, surgical resection, local radiation therapy, autologous stem cell transplantation (ASCT and cis-retinoic acid (CRA]. Recent clinical studies have explored the use of monoclonal antibodies (mAbs that bind to disialoganglioside (GD2, highly expressed in NBL, as a means to enable immune effector cells to destroy NBL cells via antibody-dependent cell-mediated cytotoxicity (ADCC. Preclinical data indicate that ADCC can be more effective when appropriate effector cells are activated by cytokines. Clinical studies have pursued this by administering anti-GD2 mAb in combination with ADCC-enhancing cytokines (IL2 and GM-CSF, a regimen that has demonstrated improved cancer-free survival. More recently, early clinical studies have used a fusion protein that consists of the anti-GD2 mAb directly linked to IL2, and antitumor responses were seen in the Phase II setting. Analyses of genes that code for receptors that influence ADCC activity and Natural Killer (NK cell function [Fc Receptor (FcR, Killer Immunoglublin-like Receptor (KIR, and KIR-ligand (KIR-L] suggest patients with antitumor activity are more likely to have certain genotype profiles. Further analyses will need to be conducted to determine whether these genotypes can be used as predictive markers for favorable therapeutic outcome, thus potentially increasing the efficacy of mAb-mediated NK cell-based cancer immunotherapy.

  19. Activity theory as a potential framework for technology research in ...

    African Journals Online (AJOL)

    of the activity system leads to shifts at all levels of the system. I conclude by arguing that the strength of Activity Theory lies in its ability to enable one to understand learning as the complex result of tool mediated interactions, rather than as something opaque, which happens in a student's mind. South African Journal of ...

  20. The Potential for Development of Russian Youth Social Activity

    Directory of Open Access Journals (Sweden)

    Savotina Nataliya

    2016-03-01

    Full Text Available The article deals with scientific and applied topicality of studying the problem of children and youth social activity. Spheres of social activity display in European tradition, in particular, the European Charter, Great Britain, have been revealed. Comparative analysis of understanding the essence of such a phenomenon in Western theories and scientific pedagogical thought in Russia has been given. The changes occurred in the context of the analysis of the notion during last decades and connected with the development of volunteering, motivation and forms of youth services have been emphasized. The most important tasks in developing social activity of Russian youth have been stated. Different scientific approaches to studying the notion of “social activity” enriching its characteristics have been analyzed. Based on the analysis of results on the organized events the drawbacks, neglects and causes of poor quality of working on the development of youth social activity have been shown. The experience in choosing activities and technologies demonstrated by teachers and pupils from different regions of Russia has been presented. Theoretical analysis of foreign and domestic experience in education has enabled to offer suggestions for the expansion of pupils and students’ social activity in the frame of different models presenting a wide scope for mastering and developing social competency of children and youth. These models have become the foundation for creating a general algorithm for the expansion of children and youth social activity. Pedagogical conditions and perspective directions for solving the problem of social activity development have been outlined in the article.

  1. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

  2. Mitochondrial ROS potentiates indirect activation of the AIM2 inflammasome

    Directory of Open Access Journals (Sweden)

    Deborah D Crane

    2014-08-01

    Full Text Available Activation of the inflammasome is important for the detection and clearance of cytosolic pathogens. In contrast to avirulent F. novicida (Fn, infection with virulent F. tularensis ssp tularensis does not trigger activation of the host AIM2 inflammasome. Here we show that differential activation of AIM2 following Francisella infection is due to sensitivity of each isolate to reactive oxygen species (ROS. ROS present at the outset of Fn infection contributes to activation of the AIM2 inflammasome, independent of NLRP3 and NADPH oxidase. Rather, mitochondrial ROS (mROS is critical for Fn stimulation of the inflammasome. This study represents the first demonstration of the importance of mROS in the activation of the AIM2 inflammasome by bacteria. Our results also demonstrate that bacterial resistance to mROS is a mechanism of virulence for early evasion of detection by the host.

  3. Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2014-11-01

    The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

  4. Australian emergency clinicians' perceptions and use of the GIVE Clinical Trigger for identification of potential organ and tissue donors.

    Science.gov (United States)

    Neate, Sandra; Marck, Claudia H; Weiland, Tracey J; Cunningham, Nicola; Hickey, Bernadette B; Dwyer, Bernadine M; Jelinek, George A

    2012-10-01

    In 2010 the Australian Organ and Tissue Authority introduced a nationally consistent indicator, the GIVE Clinical Trigger, for early identification of potential organ and tissue donors in EDs and intensive care units. This national survey of emergency clinicians aimed to assess emergency clinicians' perceptions and use of the Trigger. National cross-sectional survey of Australasian College for Emergency Medicine (ACEM) fellows and trainees and members of the College of Emergency Nursing Australia (CENA); online questionnaire; 12 items addressing implementation of the GIVE Trigger; graded and free-text responses. Five hundred and ninety-nine (20.2%) of 2969 ACEM members and 212 (20.7%) of 1026 CENA members responded. Four hundred and seventy-four respondents (62.7%) were familiar with the Trigger; 472 (63.8%) agreed it was easy to recognise patients who activated the Trigger; 490 (64.9%) had sufficient time to use the Trigger; 511 (67.7%) felt they had the necessary competence and knowledge to identify a potential donor; 464 (61.5%) felt competent and 501 (66.4%) felt comfortable referring a potential donor when identified. Overall 587 (77.7%) ED clinicians supported the use of the Trigger, but most (587 [77.7%]) perceived barriers to its use; 628 (80%) had never activated the Trigger and 557 (71%) had never referred a potential donor to relevant authorities. Most Australian emergency clinicians are familiar with and support the GIVE Clinical Trigger, and feel they have the necessary skills to use the Trigger; however, most perceive barriers to its use and have not yet used the Trigger. © 2012 The Authors. EMA © 2012 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  5. Crystalline Nanosuspensions as Potential Toxicology and Clinical Oral Formulations for BCS II/IV Compounds

    OpenAIRE

    Kesisoglou, Filippos; Mitra, Amitava

    2012-01-01

    Nanosuspensions, formulations based on the reduction of the active pharmaceutical ingredient (API) particle size in the sub-micron range and most typically around 100–200 nm, represent a valuable option for formulators to facilitate oral absorption of Biopharmaceutics Classification System class II and IV compounds. Their ability to increase the API dissolution rate and subsequent absorption and thus oral bioavailability has been demonstrated in preclinical and clinical settings. This review ...

  6. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    International Nuclear Information System (INIS)

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-01-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  7. Potential antifungal activity of Cladonia aff. rappii A. Evans

    Directory of Open Access Journals (Sweden)

    Claudia M. Plaza

    2017-10-01

    Full Text Available Context: Lichen is a self-supporting symbiotic organism composed of a fungus and an algal partner. They have manifold biological activities like antiviral, antibiotic, antioxidant, antitumor, allergenic and inhibition of plant growth. Species of Cladonia, have been studied by its antifungal activity. Aims: To evaluate the antifungal activity determination of Cladonia aff. rappii against five yeasts, four of genus Candida and one Cryptococcus, using water, ethanol and dichloromethane extracts. Methods: The evaluation of the antifungal activity was developed by three diffusion methods such as spot-on-a-lawn, disc diffusion and well diffusion. Additionally, the values of minimal inhibitory concentration (MIC and the minimum fungicidal concentration (MFC were determined. Results: Based on the experimental results obtained, the best antifungal activity was using ethanol extract at 20 mg/mL against Candida albicans, applying the three diffusion methods above mentioned. With ethanol extract, the lower MIC was against Candida glabrata and the lower MFC were with Candida glabrata, C. krusei, C. parapsilosis and C. tropicalis. The dichloromethane extract presented the lowest MIC and MFC against C. neoformans. Not activity was observed with aqueous extract. Conclusions: The present study revealed antifungal and fungicidal activity in the extract of lichen Cladonia aff. rappii.

  8. Clinical research in dermatology: resources and activities associated with a higher scientific productivity.

    Science.gov (United States)

    Molina-Leyva, Alejandro; Descalzo, Miguel A; García-Doval, Ignacio

    2018-03-06

    Clinical research papers and their derived metrics can be useful to assess the scientific production of medical and research centers. Diverse factors are probably associated to differences in scientific production. But there are scarce studies analyzing them. Resources are limited and have to be distributed efficiently. The objective of this study is to explore what resources and activities are potentially associated with a higher scientific productivity. A bibliometric study was performed to obtain information about scientific productivity. Papers included had to meet criteria to be considered clinical research in dermatology, additionally had to be published between the years 2005-2014, had to be included in Pubmed or Embase and had to include a Spanish center of dermatology as the correspondence address. Information about research resources and activities of the year 2015 was gathered by means of an online survey sent to the authors identified in the bibliometric study. The search strategy returned 8617 papers and only 1104 of them (12.81%) met the inclusion criteria. 63 out of 113 centers responded to the survey (55.75%). Factors associated with a higher scientific productivity were: the size of the resident program, the amount of time specifically dedicated to research, a lower clinical workload, and the number of clinical trials performed in the last year. We have demonstrated that some factors are associated with a higher scientific productivity. Residency program, more research staff, clinical workload redistribution and research motivation/initiatives are key strategies that could improve scientific productivity of a center.

  9. Clinical applications of in vivo neutron-activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cohn, S.H.

    1982-01-01

    In vivo neutron activation has opened a new era of both clinical diagnosis and therapy evaluation, and investigation into and modelling of body composition. The techniques are new, but it is already clear that considerable strides can be made in increasing accuracy and precision, increasing the number of elements susceptible to measurement, enhancing uniformity, and reducing the dose required for the measurement. The work presently underway will yield significant data on a variety of environmental contaminants such as Cd. Compositional studies are determining the level of vital constituents such as nitrogen and potassium in both normal subjects and in patients with a variety of metabolic disorders. Therapeutic programs can be assessed while in progress.

  10. In-vivo neutron activation analysis: principles and clinical applications

    International Nuclear Information System (INIS)

    Cohn, S.H.

    1982-01-01

    In vivo neutron activation has opened a new era of both clinical diagnosis and therapy evaluation, and investigation into and modelling of body composition. The techniques are new, but it is already clear that considerable strides can be made in increasing accuracy and precision, increasing the number of elements susceptible to measurement, enhancing uniformity, and reducing the dose required for the measurement. The work presently underway will yield significant data on a variety of environmental contaminants such as Cd. Compositional studies are determining the level of vital constituents such as nitrogen and potassium in both normal subjects and in patients with a variety of metabolic disorders. Therapeutic programs can be assessed while in progress. It seems likely that by the end of this century there will have been significant progress with this research tool, and exciting insights obtained into the nature and dynamics of human body composition

  11. Mesenchymal Stem Cells and Metabolic Syndrome: Current Understanding and Potential Clinical Implications

    Directory of Open Access Journals (Sweden)

    Kenichi Matsushita

    2016-01-01

    Full Text Available Metabolic syndrome is an obesity-based, complicated clinical condition that has become a global epidemic problem with a high associated risk for cardiovascular disease and mortality. Dyslipidemia, hypertension, and diabetes or glucose dysmetabolism are the major factors constituting metabolic syndrome, and these factors are interrelated and share underlying pathophysiological mechanisms. Severe obesity predisposes individuals to metabolic syndrome, and recent data suggest that mesenchymal stem cells (MSCs contribute significantly to adipocyte generation by increasing the number of adipocytes. Accordingly, an increasing number of studies have examined the potential roles of MSCs in managing obesity and metabolic syndrome. However, despite the growing bank of experimental and clinical data, the efficacy and the safety of MSCs in the clinical setting are still to be optimized. It is thus hoped that ongoing and future studies can elucidate the roles of MSCs in metabolic syndrome and lead to MSC-based therapeutic options for affected patients. This review discusses current understanding of the relationship between MSCs and metabolic syndrome and its potential implications for patient management.

  12. Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

    International Nuclear Information System (INIS)

    Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

    2004-01-01

    The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

  13. Standards in clinical decision support: activities in health level seven.

    Science.gov (United States)

    Jenders, Robert A; Jenders, Robert Allen; Del Fiol, Guilherme; Kawamoto, Kensaku; Sailors, R Matthew

    2008-11-06

    Health Level Seven (HL7) has evolved into an international standards development organization (SDO) with a suite of standards. Prominent among these are formalisms related to clinical decision support, including the Arden Syntax, GELLO and Decision Support Service (DSS) standards. Continuing improvement in these standards and ongoing development of future decision support standards require wide participation in order to maximize their success. Accordingly, the purpose of the workshop is twofold. First, instructors will convey the latest developments regarding existing decision support standards and related efforts to develop new standards. Second, the instructors will solicit feedback so that attendees who do not participate in HL7 can have input into the standards activities of that organization. The instructors of this workshop, who are the co-chairs and/or members of the Clinical Decision Support Technical Committee of HL7, will review progress in these areas. They will present the details of the ongoing development of the extant Arden Syntax, GELLO and DSS standards. They will discuss work on current draft and proposed future standards, including the Infobutton communication and Order Set standards that are undergoing development in anticipation of certification as standards. Finally, they will solicit discussion regarding the future direction of standards development in these areas.

  14. Potential Risks and Mitigation Strategies During the Conduct of a Clinical Trial: An Industry Perspective.

    Science.gov (United States)

    Bhagat, Seema; Kapatkar, Vaibhavi; Katare, Sagar; Mane, Ashish; Pinto, Colette; Pawar, Kedar; Shah, Agam; Barkate, Hanmant

    2018-01-31

    Every phase of a clinical trial should be designed in compliance with good clinical practices by following all relevant regulatory guidelines. Patient safety, data integrity and ethics are an integral part of a successful clinical trial which must be considered. Therefore, risk monitoring is an essential tool to identify the risks associated with conduct of any trial. This article is a result of extensive research conducted by a reputed pharmaceutical company to identify the potential stages of risks associated with the conduct phase of trial that could impact the overall quality and safety of a trial. The skillful and experienced team members of a reputed pharmaceutical company involved in conducting clinical trials underwent brainstorming sessions to assess and categorize the risks associated with each stage of conduct phase of a clinical trial. They also developed a mitigation plan based on their experiences, best practices and applicable guidance documents. During conduct phase, risks are associated with preparation of site master and trial master file, courier of study supply to site(s) including investigational product prior to site initiation visit, patient recruitment, telephonic monitoring, adverse or serious adverse event monitoring, site monitoring visit(s), collected case report form pages forward to data management vendor, data query clarification and site close-out visit. A close working relationship with all the persons associated with the clinical trial, timely monitoring and prospective mitigation planning is required for the conduct of a high quality trial. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Kaplan P

    2014-05-01

    counts, and bone density, as well as decreases in biomarkers of Gaucher disease activity. Few adverse events, none of which was serious, have been reported. Eliglustat tartrate has the clinical potential to enable a larger number of patients with type 1 Gaucher disease to be treated successfully.Keywords: type 1 Gaucher disease, substrate reduction therapy, eliglustat tartrate

  16. Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction

    Directory of Open Access Journals (Sweden)

    Poulsen JL

    2014-09-01

    Full Text Available Jakob Lykke Poulsen,1 Christina Brock,1,2 Anne Estrup Olesen,1,2 Matias Nilsson,1 Asbjørn Mohr Drewes1,3 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAbstract: Opioid-induced bowel dysfunction (OIBD is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption and oxycodone in a combined tablet. Another approach is peripherally acting, µ-opioid receptor antagonists (PAMORAs that selectively target µ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential

  17. Transforming growth factor β activated kinase 1: a potential therapeutic target for rheumatic diseases.

    Science.gov (United States)

    Fechtner, Sabrina; Fox, David A; Ahmed, Salahuddin

    2017-07-01

    Pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α are central regulators of autoinflammatory diseases. While targeting these cytokines has proven to be a successful clinical strategy, the long-term challenges such as drug resistance, lack of efficacy and poor clinical outcomes in some patients are some of the limitations faced by these therapies. This has ignited strategies to reduce inflammation by potentially targeting a variety of molecules, including cell surface receptors, signalling proteins and/or transcription factors to minimize cytokine-induced inflammation and tissue injury. In this regard, transforming growth factor β activated kinase 1 (TAK1) is activated in the inflammatory signal transduction pathways in response to IL-1β, TNF-α or toll-like receptor stimulation. Because of its ideal position upstream of mitogen-activated protein kinases and the IκB kinase complex in signalling cascades, targeting TAK1 may be an attractive strategy for treating diseases characterized by chronic inflammation. Here, we discuss the emerging role of TAK1 in mediating the IL-1β, TNF-α and toll-like receptor mediated inflammatory responses in diseases such as RA, OA, gout and SS. We also review evidence suggesting that TAK1 inhibition may have potential therapeutic value. Finally, we focus on the current status of the development of TAK1 inhibitors and suggest further opportunities for testing TAK1 inhibitors in rheumatic diseases. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

    Science.gov (United States)

    Campos-Parra, Alma D.; Cuamani Mitznahuatl, Gerardo; Pedroza-Torres, Abraham; Vázquez Romo, Rafael; Porras Reyes, Fany Iris; López-Urrutia, Eduardo; Pérez-Plasencia, Carlos

    2017-01-01

    Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC. PMID:28574440

  19. Potential Role of Activated Nonparenchymal Cells in Acetaminophen-Induced Potentiation of Hepatotoxicity

    Science.gov (United States)

    1991-06-14

    Acute Liver Necrosis Following Overdose of Paracetamol . British Medical Journal. 2: 497-499. Decker, T., M. L. Lohmann-Matthes, U. Karck, T. Peters...Lyon and R. Williams. 1975. Histopathological Changes in the Liver Following Paracetamol Overdose : Correlation with Clinical and 152 Biochemical... Paracetamol Hepatotoxicity: IN VITRO Studies in Isolated Mouse Hepatocytes. Toxicology Letters. 2229: 37-48. Casini, A. M., P. A. Ferrali and M

  20. Correlation between Histological Activity and Endoscopic, Clinical, and Serologic Activities in Patients with Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Dae Bum Kim

    2016-01-01

    Full Text Available Objectives. Recent studies suggest that histological healing is a treatment goal in ulcerative colitis (UC. We aimed to evaluate the correlation between histological activity and clinical, endoscopic, and serologic activities in patients with UC. Methods. We retrospectively reviewed medical records from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsies. The Mayo endoscopic subscore was used to assess endoscopic activity. Biopsy specimens were reviewed by two blinded pathologists and scored using the Geboes scoring system. Results. We analyzed 154 biopsy specimens from 82 patients with UC. Histological scores exhibited strong correlation with endoscopic subscores (Spearman’s rank correlation coefficient r=0.774, p<0.001 and moderate correlation with C-reactive protein levels (r=0.422, p<0.001 and partial Mayo scores (r=0.403, p<0.001. Active histological inflammation (Geboes score ≥ 3.1 was observed in 6% (2 of 33 of the endoscopically normal mucosa samples, 66% (19 of 29 of mild disease samples, and 98% (90 of 92 of moderate-to-severe disease samples. Conclusions. Histological activity was closely correlated with the endoscopic, clinical, and serologic UC activities. However, several patients with mild or normal endoscopic findings exhibited histological evidence of inflammation. Therefore, histological assessment may be helpful in evaluating treatment outcomes and determining follow-up strategies.

  1. PATIENTS WITH SUSPECTED METAL IMPLANT ALLERGY: POTENTIAL CLINICAL PICTURES AND ALLERGOLOGICAL DIAGNOSTIC APPROACH (REVIEW

    Directory of Open Access Journals (Sweden)

    P. Thomas

    2014-01-01

    Full Text Available The focus of this review are allergic complications following insertion of metallic orthopedic implants. Such potential allergic reactions encompass eczema, impaired wound and fracture healing, infection-mimicking reactions, effusions, pain and loosening. Nickel, cobalt and chromium seem to be the predominant eliciting allergens. Allergy might be considered prior to planned orthopaedic surgery or in patients with complications following arthroplasty We recommend, that differential diagnoses - in particular infection -should always be excluded in cooperation with surgery collegues. The clinical work up of a patient suspected of suffering from metal implant allergy should include a combined evaluation of medical history, clinical findings, patch testing and histology In vitro testing, namely the lymphocyte transformation test (LTT, can indicate metal sensitization, but needs careful interpretation.

  2. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  3. Clearance potential of ITER vacuum vessel activated materials

    International Nuclear Information System (INIS)

    Cepraga, D.G.; Cambi, G.; Frisoni, M.

    2002-01-01

    To demonstrate fusion's environmental attractiveness over the entire life cycle, a waste analysis is mandatory. The clearance is recommended by IAEA for releasing activated solid materials from regulatory control and for waste management policy. The paper focuses on the approach used to support waste analyses for ITER Generic Site Safety Report. The Material Unconditional Clearance Index of all the materials/zones on the equatorial mid-plane of ITER machine have been evaluated, based on IAEA-TECDOC-855. The Bonami-Nitawl-XSDNRPM sequence of the Scale-4.4a code system (using Vitenea-J library) has been firstly used for radiation transport analyses. Then the Anita-2000 code package is used for the activation calculation. The paper presents also, as an example, an application of the clearance indexes estimation for the ITER vacuum vessel materials. The results of the Anita-2000 have been compared with those obtained using the Fispact-99 activation code. (author)

  4. Relations between active bacteria and heterotrophic potential in the sea

    International Nuclear Information System (INIS)

    Hoppe, H.G.

    1978-01-01

    Measurements of heterotrophic substrate uptake and turnover rates of water-soluble substances suggest that these parameters are closely related to the degree of eutrophication of a water body. Respiration ratios (i.e. the respired fraction of the gross uptake) of organic substances by heterotrophic bacteria seem to be very similar under different conditions. The efficiency of incorporation is considerably higher than in other organisms (e.g. 44% for aspartic acid, 72% for glucose). Organic substrates excreted by phytoplanktonic algae are a food source for the heterotrophs. Autoradiographic experiments demonstrate that mainly heterotrophic bacteria are responsible for the substrate uptake from the water, though common and dominant algal species in brackish water also show slight substrate uptake even at nearly natural substrate concentrations (30 μg C l -1 ). Free living bacteria, not forming colonies on routine agar media but actively metabolizing organic substrates, are predominant inhabitants of offshore marine regions. Average annual numbers of active bacteria in the western Baltic vary from 945000 ml -1 in polluted inshore to 450 000 ml -1 in unpolluted offshore waters. In summer up to 56% of the total bacterial flora is metabolically active, whereas in winter sometimes only about 10% shows detectable substrate uptake in autoradiographic experiments. Colony forming bacteria range from 0.01% to 12.5% of the actively metabolizing bacterial population. The predominant active bacterial flora is well-adapted to the seasonal changes of water temperature and the uptake velocity of tritiated substrates is correlated with the number of active cells. (Auth.)

  5. Clinical incidents involving students on placement: an analysis of incident reports to identify potential risk factors.

    Science.gov (United States)

    Gaida, J E; Maloney, S; Lo, K; Morgan, P

    2015-06-01

    Students are sometimes involved in incidents during clinical training. To the authors' knowledge, no quantitative studies of incidents specifically involving physiotherapy students on clinical placement are available in the literature. A retrospective audit (2008 to 2011) of incident reports involving physiotherapy students was conducted to identify the nature and features of incidents. The study aimed to determine if injuries to a student or patient were more or less likely when the supervisor was in close proximity, and whether students with lower academic performance in their preclinical semester were more likely to be involved in an incident. There were 19 care-delivery-related and three equipment-related incidents. There were no incidents of violent, aggressive or demeaning behaviour towards students. The incident rate was 9.0/100,000 student-hours for third-year students and 6.8/100,000 student-hours for fourth-year students. The majority of incidents (55%) occurred from 11 am to 12-noon and from 3 pm to 3.30 pm. Incidents more often resulted in patient or student injury when the supervisor was not in close proximity (approximately 50% vs approximately 20%), although the difference was not significant (P=0.336). The academic results of students involved in incidents were equivalent to the whole cohort in their preclinical semester {mean 75 [standard deviation (SD) 6] vs 76 (SD 7); P=0.488}. The unexpected temporal clustering of incidents warrants further investigation. Student fatigue may warrant attention as a potential contributor; however, contextual factors, such as staff workload, along with organisational systems, structures and procedures may be more relevant. The potential relationship between supervisor proximity and injury also warrants further exploration. The findings of the present study should be integrated into clinical education curricula and communicated to clinical educators. Copyright © 2014 Chartered Society of Physiotherapy. Published by

  6. Diagnostic accuracy of clinical and blood examination for sepsis in potentially infected neonates

    Directory of Open Access Journals (Sweden)

    Ari Mulyani

    2006-10-01

    Full Text Available Background Neonatal sepsis remains a diagnostic challenge due to its nonspesific symptoms and signs. Blood culture as the gold standard is still a problem because it takes time, is expensive, and not every health facility is able to perionn. Objective To evaluate the diagnostic accuracy of clinical symptoms, hematologic findings, and C-reactive protein (CRP in neonatal sepsis. Methods Samples were taken from potentially infected neonates admitted to the Matemal-Perinatal Unit of Sardjito Hospital, between December 1st, 2000 and March 31st, 2001 using at least one of the criteria: prematurity, very low birth weight infants, matemal pyrexia during delivery, premature membrane rupture, or thick, cloudy amniotic fluid. Clinical symptoms, total leukocyte, neutrophil, platelet count, CRP, and blood culture as the gold standard were examined. Results Among 99 neonates enrolled, the sensitivity, specificity, positive and negative predictive value of clinical symptoms were 79.3%, 75.7%, 57.5%, and 89.9%, respectively; leukopenia/leukocytosis were 27.6%, 85.7%, 44.4%, and 74.1%; neutropenia! neutrophilia were 41.4%, 71.4%, 37.5%, and 74.6%; thrombocytopenia were 79.3%, 51.8%, 40.4%, and 85.7%; positive CRP were 58.6%,78.6%,53.1%, and 82.1%. Parallel tests increased the sensitivity up to 89.7%. Specificity, positive and negative predictive value, and likelihood ratio were 44.3%, 40%, 91.2%, and 1.6, respectively. Serial tests increased the specificity up to 88.6%. Sensitivity, positive and negative predictive value, and likelihood ratio were 58.6%, 68%, 83.8%, and 5.1, respectively. Conclusion Clinical sepsis, thrombocytopenia, and CRP are sufficiently accurate as diagnostic tests for sepsis in potentially infected neonates. Parallel tests will increase the sensitivity, while serial tests increase the specificity.

  7. Activating the working behavior of citizens by motivation potential

    Directory of Open Access Journals (Sweden)

    Tatyana Nikolayevna Lobanova

    2015-03-01

    Full Text Available Objective to study the possibility to change the working behavior of employees by actualizing their motivational potential. Methods the methods of survey questionnaires focus groups coaching and interview were used in the study. Results the studies have shown that the employeesrsquo motivational potential is revealed through a complex system of labor motivation taking into account the needs and interests of a particular employee and forming the motivational and stimulating environment. Scientific novelty the research includes the development of methods to analyze the employeesrsquo interests and dominant motives and building of the structural system of employeesrsquo motivation to effective action. Practical value developing a method to increase the employeesrsquo motivation for efficient work in the form of a systematic set of actions. The application of this method allows to increase the efficiency and productivity of workers to gain additional profit which is especially important in the context of the economic crisis and the lack of additional investment. nbsp

  8. Medicinal plants with potential anti-arthritic activity:

    Directory of Open Access Journals (Sweden)

    Manjusha Choudhary

    2015-06-01

    Conclusion: This review clearly indicates that list of medicinal plants presented in this review might be useful to researchers as well as practioners. This review can be useful for preliminary screening of potential anti- arthritis plants. Further toxicity profile given in the review can be useful for the researchers for finding the safe dose. [J Intercult Ethnopharmacol 2015; 4(2.000: 147-179

  9. Radotinib and its clinical potential in chronic-phase chronic myeloid leukemia patients: an update.

    Science.gov (United States)

    Eskazan, Ahmet Emre; Keskin, Dilek

    2017-09-01

    Although imatinib has dramatically improved major outcomes in patients with chronic myeloid leukemia (CML), there are newer tyrosine kinase inhibitors (TKIs) approved worldwide for the treatment of resistant cases, and two second-generation TKIs (dasatinib, nilotinib) are approved in some nations for treating patients in the upfront setting. Radotinib (IY5511HCL, Supect® ) is a novel and selective second-generation BCR-ABL1 TKI, which is currently approved in Korea for the treatment of patients with CML both in the upfront and salvage settings. This review mainly focuses on the clinical potential of radotinib in patients with CML in chronic phase in terms of efficacy and safety.

  10. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

    Directory of Open Access Journals (Sweden)

    Dürsteler KM

    2015-06-01

    Full Text Available Kenneth M Dürsteler,1,2 Eva-Maria Berger,1 Johannes Strasser,1 Carlo Caflisch,2 Jochen Mutschler,2 Marcus Herdener,2 Marc Vogel1 1Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland; 2Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Background: Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH, as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim: To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods: We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results: MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and

  11. Potential serious bias in National Clinical Databases with low degree of reported follow-up

    DEFF Research Database (Denmark)

    Bjerre, J J; Jensen, P K; Sparsø, B H

    2017-01-01

    hospitals. We studied the patient files and compared them to figures reported to the DKRR. 92.5% of the operated patients was registered in DKRR. The 1-year follow-up rate reported to DKRR was 33.4%, and 14.5% filled in patient reported outcomes (KOOS and Tegner) at 1 year. Only 65% had actually been...... if patents are invited and reported. The unreported data is potentially a serious bias. It is suggested that data from clinics with low follow-up should not be used in studies involving outcomes based on national databases because of risk of bias....

  12. Lipolytic activity of potential probiotic enterococci and additive staphylococci

    Czech Academy of Sciences Publication Activity Database

    Simonová, M.; Sirotek, Kamil; Marounek, Milan; Lauková, A.

    2008-01-01

    Roč. 77, č. 5 (2008), s. 575-580 ISSN 0001-7213 Grant - others:Slovenská Akademie věd(SK) VEGA 2/0008/28 Institutional research plan: CEZ:AV0Z50450515 Keywords : bacteria * lipase * metabolic activity Subject RIV: GH - Livestock Nutrition Impact factor: 0.395, year: 2008

  13. Antiradical potential and antifungal activities of essential oils of the ...

    African Journals Online (AJOL)

    Investigations were conducted to determine the chemical composition, antiradical and antifungal activities of the essential oil extracted from the fresh leaves of Citrus latifolia var. Tahiti from Cameroon against Phaeoramularia angolensis. The essential oil obtained by hydrodistillation was analysed by GC and GC/MS.

  14. New Potentially Active Pyrazinamide Derivatives Synthesized Under Microwave Conditions

    Directory of Open Access Journals (Sweden)

    Ondrej Jandourek

    2014-07-01

    Full Text Available A series of 18 N-alkyl substituted 3-aminopyrazine-2-carboxamides was prepared in this work according to previously experimentally set and proven conditions using microwave assisted synthesis methodology. This approach for the aminodehalogenation reaction was chosen due to higher yields and shorter reaction times compared to organic reactions with conventional heating. Antimycobacterial, antibacterial, antifungal and photosynthetic electron transport (PET inhibiting in vitro activities of these compounds were investigated. Experiments for the determination of lipophilicity were also performed. Only a small number of substances with alicyclic side chain showed activity against fungi which was the same or higher than standards and the biological efficacy of the compounds increased with rising lipophilicity. Nine pyrazinamide derivatives also inhibited PET in spinach chloroplasts and the IC50 values of these compounds varied in the range from 14.3 to 1590.0 μmol/L. The inhibitory activity was connected not only with the lipophilicity, but also with the presence of secondary amine fragment bounded to the pyrazine ring. Structure-activity relationships are discussed as well.

  15. Potential Anticonvulsant Activity of Ethanol Extracts of Cichorium ...

    African Journals Online (AJOL)

    Received: 22 May 2015. Revised accepted: 19 August 2014. Abstract. Purpose: To evaluate the acticonvulsant activity of Cichorium intybus (C. intybus) and Taraxacum serotinum (T. serotinum) in maximal electroshock (MES), as well as pentylenetetrazole (PTZ)- and strychnine nitrate (STN) - induced seizure models in rats.

  16. Antibacterial activities and toxicological potentials of crude ethanolic ...

    African Journals Online (AJOL)

    SERVER

    2007-07-04

    Jul 4, 2007 ... Leaves of Euphorbia hirta used in traditional medicine for the treatments of boils, wounds and control of diarrhoea and dysentery were extracted by maceration in ethanol. The agar diffusion method was used to determine the antibacterial activity against Staphylococcus aureus, Escherichia coli,.

  17. The potential implication of eosinophil activation in the pathogenesis ...

    African Journals Online (AJOL)

    Ehab

    inflammation of the airways. Pulmonary function tests are less easily performed in young children. So, measuring markers of eosinophil activation is of special importance in pediatric practice. Objective: This study aimed at evaluating the role of eosinophil protein X. (EPX) as a marker for assessment of asthma attack severity ...

  18. In vitro assay of potential antifungal and antibacterial activities of ...

    African Journals Online (AJOL)

    ... the dermatophytes strains Trichophyton rubrum, Trichophyton interdigitale, Trichophyton soudanense, Microsporum langeronii, and Epidermophyton floccosum were used. The E2F2 extract showed strong inhibitory activity on four of the five fungal species used against ketoconazole, a standard antifungal drug. However ...

  19. The potential implication of eosinophil activation in the pathogenesis ...

    African Journals Online (AJOL)

    Background: Asthma is now recognized as an eosinophil mediated inflammation of the airways. Pulmonary function tests are less easily performed in young children. So, measuring markers of eosinophil activation is of special importance in pediatric practice. Objective: This study aimed at evaluating the role of eosinophil ...

  20. Antibacterial activities and toxicological potentials of crude ethanolic ...

    African Journals Online (AJOL)

    Leaves of Euphorbia hirta used in traditional medicine for the treatments of boils, wounds and control of diarrhoea and dysentery were extracted by maceration in ethanol. The agar diffusion method was used to determine the antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, ...

  1. Future electron accelerators and free electron lasers: Potentials in clinical medicine

    Science.gov (United States)

    Larsson, Börje; Stepanek, Jiri

    1997-10-01

    Studies of the biological and technical prerequisites for the clinical use of monoenergetic X-rays, and their specific absorption in heavy elements are conducted, with a view towards plans for stereotactic photon activation radiosurgery. The primary aim is the controlled eradication of target structures in the brain for the treatment of functional brain disorders or small brain tumours, with monochromatic synchrotron X-rays. The specific cell-killing action is based on DNA-breakage caused by short-range Auger and Coster-Kronig electrons produced by heavy atoms upon K-shell absorption of their characteristic X-rays. To this end, iodine or heavy metals would have to be deposited, in or close to nuclear DNA in target cells by means of suitable molecular vehicles. Practically useful concepts for clinically useful monoenergetic X-ray facilities and beam-lines are being developed. In this paper attention is focussed on the possible use of laser Compton backscattering for the production of clinically useful monochromatic X-ray beams suitable for irradiation of very small targets in the brain through the intact skull. Particularly relevant, in the present context are prospects for introducing free electron laser technology to improve the calculated parameters of X-ray beams designed for stereotactic photon activation radiosurgery with monochromatic photons in the energy interval 30-100 keV. Constructive initiatives would be welcome!

  2. A scoping review of the potential for chart stimulated recall as a clinical research method.

    Science.gov (United States)

    Sinnott, Carol; Kelly, Martina A; Bradley, Colin P

    2017-08-22

    Chart-stimulated recall (CSR) is a case-based interviewing technique, which is used in the assessment of clinical decision-making in medical education and professional certification. Increasingly, clinical decision-making is a concern for clinical research in primary care. In this study, we review the prior application and utility of CSR as a technique for research interviews in primary care. Following Arksey & O'Malley's method for scoping reviews, we searched seven databases, grey literature, reference lists, and contacted experts in the field. We excluded studies on medical education or competence assessment. Retrieved citations were screened by one reviewer and full texts were ordered for all potentially relevant abstracts. Two researchers independently reviewed full texts and performed data extraction and quality appraisal if inclusion criteria were met. Data were collated and summarised using a published framework on the reporting of qualitative interview techniques, which was chosen a priori. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines informed the review report. From an initial list of 789 citations, eight studies using CSR in research interviews were included in the review: six from North America, one from the Netherlands, and one from Ireland. The most common purpose of included studies was to examine the influence of guidelines on physicians' decisions. The number of interviewees ranged from seven to twenty nine, while the number of charts discussed per interview ranged from one to twelve. CSR gave insights into physicians' reasoning for actions taken or not taken; the unrecorded social and clinical influences on decisions; and discrepancies between physicians' real and perceived practice. Ethical concerns and the training and influence of the researcher were poorly discussed in most of the studies. Potential pitfalls included the risk of recall, selection and observation biases. Despite the proven validity

  3. Motor Unit Action Potential Clustering—Theoretical Consideration for Muscle Activation during a Motor Task

    Directory of Open Access Journals (Sweden)

    Michael J. Asmussen

    2018-01-01

    Full Text Available During dynamic or sustained isometric contractions, bursts of muscle activity appear in the electromyography (EMG signal. Theoretically, these bursts of activity likely occur because motor units are constrained to fire temporally close to one another and thus the impulses are “clustered” with short delays to elicit bursts of muscle activity. The purpose of this study was to investigate whether a sequence comprised of “clustered” motor unit action potentials (MUAP can explain spectral and amplitude changes of the EMG during a simulated motor task. This question would be difficult to answer experimentally and thus, required a model to study this type of muscle activation pattern. To this end, we modeled two EMG signals, whereby a single MUAP was either convolved with a randomly distributed impulse train (EMG-rand or a “clustered” sequence of impulses (EMG-clust. The clustering occurred in windows lasting 5–100 ms. A final mixed signal of EMG-clust and EMG-rand, with ratios (1:1–1:10, was also modeled. A ratio of 1:1 would indicate that 50% of MUAP were randomly distributed, while 50% of “clustered” MUAP occurred in a given time window (5–100 ms. The results of the model showed that clustering MUAP caused a downshift in the mean power frequency (i.e., ~30 Hz with the largest shift occurring with a cluster window of 10 ms. The mean frequency shift was largest when the ratio of EMG-clust to EMG-rand was high. Further, the clustering of MUAP also caused a substantial increase in the amplitude of the EMG signal. This model potentially explains an activation pattern that changes the EMG spectra during a motor task and thus, a potential activation pattern of muscles observed experimentally. Changes in EMG measurements during fatiguing conditions are typically attributed to slowing of conduction velocity but could, per this model, also result from changes of the clustering of MUAP. From a clinical standpoint, this type of muscle

  4. Motor Unit Action Potential Clustering—Theoretical Consideration for Muscle Activation during a Motor Task

    Science.gov (United States)

    Asmussen, Michael J.; von Tscharner, Vinzenz; Nigg, Benno M.

    2018-01-01

    During dynamic or sustained isometric contractions, bursts of muscle activity appear in the electromyography (EMG) signal. Theoretically, these bursts of activity likely occur because motor units are constrained to fire temporally close to one another and thus the impulses are “clustered” with short delays to elicit bursts of muscle activity. The purpose of this study was to investigate whether a sequence comprised of “clustered” motor unit action potentials (MUAP) can explain spectral and amplitude changes of the EMG during a simulated motor task. This question would be difficult to answer experimentally and thus, required a model to study this type of muscle activation pattern. To this end, we modeled two EMG signals, whereby a single MUAP was either convolved with a randomly distributed impulse train (EMG-rand) or a “clustered” sequence of impulses (EMG-clust). The clustering occurred in windows lasting 5–100 ms. A final mixed signal of EMG-clust and EMG-rand, with ratios (1:1–1:10), was also modeled. A ratio of 1:1 would indicate that 50% of MUAP were randomly distributed, while 50% of “clustered” MUAP occurred in a given time window (5–100 ms). The results of the model showed that clustering MUAP caused a downshift in the mean power frequency (i.e., ~30 Hz) with the largest shift occurring with a cluster window of 10 ms. The mean frequency shift was largest when the ratio of EMG-clust to EMG-rand was high. Further, the clustering of MUAP also caused a substantial increase in the amplitude of the EMG signal. This model potentially explains an activation pattern that changes the EMG spectra during a motor task and thus, a potential activation pattern of muscles observed experimentally. Changes in EMG measurements during fatiguing conditions are typically attributed to slowing of conduction velocity but could, per this model, also result from changes of the clustering of MUAP. From a clinical standpoint, this type of muscle activation

  5. Effect of Dexmedetomidine and Propofol on Basal Ganglia Activity in Parkinson Disease: A Controlled Clinical Trial.

    Science.gov (United States)

    Martinez-Simon, Antonio; Alegre, Manuel; Honorato-Cia, Cristina; Nuñez-Cordoba, Jorge M; Cacho-Asenjo, Elena; Trocóniz, Iñaki F; Carmona-Abellán, Mar; Valencia, Miguel; Guridi, Jorge

    2017-06-01

    Deep brain stimulation electrodes can record oscillatory activity from deep brain structures, known as local field potentials. The authors' objective was to evaluate and quantify the effects of dexmedetomidine (0.2 μg·kg·h) on local field potentials in patients with Parkinson disease undergoing deep brain stimulation surgery compared with control recording (primary outcome), as well as the effect of propofol at different estimated peak effect site concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 μg/ml) from control recording. A nonrandomized, nonblinded controlled clinical trial was carried out to assess the change in local field potentials activity over time in 10 patients with Parkinson disease who underwent deep brain stimulation placement surgery (18 subthalamic nuclei). The relationship was assessed between the activity in nuclei in the same patient at a given time and repeated measures from the same nucleus over time. No significant difference was observed between the relative beta power of local field potentials in dexmedetomidine and control recordings (-7.7; 95% CI, -18.9 to 7.6). By contrast, there was a significant decline of 12.7% (95% CI, -21.3 to -4.7) in the relative beta power of the local field potentials for each increment in the estimated peak propofol concentrations at the effect site relative to the control recordings. Dexmedetomidine (0.2 μg·kg·h) did not show effect on local field potentials compared with control recording. A significant deep brain activity decline from control recording was observed with incremental doses of propofol.

  6. [Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

    Science.gov (United States)

    Martínez-Múgica, Cristina

    2015-12-01

    Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

  7. Pyochelin Potentiates the Inhibitory Activity of Gallium on Pseudomonas aeruginosa

    Science.gov (United States)

    Frangipani, Emanuela; Bonchi, Carlo; Minandri, Fabrizia; Imperi, Francesco

    2014-01-01

    Gallium (Ga) is an iron mimetic that has successfully been repurposed for antibacterial chemotherapy. To improve the antibacterial potency of Ga on Pseudomonas aeruginosa, the effect of complexation with a variety of siderophores and synthetic chelators was tested. Ga complexed with the pyochelin siderophore (at a 1:2 ratio) was more efficient than Ga(NO3)3 in inhibiting P. aeruginosa growth, and its activity was dependent on increased Ga entrance into the cell through the pyochelin translocon. PMID:24957826

  8. Medicinal plants with potential anti-arthritic activity.

    Science.gov (United States)

    Choudhary, Manjusha; Kumar, Vipin; Malhotra, Hitesh; Singh, Surender

    2015-01-01

    Traditional medicinal plants are practiced worldwide for treatment of arthritis especially in developing countries where resources are meager. This review presents the plants profiles inhabiting throughout the world regarding their traditional usage by various tribes/ethnic groups for treatment of arthritis. Bibliographic investigation was carried out by analyzing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases from the last six decades. Plants/their parts/extracts/polyherbal formulations, toxicity studies for arthritis have been included in the review article. The profiles presented also include information about the scientific name, family, dose, methodology along with mechanism of action and toxicity profile. Research status of 20 potential plant species has been discussed. Further, geographical distribution of research, plants distribution according to families has been given in graphical form. 485 plant species belonging to 100 families, traditionally used in arthritis are used. Among 100 plant families, malvaceae constitute 16, leguminasae 7, fabaceae 13, euphorbiaceae 7, compositae 20, araceae 7, solanaceae 12, liliaceae 9, apocynaceae, lauraceae, and rubiaceae 10, and remaining in lesser proportion. It was observed in our study that majority of researches are carried mainly in developing countries like India, China, Korea and Nigeria. This review clearly indicates that list of medicinal plants presented in this review might be useful to researchers as well as practioners. This review can be useful for preliminary screening of potential anti-arthritis plants. Further toxicity profile given in the review can be useful for the researchers for finding the safe dose.

  9. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

    Science.gov (United States)

    Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

    2017-01-01

    Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils — neutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

  10. Potential functional and pathological side effects related to off-target pharmacological activity.

    Science.gov (United States)

    Lynch, James J; Van Vleet, Terry R; Mittelstadt, Scott W; Blomme, Eric A G

    2017-09-01

    Most pharmaceutical companies test their discovery-stage proprietary molecules in a battery of in vitro pharmacology assays to try to determine off-target interactions. During all phases of drug discovery and development, various questions arise regarding potential side effects associated with such off-target pharmacological activity. Here we present a scientific literature curation effort undertaken to determine and summarize the most likely functional and pathological outcomes associated with interactions at 70 receptors, enzymes, ion channels and transporters with established links to adverse effects. To that end, the scientific literature was reviewed using an on-line database, and the most commonly reported effects were summarized in tabular format. The resultant table should serve as a practical guide for research scientists and clinical investigators for the prediction and interpretation of adverse side effects associated with molecules interacting with components of this screening battery. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  12. Do Changes in Muscle Architecture Affect Post-Activation Potentiation?

    Directory of Open Access Journals (Sweden)

    Danielle Reardon, Jay R. Hoffman, Gerald T. Mangine, Adam J. Wells, Adam M. Gonzalez, Adam R. Jajtner, Jeremy R. Townsend, William P. McCormack, Jeffrey R. Stout, Maren S. Fragala, David H. Fukuda

    2014-09-01

    Full Text Available The purpose of this randomized, cross-over design study was to examine the effect of three different muscle potentiation protocols on acute changes in muscle architecture and vertical jump performance. Eleven experienced, resistance trained men (25.2±3.6y completed three potentiation squat protocols using moderate intensity (MI; 75%, 3 sets x 10 repetitions, high intensity (HI; 90%, 3 sets x 3 repetitions and 100% (1RM; 1 set x 1repetition of their 1RM. In addition, all participants completed a control session (CTL in which no protocol was performed. During each testing session, muscle architecture and vertical jump testing were assessed at baseline (BL, 8min post (8P and 20min post (20P workout. Ultrasound measures included cross sectional area (CSA and pennation angle (PANG of both the rectus femoris (RF and vastus lateralis (VL. Following each ultrasound measure, peak vertical jump power (PVJP and mean (MVJP power was assessed using an accelerometer. Magnitude based inferences were used to make comparisons between trials. The MI trial resulted in a likely greater increase from BL to 8P and 20P in RF-CSA and VL-CSA, while the HI trial resulted in a likely greater change from BL to 20P in both RF-CSA and VL-CSA. Meanwhile, changes in PVJP and MVJP for the MI trial was likely decreased at BL-8P and BL–20P, while the HI trial was shown to result in a likely or possible decrease compared to CTL at BL-8P and BL–20P, respectively. A likely negative relationship was observed between changes in VL-PANG and MVJP (r = -0.35; p , 0.018 at BL-8P, and between changes in PVJP and RF-CSA (r = -0.37; p , 0.014 at BL–20P. Results of this study were unable to demonstrate any potentiation response from the trials employed, however these protocols did result in acute muscle architectural changes.

  13. MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Lothe Ragnhild A

    2011-05-01

    Full Text Available Abstract Background Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy. Methods A panel of sarcoma cell lines with different TP53 and MDM2 status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined. Results Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type TP53 and amplified MDM2, or with Methotrexate in both MDM2 normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated TP53, but inhibited the effect of Methotrexate. Conclusion The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.

  14. The potential and hurdles of Targeted Alpha Therapy - Clinical trials and beyond

    Directory of Open Access Journals (Sweden)

    Jorgen eElgqvist

    2014-01-01

    Full Text Available This article presents a general discussion on what has been achieved so far and on the possible future developments of targeted alpha (α-particle therapy (TAT. Clinical applications and potential benefits of TAT are addressed as well as the drawbacks, such as the limited availability of relevant radionuclides. Alpha-particles have a particular advantage in targeted therapy because of their high potency and specificity. These features are due to their densely ionizing track structure and short path length. The most important consequence, and the major difference compared with the more widely used β–-particle emitters, is that single targeted cancer cells can be killed by self-irradiation with α-particles. Several clinical trials on TAT have been reported, completed, or are on-going: four using 213Bi, two with 211At, two with 225Ac, and one with 212Pb/212Bi. Important and conceptual proof-of-principle of the therapeutic advantages of α-particle therapy has come from clinical studies with 223Ra-dichloride therapy, showing clear benefits in castration-resistant prostate cancer, and has recently been approved by the Food and drug Administration (FDA.

  15. Hematopoietic Support Capacity of Mesenchymal Stem Cells: Biology and Clinical Potential.

    Science.gov (United States)

    Fajardo-Orduña, Guadalupe R; Mayani, Héctor; Montesinos, Juan J

    2015-11-01

    Mesenchymal stem cells (MSCs) play an important role in the physiology and homeostasis of the hematopoietic system. Because MSCs generate most of the stromal cells present in the bone marrow (BM), form part of the hematopoietic stem cell (HSC) niche, and produce various molecules regulating hematopoiesis, their hematopoiesis-supporting capacity has been demonstrated. In the last decade, BM-MSCs have been proposed to be useful in some ex vivo protocols for HSC expansion, with the aim of expanding their numbers for transplant purposes (HSC transplant, HSCT). Furthermore, application of MSCs has been proposed as an adjuvant cellular therapy for promoting rapid hematopoietic recovery in HSCT patients. Although the MSCs used in preliminary clinical trials have come from the BM, isolation of MSCs from far more accessible sources such as neonatal tissues has now been achieved, and these cells have been found to possess similar biological characteristics to those isolated from the BM. Therefore, such tissues are now considered as a potential alternative source of MSCs for clinical applications. In this review, we discuss current knowledge regarding the biological characteristics of MSCs as related to their capacity to support the formation of hematopoietic stem and progenitor cells. We also describe MSC manipulation for ex vivo HSC expansion protocols used for transplants and their clinical relevance for hematopoietic recovery in HSCT patients. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  16. Topical lotions utilized in outpatient rehabilitation clinics as a potential source of bacterial contamination.

    Science.gov (United States)

    Spratt, Henry G; Levine, David; Bage, Julie; Giles, David K; Collier, A Grace

    2018-02-26

    Soft tissue mobilization and massage requiring lotions or creams are commonly used interventions in outpatient rehabilitation clinics. For at least 50 years hand creams used in healthcare settings have been found to be contaminated by bacteria. The purpose of this study was to determine the current state of bacterial contamination of lotions used in clinics and to determine the efficacy of lotion preservatives to kill bacteria. Unopened containers of lotions were studied, along with 81 lotion containers used in 22 outpatient clinics in southeast Tennessee and northwest Georgia. Three sites on each container were sampled using sterile swabs. At a microbiology lab, bacterial growth media was inoculated and incubated. Of the 81 containers sampled, 16 supported bacterial growth (19.8%). Container threads displayed the highest contamination compared with other container locations (p < 0.01). No bacteria were found in unopened lotion containers, although when challenged with live bacterial cultures lotion preservatives did not kill bacteria tested. Enrichment cultures using lotions studied here supported the growth of several bacterial species. These findings suggest the need for standardized protocols to help reduce potential healthcare-associated infections due to use of lotions. Improved efficacy of preservatives added to lotions should be a priority.

  17. Clinical translation of MS-based, quantitative plasma proteomics: status, challenges, requirements, and potential.

    Science.gov (United States)

    Percy, Andrew J; Byrns, Simon; Pennington, Stephen R; Holmes, Daniel T; Anderson, N Leigh; Agreste, Tasha M; Duffy, Maureen A

    2016-07-01

    Aided by the advent of advanced mass spectrometry (MS)-based technologies and methodologies, quantitative proteomics has emerged as a viable technique to capture meaningful data for candidate biomarker evaluation. To aid clinical translation, these methods generally utilize a bottom-up strategy with isotopically labeled standards and a targeted form of MS measurement. This article reviews the status, challenges, requirements, and potential of translating current, MS-based methods to the clinical laboratory. The described methods are discussed and contrasted within a fit-for-purpose approach, while different resources for quality control, quantitative analysis, and data interpretation are additionally provided. Expert commentary: Although great strides have been made over the past five years in developing reliable quantitative assays for plasma protein biomarkers, it is crucial for investigators to have an understanding of the clinical validation process, a major roadblock in translational research. Continued progress in method design and validation of protein assays is necessary to ultimately achieve widespread adoption and regulatory approval.

  18. Theory of bio activity: the potential for skeletal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Hench, L.L. [Imperial College of Science. Technology and Me4dicine. Department of Materials, London (United Kingdom)

    1997-05-01

    During the twenty five years since the discovery of bone bonding to specific compositions of Na{sub 2}O--CaO-P{sub 2}O{sub 5}-SiO{sub 2} glasses [1,2], now termed bioactive glasses or Bio glass two paths of investigation have been followed (fig. 1). The goal of Path A has been to answer the intriguing question. What is the mechanisms of bonding between living matter (bone or soft tissue) and non-living matter (glasses)?. The primary objective of Path B has been to apply the concept of bioactive bonding, or bioactive fixation, to clinical use primarily to replace diseased or damaged bones or teeth. i.e. skeletal replacement. Results of the studies in Path A have led to the conclusion [3,4] that the inorganic reactions at the interface of bioactive glasses with tissue fluids. Steps 1-6 in Fig. 2. affect the cellular reactions at the interface. Steps 7-11 in Fig. 2. Two unique consequences of the synergistic inorganic-organic interactions are: (1) retardation of fibroblast proliferation [5]. and (2) enhanced bone proliferation at the interface, termed osteoproduction [6.7]. Bone proliferation is most effectively stimulated when the bioactive glass is combined, in the form of a high surface area particulate, with autogenous bone [8]. The composite allograft-autograft material leads to rapid bone formation throughout the mass rather being restricted to the periphery of the implant, as is generally the case for osteoconductive materials, such as synthetic hydroxyapatite (HA) [9]. This discovery of the use of bioactive particulate to enhance osteogenesis has led to two new paths of investigation. Path C is concerned with understanding and controlling the mitogenic (cellular profileration) character of these materials, and Path D involves optimizing their clinical application for repair of tissues, skeletal regeneration. The goals of this paper are: (1) to review breifly the results of Paths A and B, and (2) to forecast the direction of Paths C and D. (Author) 49 refs.

  19. Religious Activities and their Tourism Potential in Sukur Kingdom, Nigeria

    Directory of Open Access Journals (Sweden)

    Emeka Okonkwo

    2015-07-01

    Full Text Available Religious tourism is a form of tourism whereby people of the same faith travel individually or in groups for religious purposes. This form of tourism comprises many facets of the travel industry ranging from pilgrimages, missionary travel, leisure (fellowship, vacations, faith-based cruising, crusades, conventions and rallies, retreats, monastery visits and guest-stays, Christian and faith-based camps, to religious tourist attractions. In Sukur Kingdom, most tourists embark on religious travel for the primary purpose of sharing faith and fellowship together as they explore the various religious sites within Sukur and Adamawa State at large. Others still seek inspiration and desire to witness significant religious events while assisting others with humanitarian and spiritual needs. This paper examines the tourism potentials of religion/religious sites and belief systems in Sukur Kingdom with a view to harnessing them for sustainable tourism development. The study uses ethnographic methods to elicit information and analyze the data collected from respondents.

  20. Clinical potential of human-induced pluripotent stem cells : Perspectives of induced pluripotent stem cells.

    Science.gov (United States)

    Kumar, Dharmendra; Anand, Taruna; Kues, Wilfried A

    2017-04-01

    The recent establishment of induced pluripotent stem (iPS) cells promises the development of autologous cell therapies for degenerative diseases, without the ethical concerns associated with human embryonic stem (ES) cells. Initially, iPS cells were generated by retroviral transduction of somatic cells with core reprogramming genes. To avoid potential genotoxic effects associated with retroviral transfection, more recently, alternative non-viral gene transfer approaches were developed. Before a potential clinical application of iPS cell-derived therapies can be planned, it must be ensured that the reprogramming to pluripotency is not associated with genome mutagenesis or epigenetic aberrations. This may include direct effects of the reprogramming method or "off-target" effects associated with the reprogramming or the culture conditions. Thus, a rigorous safety testing of iPS or iPS-derived cells is imperative, including long-term studies in model animals. This will include not only rodents but also larger mammalian model species to allow for assessing long-term stability of the transplanted cells, functional integration into the host tissue, and freedom from undifferentiated iPS cells. Determination of the necessary cell dose is also critical; it is assumed that a minimum of 1 billion transplantable cells is required to achieve a therapeutic effect. This will request medium to long-term in vitro cultivation and dozens of cell divisions, bearing the risk of accumulating replication errors. Here, we review the clinical potential of human iPS cells and evaluate which are the most suitable approaches to overcome or minimize risks associated with the application of iPS cell-derived cell therapies.

  1. [Activated protein C resistance and factor V Leiden: clinical interest].

    Science.gov (United States)

    Guermazi, S; Znazen, R

    2011-10-01

    Activated protein C resistance (APCR) is a coagulation abnormality often linked to FV Leiden mutation, a single nucleotide G1691A substitution resulting in arginine 506→glutamine missense factor V mutation. FV Leiden has a frequency of 20 to 30% in groups of patients with venous thrombosis while it is of 4 to 10% in normal subjects. FV Leiden is considered as a weak risk factor of thrombosis except in homozygote. FV Leiden is implicated in deep venous thrombosis occurrence. Duration of oral anticoagulant treatment is six months in patients developing a first venous thrombosis except in patients with combined defects or a clinical context suggesting a high risk of severe relapse. Detection of APCR by coagulation methods is often used in first intention with a high specificity if plasmas tested are diluted in factor V deficient plasma. Genotyping study is essential to establish the heterozygote or homozygote statute and certain teams perform it directly. Nevertheless, APCR not related to FV Leiden could be an independent thrombosis risk factor. APCR and FV Leiden are included in laboratory investigations of thrombophilic markers in patients less than 50 years with venous thrombosis. In arterial thrombosis, FV Leiden implication is weak or absent. FV Leiden increases the risk of thrombosis in other situations as in patients with cancer. An association with recurrent miscarriages and other vasculoplacental complications is also reported in many studies but the data concerning the efficacy of antithrombotic treatment to prevent recurrence are currently insufficient. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  2. Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells.

    Science.gov (United States)

    Lo Re, Oriana; Panebianco, Concetta; Porto, Stefania; Cervi, Carlo; Rappa, Francesca; Di Biase, Stefano; Caraglia, Michele; Pazienza, Valerio; Vinciguerra, Manlio

    2018-02-01

    Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use. © 2017 Wiley Periodicals, Inc.

  3. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Goozee, K G; Shah, T M; Sohrabi, H R; Rainey-Smith, S R; Brown, B; Verdile, G; Martins, R N

    2016-02-14

    Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

  4. Clinical potential and challenges of using genetically modified cells for articular cartilage repair

    Science.gov (United States)

    Madry, Henning; Cucchiarini, Magali

    2011-01-01

    Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration. PMID:21674822

  5. Potential hypoglycaemic activity phenolic glycosides from Moringa oleifera seeds.

    Science.gov (United States)

    Wang, Fang; Zhong, Huan-Huan; Chen, Wei-Ke; Liu, Qing-Pu; Li, Cun-Yu; Zheng, Yun-Feng; Peng, Guo-Ping

    2017-08-01

    Moringa oleifera seed has remarkable curative effects on reducing blood pressure, blood sugar and enhancing human immunity. In this study, one novel phenolic glycoside (1) together with four known compounds 2-5 were isolated from the macroporous resin adsorption extract of M. oleifera seeds, and the compound 3 was reported for the first time from this plant. The structure of the new crystalline compound was determined on the basis of spectroscopic analyses including mass spectrometry, 1D and 2D NMR experiments. The hypoglycaemic activity of isolated compounds was investigated with HepG2 cell and STZ-induced mice. It was found that compound 1, 4 and 5 could promote the glucose consumption of insulin resistance cells and reduce blood glucose levels of STZ-induced mice. This study concludes that compound 1, 4 and 5 may be developed as new and safe hypoglycaemic drugs.

  6. Synthesis of geranylhydroquinone derivatives with potential cytotoxic activity

    Energy Technology Data Exchange (ETDEWEB)

    Baeza, Evelyn; Catalan, Karen; Pena-Cortes, Hugo; Espinoza, Luis, E-mail: luis.espinozac@usm.cl [Departamento de Quimica, Universidad Tecnica Federico Santa Maria, Valparaiso (Chile); Villena, Joan [Facultad de Medicina, Universidad de Valparaiso, Centro Regional de Estudios en Alimentos Saludables, Valparaiso (Chile); Carrasco, Hector [Departamento de Ciencias Quimicas, Universidad Andres Bello, Campus Vina del Mar (Chile)

    2012-07-01

    Natural geranylhydroquinone 1 and geranyl-p-methoxyphenol 2 were prepared by Electrophilic Aromatic Substitution (EAS) reactions between geraniol and 1,4-hydroquinone or p-methoxyphenol respectively, using BF{sub 3} {center_dot}Et{sub 2}O as a catalyst. Furthermore, natural geranylquinone 3, geranyl-1,4-dimethoxyquinone 4 and the new geranyl-4-methoxyphenyl acetate 5 were obtained by chemical transformations of 1 and 2. The compounds were evaluated for their in vitro cytotoxicity activities against cultured human cancer cells of PC-3 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma, and Dermal Human ibroblasts DHF. IC{sub 50} values were in the {mu}M range. (author)

  7. Pollution effects on fisheries — potential management activities

    Science.gov (United States)

    Sindermann, C. J.

    1980-03-01

    Management of ocean pollution must be based on the best available scientific information, with adequate consideration of economic, social, and political realities. Unfortunately, the best available scientific information about pollution effects on fisheries is often fragmentary, and often conjectural; therefore a primary concern of management should be a critical review and assessment of available factual information about effects of pollutants on fish and shellfish stocks. A major problem in any such review and assessment is the separation of pollutant effects from the effects of all the other environmental factors that influence survival and well-being of marine animals. Data from long-term monitoring of resource abundance, and from monitoring of all determinant environmental variables, will be required for analyses that lead to resolution of the problem. Information must also be acquired about fluxes of contaminants through resource-related ecosystems, and about contaminant effects on resource species as demonstrated in field and laboratory experiments. Other possible management activities include: (1) encouragement of continued efforts to document clearly the localized and general effects of pollution on living resources; (2) continued pressure to identify and use reliable biological indicators of environmental degradation (indicators of choice at present are: unusually high levels of genetic and other anomalies in the earliest life history stages; presence of pollution-associated disease signs, particularly fin erosion and ulcers, in fish; and biochemical/physiological changes); and (3) major efforts to reduce inputs of pollutants clearly demonstrated to be harmful to living resources, from point sources as well as ocean dumping. Such pollution management activities, based on continuous efforts in stock assessment, environmental assessment, and experimental studies, can help to insure that rational decisions will be made about uses and abuses of coastal

  8. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  9. In vitro anti-tuberculosis activity of azole drugs against Mycobacterium tuberculosis clinical isolates.

    Science.gov (United States)

    Imperiale, Belén R; Cataldi, Ángel A; Morcillo, Nora S

    Latent tuberculosis has been associated with the persistence of dormant Mycobacterium tuberculosis in the organism of infected individuals, who are reservoirs of the bacilli and the source for spreading the disease in the community. New active anti-TB drugs exerting their metabolic action at different stages and on latent/dormant bacilli are urgently required to avoid endogenous reactivations and to be part of treatments of multi- and extensively-drug resistant tuberculosis (M/XDR-TB). It was previously reported that azole drugs are active against M. tuberculosis. For that reason, the aims of this study were to determine the in vitro activity of azole drugs, imidazole (clotrimazole, CLO and econazole, ECO) and nitroimidazole (metronidazole, MZ and ipronidazole, IPZ), against a collection of MDR M. tuberculosis clinical isolates; and to analyze their potential use in both the LTB and the active forms of M/XDR-TB treatments. A total of 55 MDR M. tuberculosis isolates and H37Rv were included. MZ and IPZ activity against M. tuberculosis isolates were tested using anaerobic culture conditions. The activity of ECO and CLO was measured by the minimal inhibitory concentration (MIC) using a microdilution colorimetric method. MZ and IPZ showed bacteriostatic activity against M. tuberculosis strains. MIC 50 and MIC 90 to ECO was 4.0μg/ml, while MIC 50 to CLO was 4.0μg/ml and MIC 90 was 8.0μg/ml respectively. All azole compounds tested in the study showed inhibitory activity against MDR M. tuberculosis clinical isolates. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Motor Imagery-Based Rehabilitation: Potential Neural Correlates and Clinical Application for Functional Recovery of Motor Deficits after Stroke.

    Science.gov (United States)

    Tong, Yanna; Pendy, John T; Li, William A; Du, Huishan; Zhang, Tong; Geng, Xiaokun; Ding, Yuchuan

    2017-05-01

    Motor imagery (MI), defined as the mental implementation of an action in the absence of movement or muscle activation, is a rehabilitation technique that offers a means to replace or restore lost motor function in stroke patients when used in conjunction with conventional physiotherapy procedures. This article briefly reviews the concepts and neural correlates of MI in order to promote improved understanding, as well as to enhance the clinical utility of MI-based rehabilitation regimens. We specifically highlight the role of the cerebellum and basal ganglia, premotor, supplementary motor, and prefrontal areas, primary motor cortex, and parietal cortex. Additionally, we examine the recent literature related to MI and its potential as a therapeutic technique in both upper and lower limb stroke rehabilitation.

  11. Exercise and physical activity in mental disorders: clinical and experimental evidence.

    Science.gov (United States)

    Zschucke, Elisabeth; Gaudlitz, Katharina; Ströhle, Andreas

    2013-01-01

    Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.

  12. Potential clinical applications of adult human mesenchymal stem cell (Prochymal® therapy

    Directory of Open Access Journals (Sweden)

    Patel AN

    2011-11-01

    Full Text Available Amit N Patel, Jorge GenoveseUniversity of Utah School of Medicine, Salt Lake City, UT, USAAbstract: In vitro, in vivo animal, and human clinical data show a broad field of application for mesenchymal stem cells (MSCs. There is overwhelming evidence of the usefulness of MSCs in regenerative medicine, tissue engineering, and immune therapy. At present, there are a significant number of clinical trials exploring the use of MSCs for the treatment of various diseases, including myocardial infarction and stroke, in which oxygen suppression causes widespread cell death, and others with clear involvement of the immune system, such as graft-versus-host disease, Crohn's disease, and diabetes. With no less impact, MSCs have been used as cell therapy to treat defects in bone and cartilage and to help in wound healing, or in combination with biomaterials in tissue engineering development. Among the MSCs, allogeneic MSCs have been associated with a regenerative capacity due to their unique immune modulatory properties. Their immunosuppressive capability without evidence of immunosuppressive toxicity at a global level define their application in the treatment of diseases with a pathogenesis involving uncontrolled activity of the immune system. Until now, the limitation in the number of totally characterized autologous MSCs available represents a major obstacle to their use for adult stem cell therapy. The use of premanufactured allogeneic MSCs from controlled donors under optimal conditions and their application in highly standardized clinical trials would lead to a better understanding of their real applications and reduce the time to clinical translation.Keywords: regeneration, immunomodulation, tissue engineering, allogeneic, mesenchymal stem cells

  13. Clinical PET activities in European and Asia-Oceanian Countries

    International Nuclear Information System (INIS)

    Tashiro, Manabu; Ito, Masatoshi; Yamaguchi, Keiichiro; Kubota, Kazuo; Fujimoto, Toshihiko; Sasaki, Hidetada; Moser, E.

    2001-01-01

    Clinical diagnosis using positron emission tomography (PET) requires high costs. Therefore, sociomedical evaluation is very important for spread of clinical PET. In this report, sociomedical situation in European and Asia-Oceanian countries, especially concerning transportation of 18 F-FDG and reimbursement of medical costs for clinical PET indications, is reported. It seems that UK, Germany and Belgium are the most advanced in clinical PET in Europe. In these countries, many PET investigations are reimbursed though systems are different among the countries. In UK, both public and private insurance gives authorization for clinical PET to some extent. In Germany, private health insurance companies give authorization but public insurance has not. In Belgium, private health insurance does not exist and public insurance gives authorization for clinical PET. Other European countries seem to be in transitional stages. Transportation of 18 F-FDG has been already started in almost every country in Europe and Asia-Oceania. In Japan, neither transportation of FDG nor full reimbursement of clinical PET has not started yet and this situation seems to be exceptional. To promote clinical PET in Japan, there is the need of at least establishing a list of clinical indications for PET investigations and establishing commercial-based 18 F-FDG supplying system. They could be regarded as a kind of infrastructure for spread of clinical PET. (author)

  14. [Evaluation of the concordance between biological markers and clinical activity in inflammatory bowel disease].

    Science.gov (United States)

    Miranda García, Pablo; Chaparro, María; Gisbert, Javier P

    2015-01-06

    Endoscopy is the gold standard to assess disease severity in inflammatory bowel disease, although it is an invasive procedure. Clinical activity and biological markers have been routinely used to determine disease activity in a non-invasive manner. The aim of this study was to determine concordance between common biological markers (C reactive protein, orosomucoid, erythrocyte sedimentation rate, fibrinogen, platelets, leukocytes, neutrophils and haemoglobin) and clinical activity in inflammatory bowel disease. Consecutive patients with inflammatory bowel disease were included. Clinical activity was evaluated according to the Harvey-Bradshaw index in Crohn's disease and to the partial Mayo score in ulcerative colitis. Serum concentrations of the different biomarkers were analysed. Concordance between clinical activity and elevation of the serological biomarkers was determined using the kappa statistic. In total, 350 patients were included (median age 46 years, Crohn's disease 59%). Eleven percent of patients had clinical activity. Crohn's disease patients had mild clinical activity in 44% of cases, moderate disease in 44% and only 12% of patients had severe clinical activity. In ulcerative colitis, patients had mild, moderate and severe clinical activity in 50, 42 and 8% of cases, respectively. None of the biomarkers included had an acceptable concordance with clinical activity (kappa statistic ≤ 0.30). Concordance between serological biomarkers and clinical activity in inflammatory bowel disease is remarkably low. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  15. Antibacterial activity of Artemisia nilagirica leaf extracts against clinical and phytopathogenic bacteria

    Science.gov (United States)

    2010-01-01

    Background The six organic solvent extracts of Artemisia nilagirica were screened for the potential antimicrobial activity against phytopathogens and clinically important standard reference bacterial strains. Methods The agar disk diffusion method was used to study the antibacterial activity of A. nilagirica extracts against 15 bacterial strains. The Minimum Inhibitory Concentration (MIC) of the plant extracts were tested using two fold agar dilution method at concentrations ranging from 32 to 512 μg/ml. The phytochemical screening of extracts was carried out for major phytochemical derivatives in A. nilagirica. Results All the extracts showed inhibitory activity for gram-positive and gram-negative bacteria except for Klebsiella pneumoniae, Enterococcus faecalis and Staphylococcus aureus. The hexane extract was found to be effective against all phytopathogens with low MIC of 32 μg/ml and the methanol extract exhibited a higher inhibition activity against Escherichia coli, Yersinia enterocolitica, Salmonella typhi, Enterobacter aerogenes, Proteus vulgaris, Pseudomonas aeruginosa (32 μg/ml), Bacillus subtilis (64 μg/ml) and Shigella flaxneri (128 μg/ml). The phytochemical screening of extracts answered for the major derivative of alkaloids, amino acids, flavonoids, phenol, quinines, tannins and terpenoids. Conclusion All the extracts showed antibacterial activity against the tested strains. Of all, methanol and hexane extracts showed high inhibition against clinical and phytopathogens, respectively. The results also indicate the presence of major phytochemical derivatives in the A. nilagirica extracts. Hence, the isolation and purification of therapeutic potential compounds from A. nilagirica could be used as an effective source against bacterial diseases in human and plants. PMID:20109237

  16. Antibacterial activity of Artemisia nilagirica leaf extracts against clinical and phytopathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Hopper Waheeta

    2010-01-01

    Full Text Available Abstract Background The six organic solvent extracts of Artemisia nilagirica were screened for the potential antimicrobial activity against phytopathogens and clinically important standard reference bacterial strains. Methods The agar disk diffusion method was used to study the antibacterial activity of A. nilagirica extracts against 15 bacterial strains. The Minimum Inhibitory Concentration (MIC of the plant extracts were tested using two fold agar dilution method at concentrations ranging from 32 to 512 μg/ml. The phytochemical screening of extracts was carried out for major phytochemical derivatives in A. nilagirica. Results All the extracts showed inhibitory activity for gram-positive and gram-negative bacteria except for Klebsiella pneumoniae, Enterococcus faecalis and Staphylococcus aureus. The hexane extract was found to be effective against all phytopathogens with low MIC of 32 μg/ml and the methanol extract exhibited a higher inhibition activity against Escherichia coli, Yersinia enterocolitica, Salmonella typhi, Enterobacter aerogenes, Proteus vulgaris, Pseudomonas aeruginosa (32 μg/ml, Bacillus subtilis (64 μg/ml and Shigella flaxneri (128 μg/ml. The phytochemical screening of extracts answered for the major derivative of alkaloids, amino acids, flavonoids, phenol, quinines, tannins and terpenoids. Conclusion All the extracts showed antibacterial activity against the tested strains. Of all, methanol and hexane extracts showed high inhibition against clinical and phytopathogens, respectively. The results also indicate the presence of major phytochemical derivatives in the A. nilagirica extracts. Hence, the isolation and purification of therapeutic potential compounds from A. nilagirica could be used as an effective source against bacterial diseases in human and plants.

  17. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    Science.gov (United States)

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  18. Miscellaneous conditions of the shoulder: Anatomical, clinical, and pictorial review emphasizing potential pitfalls in imaging diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Farid, Nikdokht [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); Bruce, Dean [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); University of Alberta, Edmonton, Alberta (Canada); Chung, Christine B. [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States)], E-mail: cbchung@ucsd.edu

    2008-10-15

    The purpose of this article is to review the key imaging findings in major categories of pathology affecting the shoulder joint including hydroxyapatite deposition disease, rotator cuff interval pathology, acromioclavicular joint pathology, glenohumeral osteoarthrosis, and synovial inflammatory processes, with specific emphasis on findings that have associated pitfalls in imaging diagnosis. The pathophysiology and clinical manifestations of the above mentioned categories of pathology will be reviewed, followed in each section by a detailed pictorial review of the key imaging findings in each category including plain film, computed tomography, and magnetic resonance imaging findings as applicable. Imaging challenges that relate to both diagnosis and characterization will be addressed with each type of pathology. The goal is that after reading this article, the reader will be able to recognize the key imaging findings in major categories of pathology affecting the shoulder joint and will become familiar with the potential pitfalls in their imaging diagnosis.

  19. Qualitative analysis of the impact of Oral Potentially Malignant Disorders on daily life activities.

    Directory of Open Access Journals (Sweden)

    Jyothi Tadakamadla

    Full Text Available To evaluate the impact of Oral Potentially Malignant Disorders (OPMD on daily life activities.Patients diagnosed with Oral Leukoplakia, Oral submucous fibrosis and Oral Lichen Planus attending the Oral Medicine clinic of Panineeya Institute of Dental Sciences & Research Centre, Hyderabad, India were invited to participate. Eighteen interviews and three focus groups were conducted in a non-clinical setting. Voice recordings were transcribed and translated from Telugu to English. Data coding was performed using the NVivo software.Sample size for this qualitative study comprised 32 patients. Four main themes emerged: (1 difficulties with diagnosis and knowledge about the condition, (2 physical impairment and functional limitations, (3 psychological and social wellbeing and (4 effects of treatment on daily life. In a majority of the patients, most of the interview time was spent discussing physical impairment and functional limitations. Patients also reported their mouth condition having a debilitating effect on their psychological well-being and social interactions.'Physical impairment and functional limitations' was the most important theme for many of the patients. However, the impacts of OPMD also extended beyond physical impairment and functional limitations to aspects of daily living, notably psychological and social wellbeing.

  20. Browser based platform in maintaining clinical activities – use of the iPads in head and neck clinics

    International Nuclear Information System (INIS)

    Yang, W Y; Moore, J; Quon, H; Evans, K; Sharabi, A; Herman, J; Hacker-Prietz, A; McNutt, T

    2014-01-01

    Purpose: Incompatibility between documentation and clinical workflow causes physician resistance in organized data collection, which in turn complicates the use of data in patient care improvement. To resolve the gap, we developed an iPad compatible in situ browser-based platform that integrates clinical activity with data collection and analysis presentation. The ability to perform in-clinic activities and monitor decision making using the iPad was evaluated. Methods: A browser-based platform that can exchange and present analysed data from the MOSAIQ database was developed in situ, the iPads were distributed in head and neck clinics to present the browser for clinical activities, data collection and assessment monitoring. Performance of the iPads for in-clinic activities was observed. Results: All in-clinic documentation activities can be performed without workstation computers. Accessing patient record and previous assessments was significantly faster without having to open the MOSAIQ application. Patient assessments can be completed with the physician facing the patient. Graphical presentation of toxicity progression and patient radiation plans to the patient can be performed in single interface without patient leaving the seating area. Updates in patient treatment status and medical history were presented in real time without having to move paper charts around. Conclusions: The iPad can be used in clinical activities independent of computer workstations. Improvements in clinical workflow can be critical in reducing physician resistance in data maintenance. Using the iPad in providing real-time quality monitoring is intuitive to both providers and patients.

  1. Browser Based Platform in Maintaining Clinical Activities - Use of The iPads in Head and Neck Clinics

    Science.gov (United States)

    Yang, W. Y.; Moore, J.; Quon, H.; Evans, K.; Sharabi, A.; Herman, J.; Hacker-Prietz, A.; McNutt, T.

    2014-03-01

    Purpose: Incompatibility between documentation and clinical workflow causes physician resistance in organized data collection, which in turn complicates the use of data in patient care improvement. To resolve the gap, we developed an iPad compatible in situ browser-based platform that integrates clinical activity with data collection and analysis presentation. The ability to perform in-clinic activities and monitor decision making using the iPad was evaluated. Methods: A browser-based platform that can exchange and present analysed data from the MOSAIQ database was developed in situ, the iPads were distributed in head and neck clinics to present the browser for clinical activities, data collection and assessment monitoring. Performance of the iPads for in-clinic activities was observed. Results: All in-clinic documentation activities can be performed without workstation computers. Accessing patient record and previous assessments was significantly faster without having to open the MOSAIQ application. Patient assessments can be completed with the physician facing the patient. Graphical presentation of toxicity progression and patient radiation plans to the patient can be performed in single interface without patient leaving the seating area. Updates in patient treatment status and medical history were presented in real time without having to move paper charts around. Conclusions: The iPad can be used in clinical activities independent of computer workstations. Improvements in clinical workflow can be critical in reducing physician resistance in data maintenance. Using the iPad in providing real-time quality monitoring is intuitive to both providers and patients.

  2. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change.

    Science.gov (United States)

    Riva, Giuseppe; Baños, Rosa M; Botella, Cristina; Mantovani, Fabrizia; Gaggioli, Andrea

    2016-01-01

    During life, many personal changes occur. These include changing house, school, work, and even friends and partners. However, the daily experience shows clearly that, in some situations, subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: (a) the focus of personal change is reducing the distance between self and reality (conflict); (b) this reduction is achieved through (1) an intense focus on the particular experience creating the conflict or (2) an internal or external reorganization of this experience; (c) personal change requires a progression through a series of different stages that however happen in discontinuous and non-linear ways; and (d) clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper focuses on the two leading virtual technologies - augmented reality (AR) and virtual reality (VR) - exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience by focusing on the high level of personal efficacy and self-reflectiveness generated by their sense of presence and emotional engagement. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering, and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual's worldview.

  3. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change

    Science.gov (United States)

    Riva, Giuseppe; Baños, Rosa M.; Botella, Cristina; Mantovani, Fabrizia; Gaggioli, Andrea

    2016-01-01

    During life, many personal changes occur. These include changing house, school, work, and even friends and partners. However, the daily experience shows clearly that, in some situations, subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: (a) the focus of personal change is reducing the distance between self and reality (conflict); (b) this reduction is achieved through (1) an intense focus on the particular experience creating the conflict or (2) an internal or external reorganization of this experience; (c) personal change requires a progression through a series of different stages that however happen in discontinuous and non-linear ways; and (d) clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper focuses on the two leading virtual technologies – augmented reality (AR) and virtual reality (VR) – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience by focusing on the high level of personal efficacy and self-reflectiveness generated by their sense of presence and emotional engagement. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering, and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual’s worldview. PMID:27746747

  4. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change

    Directory of Open Access Journals (Sweden)

    Giuseppe Riva

    2016-09-01

    Full Text Available During our life we undergo many personal changes: we change our house, our school, our work and even our friends and partners. However, our daily experience shows clearly that in some situations subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: a the focus of personal change is reducing the distance between self and reality (conflict; b this reduction is achieved through (1 an intense focus on the particular experience creating the conflict or (2 an internal or external reorganization of this experience; c personal change requires a progression through a series of different stages; d clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper will focus on the two leading virtual technologies – Augmented Reality (AR and Virtual Reality (VR – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience, by focusing on the high level of self-reflectiveness and personal efficacy induced by their emotional engagement and sense of presence. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual’s worldview.

  5. Activation of dimeric glucocorticoid receptors in osteoclast progenitors potentiates RANKL induced mature osteoclast bone resorbing activity.

    Science.gov (United States)

    Conaway, H Herschel; Henning, Petra; Lie, Anita; Tuckermann, Jan; Lerner, Ulf H

    2016-12-01

    Glucocorticoid (GC) therapy is the greatest risk factor for secondary osteoporosis. Pathogenic mechanisms involve an initial increase in bone resorption followed by decreased bone formation. To gain a better understanding of the resorptive activity of GCs, we have used mouse bone marrow macrophages (BMM) to determine if GCs can directly modulate RANKL stimulated osteoclast formation and/or activity. In agreement with previous studies, experiments performed in plastic wells showed that GCs (dexamethasone, hydrocortisone, and prednisolone) inhibited osteoclast number and size during the initial phases of RANKL stimulated osteoclastogenesis; however, in prolonged cultures, decreased apoptosis was observed and escape from GC induced inhibition occurred with an enhanced number of osteoclasts formed, many with an increased area. When BMM cells were seeded on bone slices, GCs robustly enhanced RANKL stimulated formation of resorption pits and release of CTX without affecting the number or size of osteoclasts formed and with no effect on apoptosis. Stimulation of pit formation was not associated with increased life span of osteoclasts or an effect on mRNA expression of several osteoclastic or osteoclastogenic genes. The potentiation of RANKL induced CTX release by dexamethasone was significantly less in BMM cells from mice with conditional knockout of the osteoclastic glucocorticoid receptor and completely absent in cells from GR dim mice, which carry a point mutation in one dimerizing interface of the GC receptor. These data suggest that: 1. Plastic is a poor medium to use for studying direct effects of GCs on osteoclasts 2. GCs can enhance bone resorption without decreasing apoptosis, and 3. A direct enhancement of RANKL mediated resorption is stimulated by the dimeric GC-receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Etanercept-induced injection site reactions: potential pathomechanisms and clinical assessment.

    Science.gov (United States)

    Batycka-Baran, Aleksandra; Flaig, Michael; Molin, Sonja; Ruzicka, Thomas; Prinz, Joerg C

    2012-11-01

    Etanercept (ETN) is a tumor necrosis factor alpha (TNF-α) antagonist used for the treatment of chronic inflammatory disorders. Injection site reactions (ISRs) are reported to be the most common adverse event of ETN therapy. While their mechanisms are not completely understood, the occurrence of ETN-ISRs could indicate a risk of systemic immune-mediated severe adverse drug reactions. Based on two cases and a review of the literature, the characteristics and frequency of ETN-ISRs were assessed. This article discusses their potential mechanisms and clinical relevance, and provides recommendations for the management of patients presenting with ETN-ISRs. Basically, irritative and immune-mediated ISRs may be distinguished. The formation of anti-drug antibodies (ADAs) may promote immune-mediated ISRs that likely represent either anaphylactic type I reactions, or cutaneous Arthus-like type III reactions according to the Coombs and Gell classification. A differentiation between these reactions by clinical course and etanercept-skin testing may help to decide if ETN treatment should be stopped to avoid the development of more severe adverse drug reactions if ISRs occur.

  7. Diffusion tensor imaging for Alzheimer's disease: A review of concepts and potential clinical applicability

    Directory of Open Access Journals (Sweden)

    Luciano de Gois Vasconcelos

    Full Text Available Abstract In view of the urgent need to identify an early and specific biomarker for Alzheimer's disease (AD, a PubMed database search was performed using the terms "Alzheimer disease" and "Diffusion Magnetic Resonance Imaging" to enable review of Diffusion tensor imaging (DTI concepts and its potential clinical role in AD evaluation. Detailed analysis of selected abstracts showed that the main DTI measures, fractional anisotropy and apparent diffusion coefficient, indicators of fiber tract integrity, provide a direct assessment of WM fibers and may be used as a new biomarker for AD. These findings were found to correlate with cognitive assessments, rates of AD progression and were also able to differentiate among groups including mild cognitive impairment, AD, and other dementias. Despite several consistent DTI findings in AD patients, there is still a lack of knowledge and studies on the DTI field. DTI is not yet ready for clinical use, and requires extensive further research in order to achieve this goal.

  8. Clinical magnetic resonance spectroscopy: Potentials and methods for whole-body scanners

    International Nuclear Information System (INIS)

    Wicklow, K.; Kolem, H.; Schneider, M.; Sauter, R.

    1993-01-01

    MR Spectroscopy offers the unique possibility of monitoring the metabolism of various organs non-invasively. Using examples of 1 H and 31 P MR spectra, experimental and comercially available techniques are presented and evaluated with regard to their potential clinical application. An example of a 1 H human brain spectrum with a pathological lactate level illustrates the requirements for MRS examinations in terms of spatial and spectral resolution. STEAM, Spin-Echo, and Chemical Shift Resolved Imaging (CSI) techniques for 1 H MRS are compared. In the field of 31 P MRS, typical CSI spectra of the brain and liver are presented. First experimental results with a new double-oblique 3D-CSI technique for measurement of PCr/ATP ratios of different anatomical regions of the human heart are shown. The advantages of using double-resonance techniques for Nuclear Overhauser Enhancement (NOE) and decoupling are shown by the example of the phosphodiesters of the liver. The energy metabolism of skeletal muscle under exercise is resolved with 5 sec/spectrum, showing breakdown and synthesis of photocreatine (PCr) and inorganic phosphate (Pi). Appropriate instrumentation and technique are available to many clinics today; great interest now is directed towards the diagnostic value of MRS for certain indications. (orig.) [de

  9. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma.

    Science.gov (United States)

    Wu, Chun-Chieh; Lin, Zu-Yau; Kuoc, Chao-Hung; Chuang, Wan-Long

    2015-05-01

    Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH) were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment). Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167). The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015). In addition to the well-known direct colchicine-tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience. Copyright © 2015. Published by Elsevier Taiwan.

  10. Bio-scaffolds in organ-regeneration: Clinical potential and current challenges.

    Science.gov (United States)

    Yesmin, S; Paget, M B; Murray, H E; Downing, R

    2017-09-01

    Cadaveric organ transplantation represents the definitive treatment option for end-stage disease but is restricted by the shortage of clinically-viable donor organs. This limitation has, in part, driven current research efforts for in vitro generation of transplantable tissue surrogates. Recent advances in organ reconstruction have been facilitated by the re-purposing of decellularized whole organs to serve as three-dimensional bio-scaffolds. Notably, studies in rodents indicate that such scaffolds retain native extracellular matrix components that provide appropriate biochemical, mechanical and physical stimuli for successful tissue/organ reconstruction. As such, they support the migration, adhesion and differentiation of reseeded primary and/or pluripotent cell populations, which mature and achieve functionality through short-term conditioning within specialized tissue bioreactors. Whilst these findings are encouraging, significant challenges remain to up-scale the present technology to accommodate human-sized organs and thereby further the translation of this approach towards clinical use. Of note, the diverse structural and cellular composition of large mammalian organ systems mean that a "one-size fits all" approach cannot be adopted either to the methods used for their decellularization or the cells required for subsequent re-population, to create fully functional entities. The present review seeks to highlight the clinical potential of decellularized organ bio-scaffolds as a route to further advance the field of tissue- and organ-regeneration, and to discuss the challenges which are yet to be addressed if such a technology is ever to become a credible rival to conventional organ allo-transplantation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Potential facilitators and barriers to adopting standard treatment guidelines in clinical practice.

    Science.gov (United States)

    Sharma, Sangeeta; Pandit, Ajay; Tabassum, Fauzia

    2017-04-18

    Purpose The purpose of this paper is to assess medicines information sources accessed by clinicians, if sources differed in theory and practice and to find out the barriers and facilitators to effective guideline adoption. Design/methodology/approach In all, 183 doctors were surveyed. Barriers and facilitators were classified as: communication; potential adopters; innovation; organization characteristics and environmental/social/economic context. Findings Most of the clinicians accessed multiple information sources including standard treatment guidelines, but also consulted seniors/colleagues in practice. The top three factors influencing clinical practice guideline adoption were innovation characteristics, environmental context and individual characteristics. The respondents differed in the following areas: concerns about flexibility offered by the guideline; denying patients' individuality; professional autonomy; insights into gaps in current practice and evidence-based practice; changing practices with little or no benefit. Barriers included negative staff attitudes/beliefs, guideline integration into organizational structures/processes, time/resource constraints. Fearing third parties (government and insurance companies) restricting medicines reimbursement and poor liability protection offered by the guidelines emerged as the barriers. Facilitators include aligning organizational structures/processes with the innovation; providing leadership support to guide diffusion; increasing awareness and enabling early innovation during pre/in-service training, with regular feedback on outcomes and use. Practical implications Guideline adoption in clinical practice is partly within doctors' control. There are other key prevailing factors in the local context such as environmental, social context, professional and organizational culture affecting its adoption. Organizational policy and accreditation standards necessitating adherence can serve as a driver. Originality

  12. Evaluating acute effects of potential reduced-exposure products for smokers: clinical laboratory methodology.

    Science.gov (United States)

    Breland, Alison B; Buchhalter, August R; Evans, Sarah E; Eissenberg, Thomas

    2002-01-01

    Harm reduction for tobacco smokers may involve reducing their exposure to lethal smoke constituents. Assessing smoke constituent exposure and any resulting harm reduction from a potential reduced-exposure product (PREP) will involve preclinical, clinical, and epidemiological research. The purpose of this study was to evaluate a clinical laboratory model for assessing the acute effects of PREPs for smokers. Philip Morris' Accord and R.J. Reynolds' Eclipse were used as examples. Twenty overnight-abstinent smokers (> 15 'light' or 'ultra-light' cigarettes/day) participated in 4 Latin-square ordered, 2.5-hr sessions in which they completed an 8-puff smoking bout every 30 minutes. Sessions were separated by at least 24 hours and differed by product used: own brand, denicotinized tobacco cigarettes, Accord, or Eclipse. Tobacco withdrawal and carbon monoxide (CO) were assessed before and after smoking, heart rate was assessed before and during smoking, and puff volume, duration, and interpuff interval were assessed while subjects smoked. Blood was sampled at the beginning and end of each session. Relative to normal cigarettes, Accord was less effective at suppressing withdrawal and produced minimal CO boost despite the fact that, when using Accord, subjects took bigger and longer puffs. Eclipse suppressed withdrawal fully and increased CO boost by approximately 30%. Own brand, Accord, and Eclipse, but not denicotinized cigarettes, increased plasma nicotine concentration. Taken together, these results suggest that neither Accord nor Eclipse is likely to be an effective reduced-exposure product for smokers and that this clinical laboratory model is valuable.

  13. Potential sources of reinforcement and punishment in a drug-free treatment clinic: client and staff perceptions.

    Science.gov (United States)

    Roll, John M; Chudzynski, Joy E; Richardson, Gina

    2005-01-01

    Contingency management interventions are quite successful at initiating abstinence from drugs of abuse. However, these approaches to drug abuse treatment are often criticized because of their perceived cost. One way to reduce the cost of contingency management interventions would be to use nonmonetary sources of reinforcement or punishment. A number of reports have discussed the availability of potential sources of reinforcement in opiate replacement clinics. This report describes the availability of potential sources of reinforcement and punishment available in drug-free treatment programs. Both clients and clinic staff rated a number of items in terms of their potential reinforcing and punishing efficacy. Results suggest that there are several sources of reinforcement and punishment available in drug-free clinics, which could be used in contingency management programs. The results also suggest that the clinic staff perceives potential sources of punishment as more aversive than do the clients.

  14. The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

    Science.gov (United States)

    Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

    2017-05-01

    To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

  15. Chemical analysis, inhibition of biofilm formation and biofilm eradication potential of Euphorbia hirta L. against clinical isolates and standard strains.

    Science.gov (United States)

    Perumal, Shanmugapriya; Mahmud, Roziahanim

    2013-12-09

    The frequent occurrences of antibiotic-resistant biofilm forming pathogens have become global issue since various measures that had been taken to curb the situation led to failure. Euphorbia hirta, is a well-known ethnomedicinal plant of Malaysia with diverse biological activities. This plant has been used widely in traditional medicine for the treatment of gastrointestinal, bronchial and respiratory ailments caused by infectious agents. In the present study, chemical compositions of methanol extract of E. hirta L. aerial part was analyzed by gas chromatography and gas chromatography coupled to mass spectrometry. A relevant in vitro model was developed to assess the potency of the E. hirta extract to inhibit the bacterial biofilm formation as well as to eradicate the established biofilms. Besides biofilm, E. hirta extract was also evaluated for the inhibition efficacy on planktonic cells using tetrazolium microplate assay. For these purposes, a panel of clinically resistant pathogens and American type culture collection (ATCC) strains were used. The methanolic extract of aerial part of E. hirta was predominantly composed of terpenoid (60.5%) which is often regarded as an active entity accountable for the membrane destruction and biofilm cell detachment. The highest antibacterial effect of crude E. hirta extract was observed in the clinical isolates of Pseudomonas aeruginosa with minimum inhibitory concentration (MIC) value of 0.062 mg/ml. The extract also displayed potent biofilm inhibition and eradication activity against P. aeruginosa with minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) values of 0.25 mg/ml and 0.5 mg/ml, respectively. The crude methanol extract of E. hirta has proven to have interesting and potential anti-biofilm properties. The findings from this study will also help to establish a very promising anti-infective phytotherapeutical to be exploited in the pharmaceutical industries.

  16. Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance

    International Nuclear Information System (INIS)

    Gohno, Tatsuyuki; Seino, Yuko; Hanamura, Toru; Niwa, Toshifumi; Matsumoto, Mitsuyo; Yaegashi, Nobuo; Oba, Hanako; Kurosumi, Masafumi; Takei, Hiroyuki; Yamaguchi, Yuri; Hayashi, Shin-ichi

    2012-01-01

    To predict the efficacy of hormonal therapy at the individual-level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element–green fluorescence protein (ERE-GFP) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR, rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of Luminal A-type breast cancer samples according to ERE activity revealed that ERα mRNA expression correlated with ER target gene mRNA expression in the high-, but not the low-, ERE-activity group. On the other hand, the low-ERE-activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment

  17. New agents with potential leishmanicidal activity identified by virtual screening of chemical databases: New agents with potential leishmanicidal activity

    Directory of Open Access Journals (Sweden)

    Juan Rebollo

    2013-04-01

    Full Text Available Introduction and Objectives: Leishmaniosis, a disease caused by a protozoan parasite, remains a serious public health problem threatening about 350 million people around the world, of which 12 million are believed to be currently infected (WHO 2010. To date, there are no vaccines against the species of parasites and the treatment is based only on chemotherapy with toxic-, expensive- and inefficient- drugs. There is an urgent need for better drugs against Leishmania, the etiological agent of the disease. The main anti-leishmanial drug used in Colombia is meglumineantimoniate [chemical name according to the International Union of Pure and Applied Chemistry (IUPAC: Hydroxy-dioxostiborane; (2R,3R,4R,5S- 6-methylaminohexane-1,2,3,4,5-pentol, (C7H17NO5], which is not efficient in the treatment of infections caused by Leishmania braziliensis, the most prevalent specie in the Caribbean coast of Colombia. Methods: We performed an in silico virtual screening of several datasets including ChemBridge and Pubchem. We virtually screened a total of 28.755 compounds against a 3D model of 6-phosphoglucono -lactonase (6-PGL from Leishmania braziliensis to identify novel inhibitors.Molecular docking of databases was performed using the software Sybyl 8.0 and AutoDockVina. Results: The initial virtual screening using a structure-based method identified 10 compounds, which were later tested with AutodockVina and classified according to their docking scores. Conclusions: These novel and potential inhibitors constitute new drug candidates that must be biologically tested to define their value as an alternative chemotherapeutic agent in the treatment of these protozoan infections. Salud UIS 2013; 45 (1: 33-40

  18. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Kim Y

    2012-08-01

    insulin, and as a monotherapy for metformin-intolerant patients. Clinical research also remains to be carried out on the long-term effects of glucosuria and other potential effects of SGLT2 inhibitors, especially in view of the observed increase in the incidence of bladder and breast cancer. SGLT2 inhibitors represent a promising approach for the treatment of diabetes, and could potentially be an addition to existing therapies.Keywords: sodium-glucose cotransporter type 2, SGLT2, inhibitors, kidney, glucosuria, oral diabetes agent, weight loss

  19. Potential clinical and economic effects of homocyst(e)ine lowering.

    Science.gov (United States)

    Nallamothu, B K; Fendrick, A M; Rubenfire, M; Saint, S; Bandekar, R R; Omenn, G S

    Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable

  20. Addictive potential of modafinil and cross-sensitization with cocaine: a pre-clinical study.

    Science.gov (United States)

    Wuo-Silva, Raphael; Fukushiro, Daniela F; Borçoi, Aline R; Fernandes, Helaine A; Procópio-Souza, Roberta; Hollais, André W; Santos, Renan; Ribeiro, Luciana T C; Corrêa, Jussara M R M; Talhati, Fernanda; Saito, Luis P; Aramini, Tatiana C F; Kameda, Sonia R; Bittencourt, Lia R A; Tufik, Sergio; Frussa-Filho, Roberto

    2011-10-01

    Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  1. Clinically targeted screening for congenital CMV - potential for integration into the National Hearing Screening Programme.

    Science.gov (United States)

    Kadambari, S; Luck, S; Davis, A; Williams, Ej; Berrington, J; Griffiths, Pd; Sharland, M

    2013-10-01

    Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  2. Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters.

    Science.gov (United States)

    Kamel, Azza M; El-Sharkawy, Nahla M; Osman, Randa A; Abd El-Fattah, Eman K; El-Noshokaty, Essam; Abd El-Hamid, Thoraya; Kandeel, Eman Z

    2016-03-01

    B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs. This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters. The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry. Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  3. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  4. Using clinical cases to stimulate active learning in a short periodontal continuing professional development course.

    Science.gov (United States)

    Koole, Sebastiaan; Thevissen, Eric; Lindén, Ulf; Klinge, Björn; de Bruyn, Hugo

    2015-01-01

    A case-based approach was used in a two-day periodontal continuing professional development course as a strategy to stimulate active learning. The present study investigates the outcome of this course format in terms of feasibility, perceived efficiency as a learning approach and reported individual learning goals. The study was performed in five identical courses entitled'risk analysis and treatment in periodontal patients'at Malmö University between 2011-2014. Before the course, clinical cases were used to activate participants' prior knowledge and to attune their focus on the course content. During the course, cases were discussed to synchronise theory with practical application. A pre- and end-course questionnaire were developed to evaluate participants' characteristics (age, clinical expertise, experience and expectations), perceptions on feasibility and instructiveness and emerged individual learning goals. The participants (39 dentists and 78 dental hygienists) reported an average preparation time of 62 minutes (range 2-190) and had positive perceptions on the accessibility, instructiveness and difficulty of cases. Expectations ranged between refreshing, acquiring new knowledge and mastering the course subject. Most reported learning goals were related to daily clinical practice including the development of a treatment plan, when to continue non-surgical treatment or to extract teeth/perform surgery, the approach to periodontitis, how to motivate non-compliant patients and when to refer. Conclusion: The use of clinical cases to stimulate active learning in a short-term continuing professional development periodontal course was positively perceived by the dentists and dental hygienists in terms of feasibility and learning potential.

  5. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 2: Optimizing the Design of Human Abuse Potential Studies.

    Science.gov (United States)

    Sellers, Edward M

    2018-04-01

    This article discusses the conduct of a human abuse potential study as outlined in the Food and Drug Administration Final Guidance to Industry on Assessment of Abuse Potential. In addition, areas where alternative approaches should be considered are proposed. The design, end points, conduct, and interpretation of the human abuse potential study were reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk and expedite drug development. The guidance is based on regulatory needs and current scientific practices. However, the reliability and utility of such studies can be improved with better subject selection, data collection, standardization of data collection and staff training, and a better understanding of the measurement properties of the dependent measures. The guidance provides a useful framework for conduct of human abuse potential studies. However, design assumptions, poor choice of end points, failure to consider alternate approaches, and limited experience with interpretation can result in an inadequate study or one that does not fairly represent the abuse potential of a new chemical entity. Methodologic development is needed to strengthen the regulatory framework. The Food and Drug Administration or the National Institutes on Drug Abuse could take a targeted initiative to encourage this work.

  6. [Clinical characterization of audiometric and vestibular evoked myogenic potentials in patients with large vestibular aqueduct syndrome].

    Science.gov (United States)

    Wu, Jun; Wang, Jinling; Xie, Juan; Han, Liping; Gao, Lei

    2010-01-01

    To investigate the clinical and diagnostic characteristics of audiometric findings and vestibular-evoked myogenic potentials in patients with large vestibular aqueduct syndrome (LVAS). Thirty LVAS subjects (60 ears) recruited received pure tone audiometry, acoustic immittance, auditory brain stem responses (ABRs), distortion-product otoacoustic emission (DPOAE), Vestibular evoked myogenic potentials (VEMP) and caloric test, and the diagnostic significance of the results was analyzed. All 30 cases (60 ears) showed progressive and fluctuating hearing loss, while 16 cases experienced dizziness when hearing fluctuated. Most of our cases showed sensorineural hearing loss, and 47 ears (94.0%) showed air-bone gap in the low frequencies, with mean gaps of (43 +/- 17) dB HL at 250 Hz, (33 +/- 18) dB HL at 500 Hz, in which the middle ear function showed normal. The acoustically evoked short latency negative response (ASNR) with medium latency (3.06 +/- 0.52) ms was elicited from 18 ears (64.3%). The mean amplitude of vestibular evoked myogenic potentials (VEMP) of 42 ears was (147.10 +/- 107.55) microv, and the threshold of VEMP of 19 ears was 75 dB nHL, of 7 ears was 65 dB nHL. Characteristics of hearing performance, such as progressive and fluctuating hearing loss, air-bone gap at the low frequencies with normal middle ears, the ASNR, and increased amplitude and decreased threshold of the VEMPs, will help clinicians make initial diagnosis of LVAS, and provide a reference for further imaging examination.

  7. Clinically Viable Gene Expression Assays with Potential for Predicting Benefit from MEK Inhibitors.

    Science.gov (United States)

    Brant, Roz; Sharpe, Alan; Liptrot, Tom; Dry, Jonathan R; Harrington, Elizabeth A; Barrett, J Carl; Whalley, Nicky; Womack, Christopher; Smith, Paul; Hodgson, Darren R

    2017-03-15

    Purpose: To develop a clinically viable gene expression assay to measure RAS/RAF/MEK/ERK (RAS-ERK) pathway output suitable for hypothesis testing in non-small cell lung cancer (NSCLC) clinical studies. Experimental Design: A published MEK functional activation signature (MEK signature) that measures RAS-ERK functional output was optimized for NSCLC in silico NanoString assays were developed for the NSCLC optimized MEK signature and the 147-gene RAS signature. First, platform transfer from Affymetrix to NanoString, and signature modulation following treatment with KRAS siRNA and MEK inhibitor, were investigated in cell lines. Second, the association of the signatures with KRAS mutation status, dynamic range, technical reproducibility, and spatial and temporal variation was investigated in NSCLC formalin-fixed paraffin-embedded tissue (FFPET) samples. Results: We observed a strong cross-platform correlation and modulation of signatures in vitro Technical and biological replicates showed consistent signature scores that were robust to variation in input total RNA; conservation of scores between primary and metastatic tumor was statistically significant. There were statistically significant associations between high MEK ( P = 0.028) and RAS ( P = 0.003) signature scores and KRAS mutation in 50 NSCLC samples. The signatures identify overlapping but distinct candidate patient populations from each other and from KRAS mutation testing. Conclusions: We developed a technically and biologically robust NanoString gene expression assay of MEK pathway output, compatible with the quantities of FFPET routinely available. The gene signatures identified a different patient population for MEK inhibitor treatment compared with KRAS mutation testing. The predictive power of the MEK signature should be studied further in clinical trials. Clin Cancer Res; 23(6); 1471-80. ©2016 AACR See related commentary by Xue and Lito, p. 1365 . ©2016 American Association for Cancer Research.

  8. Therapeutic Potential of Tolerogenic Dendritic Cells in IBD: From Animal Models to Clinical Application

    Directory of Open Access Journals (Sweden)

    Raquel Cabezón

    2013-01-01

    Full Text Available The gut mucosa undergoes continuous antigenic exposure from food antigens, commensal flora derived ligands, and pathogens. This constant stimulation results in controlled inflammatory responses that are effectively suppressed by multiple factors. This tight regulation, necessary to maintain intestinal homeostasis, is affected during inflammatory bowel diseases (IBD resulting in altered immune responses to harmless microorganisms. Dendritic cells (DCs are sentinels of immunity, located in peripheral and lymphoid tissues, which are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of pathogen recognition receptors allows DCs to initiate immune responses. However, in the absence of danger signals, different DC subsets can induce active tolerance by inducing regulatory T cells (Treg, inhibiting inflammatory T helper cell responses, or both. Interestingly, several protocols to generate clinical grade tolerogenic DC (tol-DCs in vitro have been described, opening the possibility to restore the intestinal homeostasis to bacterial flora by cellular therapy. In this review, we discuss different DC subsets and their role in IBD. Additionally, we will review preclinical studies performed in animal models while describing recent characterization of tol-DCs from Crohn’s disease patients for clinical application.

  9. Antifungal potential of eugenyl acetate against clinical isolates of Candida species.

    Science.gov (United States)

    Musthafa, Khadar Syed; Hmoteh, Jutharat; Thamjarungwong, Benjamas; Voravuthikunchai, Supayang Piyawan

    2016-10-01

    The study evaluated the efficiency of eugenyl acetate (EA), a phytochemical in clove essential oil, against clinical isolates of Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. Minimum inhibitory concentrations (MIC) of EA against Candida isolates were in the range between 0.1% and 0.4% (v/v). Spot assay further confirmed the susceptibility of Candida isolates to the compound upon treatment with respective 1 × MIC. Growth profile measured in time kill study evidence that the compound at 1 × MIC and 1/2 × MIC retarded the growth of Candida cells, divulging the fungicidal activity. Light microscopic observation demonstrated that upon treated with EA, rough cell morphology, cell damage, and fragmented patterns were observed in C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata. Furthermore, unusual morphological changes of the organism were observed in scanning electron microscopic study. Therefore, it is validated that the compound could cause cell damage resulting in the cell death of Candida clinical isolates. Eventually, the compound at sub-MIC (0.0125% v/v) significantly inhibited serum-induced germ tube formation by C. albicans. Eugenyl acetate inhibited biofilm forming ability of the organisms as well as reduced the adherence of Candida cells to HaCaT keratinocytes cells. In addition, upon treatment with EA, the phagocytic activity of macrophages was increased significantly against C. albicans (P Candida infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Sleep-potentiated epileptiform activity in early thalamic injuries: Study in a large series (60 cases).

    Science.gov (United States)

    Losito, Emma; Battaglia, Domenica; Chieffo, Daniela; Raponi, Matteo; Ranalli, Domiziana; Contaldo, Ilaria; Giansanti, Cristina; De Clemente, Valentina; Quintiliani, Michela; Antichi, Eleonora; Verdolotti, Tommaso; de Waure, Chiara; Tartaglione, Tommaso; Mercuri, Eugenio; Guzzetta, Francesco

    2015-01-01

    The study aims at a better definition of continuous spike-waves during sleep (CSWS) with an early thalamic lesion, focusing on various grades of sleep-potentiated epileptiform activity (SPEA). Their possible relationship with different clinical features was studied to try to define prognostic factors of the epileptic disorder, especially relating to behavior/cognitive outcome, in order to improve prevention and treatment strategies. Sixty patients with early thalamic injury were followed since the first registration of SPEA with serial neurological, long term EEG monitoring and neuropsychological examinations, as well as neuroimaging and a detailed clinical history. They were classified in three different groups according to the sleep spike-waves (SW) quantification: electrical status epilepticus during sleep (ESES), more than 85% of slow sleep; overactivation between 50% and 85% and simple activation between 10 and 50%). Results were then examined also with a statistical analysis. In our series of CSWS occurring in early brain injured children with unilateral thalamic involvement there is a common neuropathologic origin but with various grades of SPEA severity. Statistical analysis showed that patients evolving toward ESES presented more commonly the involvement of the mediodorsal part of thalamus nuclei and a bilateral cortico-subcortical brain injury, epilepsy was more severe with a delayed onset; moreover, in the acute stage .ESES patients presented the worst behavior/cognitive performances. As to cognitive and behavior outcome, longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase appear linked to a poor outcome; some particular neuropathology (ischemic stroke and haemorrhagic infarction) as well as hydrocephalus shunting are associated with behavior disorders. Discrete features seem to support different underlying mechanisms in ESES patients in comparison with less severe SPEA; they represent negative

  11. Reviewing Clinical Effectiveness of Active Training Strategies of Platform-Based Ankle Rehabilitation Robots

    Directory of Open Access Journals (Sweden)

    Xiangfeng Zeng

    2018-01-01

    Full Text Available Objective. This review aims to provide a systematical investigation of clinical effectiveness of active training strategies applied in platform-based ankle robots. Method. English-language studies published from Jan 1980 to Aug 2017 were searched from four databases using key words of “Ankle∗” AND “Robot∗” AND “Effect∗ OR Improv∗ OR Increas∗.” Following an initial screening, three rounds of discrimination were successively conducted based on the title, the abstract, and the full paper. Result. A total of 21 studies were selected with 311 patients involved; of them, 13 studies applied a single group while another eight studies used different groups for comparison to verify the therapeutic effect. Virtual-reality (VR game training was applied in 19 studies, while two studies used proprioceptive neuromuscular facilitation (PNF training. Conclusion. Active training techniques delivered by platform ankle rehabilitation robots have been demonstrated with great potential for clinical applications. Training strategies are mostly combined with one another by considering rehabilitation schemes and motion ability of ankle joints. VR game environment has been commonly used with active ankle training. Bioelectrical signals integrated with VR game training can implement intelligent identification of movement intention and assessment. These further provide the foundation for advanced interactive training strategies that can lead to enhanced training safety and confidence for patients and better treatment efficacy.

  12. Harnessing the potential clinical use of medicinal plants as anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Campbell-Tofte JI

    2012-08-01

    Full Text Available Joan IA Campbell-Tofte,1 Per Mølgaard,2 Kaj Winther11Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark; 2Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: Diabetes is a metabolic disorder arising from complex interactions between multiple genetic and/or environmental factors. The characteristic high blood sugar levels result from either lack of the hormone insulin (type 1 diabetes, T1D, or because body tissues do not respond to the hormone (type 2 diabetes, T2D. T1D patients currently need exogenous insulin for life, while for T2D patients who do not respond to diet and exercise regimes, oral anti-diabetic drugs (OADs and sometimes insulin are administered to help keep their blood glucose as normal as possible. As neither the administration of insulin nor OADs is curative, many patients develop tissue degenerative processes that result in life-threatening diabetes comorbidities. Several surveys of medicinal plants used as anti-diabetic agents amongst different peoples have been published. Some of this interest is driven by the ongoing diabetes pandemic coupled with the inadequacies associated with the current state of-the-art care and management of the syndrome. However, there is a huge cleft between traditional medicine and modern (Western medicine, with the latter understandably demanding meaningful and scientific validation of anecdotal evidence for acceptance of the former. The main problems for clinical evaluation of medicinal plants with promising anti-diabetic properties reside both with the complexity of components of the plant materials and with the lack of full understanding of the diabetes disease etiology. This review is therefore focused on why research activities involving an integration of Systems Biology-based technologies of pharmacogenomics, metabolomics, and bioinformatics with standard clinical data

  13. Clinical potential of carfilzomib in the treatment of relapsed and refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    Gupta VA

    2013-05-01

    Full Text Available Vikas A Gupta, Ajay K Nooka, Sagar Lonial, Lawrence H BoiseDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USAAbstract: Treatment of refractory and/or relapsed multiple myeloma has been a challenging problem for over 20 years. However, we have made significant progress addressing this disease with the use of bortezomib, the first in class proteasome inhibitor, and the immunomodulatory agents, thalidomide and lenalidomide. Carfilzomib, the second-generation proteasome inhibitor, has also been approved for treatment of relapsed/refractory multiple myeloma. Carfilzomib is a highly selective and potent inhibitor of proteasome chymotrypsin-like activity. Phase I and II clinical trials have reported an acceptable toxicity profile, with manageable thrombocytopenia and anemia being the most common side effects. Peripheral neuropathy, a frequent dose-limiting side effect of bortezomib, was rare. Further, carfilzomib demonstrated encouraging single-agent activity and appeared to be effective even in patients refractory to bortezomib. Based on these promising data, carfilzomib is moving forward into Phase III trials for relapsed multiple myeloma and is also being investigated as front-line combination therapy for patients with newly diagnosed myeloma.Keywords: proteasome inhibitor, bortezomib, pharmacology, safety, efficacy

  14. Could one single dichotomous noise cause resonant activation for exit time over potential barrier?

    International Nuclear Information System (INIS)

    Li Jinghui

    2008-01-01

    This paper studies the mean first passage time (or exit time, or escape time) over the non-fluctuating potential barrier for a system driven only by a dichotomous noise. It finds that the dichotomous noise can make the particles escape over the potential barrier, in some circumstances; but in other circumstances, it can not. In the case that the particles escape over the potential barrier, a resonant activation phenomenon for the mean first passage time over the potential barrier is obtained. (general)

  15. Clinical assessment of the effect of digital filtering on the detection of ventricular late potentials

    Directory of Open Access Journals (Sweden)

    P.R. Benchimol-Barbosa

    2002-11-01

    Full Text Available Ventricular late potentials are low-amplitude signals originating from damaged myocardium and detected on the body surface by ECG filtering and averaging. Digital filters present in commercial equipment may interfere with the ability of arrhythmia stratification. We compared 40-Hz BiSpec (BI and classical 40- to 250-Hz band-pass Butterworth bidirectional (BD filters in terms of impact on time domain variables and diagnostic properties. In a transverse retrospective age-adjusted case-control study, 221 subjects with sinus rhythm without bundle branch block were divided into three groups after signal-averaged ECG acquisition: GI (N = 40, clinically normal controls, GII (N = 158, subjects with coronary heart disease without sustained monomorphic ventricular tachycardia (SMVT, and GIII (N = 23, subjects with heart disease and documented SMVT. Conventional variables analyzed from vector magnitude data after averaging to 0.3 µV final noise were obtained by application of each filter to the averaged signal, and evaluated in pairs by numerical comparison and by diagnostic agreement assessment, using conventional and optimized thresholds of normality. Significant differences were found between BI and BD variables in all groups, with diagnostic results showing significant disagreement between both filters [kappa value of 0.61 (P<0.05 for GII and 0.31 for GIII (P = NS]. Sensitivity for SMVT was lower with BI than with BD (65.2 vs 91.3%, respectively, P<0.05. Filters provided significantly different numerical and diagnostic results and the BI filter showed only limited clinical application to risk stratification of ventricular arrhythmia.

  16. The potential for delegation of clinical care in general dental practice.

    Science.gov (United States)

    Evans, C; Chestnutt, I G; Chadwick, B L

    2007-12-22

    This study describes the proportion and volume of work undertaken in primary dental care that could be delegated to hygienists and therapists. Data on treatment provision, both NHS and private, over one course of treatment for 850 consecutively attending patients at 17 dental practices, selected to be representative of a range of socioeconomic, urban and rural environments, were extracted from case records. The 850 patients attended on 2,433 occasions. Diagnostic examination accounted for 833 (34.2%) visits, while simple, intermediate and complex restorative interventions and other complex interventions accounted for 500 (20.5%), 361 (14.8%), 365 (15%) and 374 (15.4%) visits respectively. The total time required to provide the care was 42,800 minutes, of which 6,550 (15.3%) were devoted to diagnostic examinations, while 10,485 (24.5%), 7,935 (18.5%) and 11,790 (27.5%) were taken up with simple, intermediate and complex restorative care. Other complex interventions accounted for 6,040 (14.2%) minutes. Assuming that dental therapists are permitted to undertake simple and intermediate restorative interventions, they could provide 35.3% of care when number of visits is utilised as the outcome measure, but 43% of the clinical time taken to provide care. Delegation of diagnostic and treatment planning powers to dental therapists could potentially result in 69.5% of visits and 58.3% of clinical time being provided by therapists. These data imply that a considerable proportion of work in UK general dental practice could be delegated to dental hygienists and therapists.

  17. Clinical realism: a new literary genre and a potential tool for encouraging empathy in medical students.

    Science.gov (United States)

    McDonald, Paula; Ashton, Katy; Barratt, Rachel; Doyle, Simon; Imeson, Dorrie; Meir, Amos; Risser, Gregoire

    2015-07-03

    Empathy has been re-discovered as a desirable quality in doctors. A number of approaches using the medical humanities have been advocated to teach empathy to medical students. This paper describes a new approach using the medium of creative writing and a new narrative genre: clinical realism. Third year students were offered a four week long Student Selected Component (SSC) in Narrative Medicine and Creative Writing. The creative writing element included researching and creating a character with a life-changing physical disorder without making the disorder the focus of the writing. The age, gender, social circumstances and physical disorder of a character were randomly allocated to each student. The students wrote repeated assignments in the first person, writing as their character and including details of living with the disorder in all of their narratives. This article is based on the work produced by the 2013 cohort of students taking the course, and on their reflections on the process of creating their characters. Their output was analysed thematically using a constructivist approach to meaning making. This preliminary analysis suggests that the students created convincing and detailed narratives which included rich information about living with a chronic disorder. Although the writing assignments were generic, they introduced a number of themes relating to illness, including stigma, personal identity and narrative wreckage. Some students reported that they found it difficult to relate to "their" character initially, but their empathy for the character increased as the SSC progressed. Clinical realism combined with repeated writing exercises about the same character is a potential tool for helping to develop empathy in medical students and merits further investigation.

  18. Nuclear medicine in the acute clinical setting: indications, imaging findings, and potential pitfalls.

    Science.gov (United States)

    Uliel, Livnat; Mellnick, Vincent M; Menias, Christine O; Holz, Andrew L; McConathy, Jonathan

    2013-01-01

    Nuclear medicine imaging provides valuable functional information that complements information obtained with anatomic imaging techniques in the evaluation of patients with specific acute clinical manifestations. Nuclear medicine studies are most often used in conjunction with other imaging modalities and as a problem-solving tool. Under certain circumstances a nuclear medicine study may be indicated as the first-line imaging modality, as in the case of renal scintigraphy for transplant dysfunction in the early postoperative period. Nuclear imaging may be preferred when a conventional first-line study is contraindicated or when it is important to minimize radiation exposure. The portability of nuclear imaging offers particular advantages for the evaluation of critically ill patients whose clinical condition is unstable and who cannot be safely transported out of the intensive care unit. The ability to visualize physiologic and pathophysiologic processes over relatively long time periods without adding to the patient's radiation exposure contributes to the high diagnostic sensitivity of several types of nuclear medicine studies. Viewing the acquired images in the cine mode adds to the value of these studies for diagnosing and characterizing dynamic abnormalities such as intermittent internal bleeding and bile or urine leakage. In this pictorial review, the spectrum of nuclear medicine studies commonly performed in the acute care setting is reviewed according to body systems and organs, with detailed descriptions of the indications, technical considerations, findings, and potential pitfalls of each type of study. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.332125098/-/DC1.

  19. Transnational Activism and Free Trade. Exploring the Emancipatory Potentials of Global Civil Society

    NARCIS (Netherlands)

    Del Felice, M.C.

    2012-01-01

    This article explores the alleged emancipatory potential of global civil society as regards transnational activism to promote fair trade. It examines the case of transnational activism on European Free Trade Agreements, with illustrations from the Stop EPAs campaign and activism relating to the

  20. Aging Adults Learning New Avocations: Potential Increases in Activity among Educated Baby-Boomers

    Science.gov (United States)

    Johnson, Marcus Lee; Bungum, Timothy

    2008-01-01

    The potential benefits, drawbacks, and preferences of activity (both physical and nonphysical) among Baby-Boomers were the foci of this study. This study included 56 survey participants and 5 interviewees. Descriptive statistics illustrated a preference towards low impact physical activity and cognitively enriching nonphysical activities. Time…

  1. Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics.

    Directory of Open Access Journals (Sweden)

    Divakara S S M Uppu

    Full Text Available Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (blaNDM-1 producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMs that restore the antibacterial efficacy (enhancement by >80-1250 fold of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates. Organismic studies showed that bacteria had an increased and faster uptake of tetracycline in the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover, bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.

  2. Correction: Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics.

    Directory of Open Access Journals (Sweden)

    Divakara S S M Uppu

    Full Text Available Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (blaNDM-1 producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMsthat restore the antibacterial efficacy (enhancement by >80-1250 fold of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates.Organismic studies showed that bacteria had an increased and faster uptake of tetracyclinein the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover,bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.

  3. Secukinumab, a novel anti–IL-17A antibody, shows low immunogenicity potential in human in vitro assays comparable to other marketed biotherapeutics with low clinical immunogenicity

    Science.gov (United States)

    Karle, Anette; Spindeldreher, Sebastian; Kolbinger, Frank

    2016-01-01

    ABSTRACT Secukinumab is a human monoclonal antibody that selectively targets interleukin-17A and has been demonstrated to be highly efficacious in the treatment of moderate to severe plaque psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. Biotherapeutics—including monoclonal antibodies (mAbs)—can be immunogenic, leading to formation of anti-drug antibodies (ADAs) that can result in unwanted effects, including hypersensitivity reactions or compromised therapeutic efficacy. To gain insight into possible explanations for the clinically observed low immunogenicity of secukinumab, we evaluated its immunogenicity potential by applying 2 different in vitro assays: T-cell activation and major histocompatibility complex–associated peptide proteomics (MAPPs). For both assays, monocyte-derived dendritic cells (DCs) from healthy donors were exposed in vitro to biotherapeutic proteins. DCs naturally process proteins and present the derived peptides in the context of human leukocyte antigen (HLA)-class II. HLA-DR–associated biotherapeutic-derived peptides, representing potential T–cell epitopes, were identified in the MAPPs assay. In the T-cell assay, autologous CD4+ T cells were co-cultured with secukinumab-exposed DCs and T-cell activation was measured by proliferation and interleukin-2 secretion. In the MAPPs analysis and T-cell activation assays, secukinumab consistently showed relatively low numbers of potential T-cell epitopes and low T-cell response rates, respectively, comparable to other biotherapeutics with known low clinical immunogenicity. In contrast, biotherapeutics with elevated clinical immunogenicity rates showed increased numbers of potential T-cell epitopes and increased T-cell response rates in T-cell activation assays, indicating an approximate correlation between in vitro assay results and clinical immunogenicity incidence. PMID:26817498

  4. In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1.

    Science.gov (United States)

    Pak, Y Anne; Long, Amanda J; Annes, William F; Witcher, Jennifer W; Knadler, Mary Pat; Ayan-Oshodi, Mosun A; Mitchell, Malcolm I; Leese, Phillip; Hillgren, Kathleen M

    2017-02-01

    Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design. In vitro investigations determined the prodrug (LY2140023 monohydrate) is a substrate of PEPT1 with K m value of approximately 30 µM, whereas the active moiety (LY404039) is not a PEPT1 substrate. In addition, among the eight known PEPT1 substrates evaluated in vitro, valacyclovir was the most potent inhibitor (IC 50 = 0.46 mM) of PEPT1-mediated uptake of the prodrug. Therefore, a clinical drug interaction study was conducted to evaluate the potential interaction between the prodrug and valacyclovir in healthy subjects. No effect of coadministration was observed on the pharmacokinetics of the prodrug, valacyclovir, or either of their active moieties. Although in vitro studies showed potential for the prodrug and valacyclovir interaction via PEPT1, an in vivo study showed no interaction between these two drugs. PEPT1 does not appear to easily saturate because of its high capacity and expression in the intestine. Thus, a clinical interaction at PEPT1 is unlikely even with a compound with high affinity for the transporter. Copyright © 2017 by The Author(s).

  5. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Chun-Chieh Wu

    2015-05-01

    Full Text Available Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment. Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p < 0.0001. Nude mouse (BALB/c-nu experiments showed that the increased tumor volume ratios in colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167. The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015. In addition to the well-known direct colchicine–tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience.

  6. Detection of activated platelets using activation-specific monoclonal antibody (SZ-51) in clinical disorders

    International Nuclear Information System (INIS)

    Wu Guoxin; Li Fugang; Li Jianyong; Ruan Changgeng

    1991-10-01

    A direct test for activated platelets in whole blood was developed by radioimmunoassay with 125 I labeled SZ-51, an antibody specific for an α-granule membrane protein (GMP-140) that associates with the platelet surface during secretion. The assay had sufficient sensitivity to detect as few as 2% activated platelets. In 50 normal subjects, minimal GMP-140 molecules per platelet were expressed on the surface of circulating platelets. Ten patients undergoing cardiopulmonary bypass had transiently increased expression of GMP-140 molecules during the bypass procedure, especially at the end of bypass. Evaluation of 18 patients with epidemic hemorrhagic fever (EHF) has shown that the number of GMP-140 molecules on the platelet surface was closely related to the four different phases of EHF. In six patients suffered from acute myocardial infarction (AMI), the number of GMP-140 molecules changed with the procession of AMI and the highest occurred 48 h after AMI. The GMP-140 molecules were also increased in patients with asthma attack (n = 14), but not in patients with idiopathic thrombocytopenic purpura (n = 11) and diabetic mellitus (n = 48). Taken together, these studies suggest that activated platelet can be reliably measured in whole blood using radiolabeled SZ-51 antibody and the detection of activated platelets is potentially useful in identifying patients with certain thrombotic disorders and others

  7. Comparison of the virulence potential of Acinetobacter strains from clinical and environmental sources.

    Directory of Open Access Journals (Sweden)

    Azam F Tayabali

    Full Text Available Several Acinetobacter strains have utility for biotechnology applications, yet some are opportunistic pathogens. We compared strains of seven Acinetobacter species (baumannii, Ab; calcoaceticus, Ac; guillouiae, Ag; haemolyticus, Ah; lwoffii, Al; junii, Aj; and venetianus, Av-RAG-1 for their potential virulence attributes, including proliferation in mammalian cell conditions, haemolytic/cytolytic activity, ability to elicit inflammatory signals, and antibiotic susceptibility. Only Ah grew at 10(2 and 10(4 bacteria/well in mammalian cell culture medium at 37°C. However, co-culture with colonic epithelial cells (HT29 improved growth of all bacterial strains, except Av-RAG-1. Cytotoxicity of Ab and Ah toward HT29 was at least double that of other test bacteria. These effects included bacterial adherence, loss of metabolism, substrate detachment, and cytolysis. Only Ab and Ah exhibited resistance to killing by macrophage-like J774A.1 cells. Haemolytic activity of Ah and Av-RAG-1 was strong, but undetectable for other strains. When killed with an antibiotic, Ab, Ah, Aj and Av-RAG-1 induced 3 to 9-fold elevated HT29 interleukin (IL-8 levels. However, none of the strains altered levels of J774A.1 pro-inflammatory cytokines (IL-1β, IL-6 and tumor necrosis factor-α. Antibiotic susceptibility profiling showed that Ab, Ag and Aj were viable at low concentrations of some antibiotics. All strains were positive for virulence factor genes ompA and epsA, and negative for mutations in gyrA and parC genes that convey fluoroquinolone resistance. The data demonstrate that Av-RAG-1, Ag and Al lack some potentially harmful characteristics compared to other Acinetobacter strains tested, but the biotechnology candidate Av-RAG-1 should be scrutinized further prior to widespread use.

  8. Comparison of the Virulence Potential of Acinetobacter Strains from Clinical and Environmental Sources

    Science.gov (United States)

    Tayabali, Azam F.; Nguyen, Kathy C.; Shwed, Philip S.; Crosthwait, Jennifer; Coleman, Gordon; Seligy, Verner L.

    2012-01-01

    Several Acinetobacter strains have utility for biotechnology applications, yet some are opportunistic pathogens. We compared strains of seven Acinetobacter species (baumannii, Ab; calcoaceticus, Ac; guillouiae, Ag; haemolyticus, Ah; lwoffii, Al; junii, Aj; and venetianus, Av-RAG-1) for their potential virulence attributes, including proliferation in mammalian cell conditions, haemolytic/cytolytic activity, ability to elicit inflammatory signals, and antibiotic susceptibility. Only Ah grew at 102 and 104 bacteria/well in mammalian cell culture medium at 37°C. However, co-culture with colonic epithelial cells (HT29) improved growth of all bacterial strains, except Av-RAG-1. Cytotoxicity of Ab and Ah toward HT29 was at least double that of other test bacteria. These effects included bacterial adherence, loss of metabolism, substrate detachment, and cytolysis. Only Ab and Ah exhibited resistance to killing by macrophage-like J774A.1 cells. Haemolytic activity of Ah and Av-RAG-1 was strong, but undetectable for other strains. When killed with an antibiotic, Ab, Ah, Aj and Av-RAG-1 induced 3 to 9-fold elevated HT29 interleukin (IL)-8 levels. However, none of the strains altered levels of J774A.1 pro-inflammatory cytokines (IL-1β, IL-6 and tumor necrosis factor-α). Antibiotic susceptibility profiling showed that Ab, Ag and Aj were viable at low concentrations of some antibiotics. All strains were positive for virulence factor genes ompA and epsA, and negative for mutations in gyrA and parC genes that convey fluoroquinolone resistance. The data demonstrate that Av-RAG-1, Ag and Al lack some potentially harmful characteristics compared to other Acinetobacter strains tested, but the biotechnology candidate Av-RAG-1 should be scrutinized further prior to widespread use. PMID:22655033

  9. Proven and potential clinical benefits of washing red blood cells before transfusion: current perspectives

    Directory of Open Access Journals (Sweden)

    Schmidt AE

    2016-08-01

    Full Text Available Amy E Schmidt, Majed A Refaai, Scott A Kirkley, Neil Blumberg Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA Abstract: Red blood cells (RBCs are washed for a variety of reasons such as to remove excess potassium, cytokines, and other allergen proteins from the supernatant and/or to mitigate the effects of the storage lesion. The storage lesion is a product of RBC aging and include leakage of potassium and chloride from the RBCs, depletion of 2,3-diphosphoglycerate and adenosine triphosphate, loss of phospholipids and cholesterol, exposure of phosphatidylserine, elaboration of lipid mediators, loss of glutathione, autoxidation of hemoglobin to methemoglobin contributing to decreased blood flow viscosity and adherence to endothelial cells, increased microparticle formation, and disruption of NO-mediated vasodilation. A storage lesion is thought to be caused in part by oxidative stress, which is characterized by functional and structural changes to the RBCs. The effects of the RBC storage lesion on patient morbidity and mortality have been studied intensively with mixed results. Here, we will summarize the potential benefits of RBC washing. Notably, all patient-based studies on washed RBCs are single-center, small randomized studies or observational data, which await replication and tests of generalizability. Some of the most promising preliminary data suggest that washed transfusions of red cells and platelets reduce mortality in low risk, younger patients with acute myeloid leukemia, mitigate lung injury, and substantially reduce mortality in cardiac surgery. Larger randomized trials to replicate or refute these findings are urgently needed and, most importantly, have the potential to strikingly improve clinical outcomes following transfusion. Keywords: washed blood, transfusion, immunomodulation, red blood cell

  10. Activism or Slacktivism? The Potential and Pitfalls of Social Media in Contemporary Student Activism

    Science.gov (United States)

    Cabrera, Nolan L.; Matias, Cheryl E.; Montoya, Roberto

    2017-01-01

    The emergence of social media has greatly influenced 21st-century student activism. It has also given rise to the birth of "slacktivism," an online form of self-aggrandizing, politically ineffective activism. This theoretical article delves into the conceptualizations of what constitutes student activism versus slacktivism in a digital…

  11. Frozen blood products: clinically effective and potentially ideal for remote Australia.

    Science.gov (United States)

    Holley, A; Marks, D C; Johnson, L; Reade, M C; Badloe, J F; Noorman, F

    2013-01-01

    The development of effective cryopreservation techniques for both red blood cells and platelets, which maintain ex vivo biological activity, in combination with frozen plasma, provides for a unique blood banking strategy. This technology greatly enhances the storage life of these products. The rationale and potential advantages of using cryopreservation techniques for the provision of blood products to remote and military environments have been effectively demonstrated in several conflicts over the last decade. Current haemostatic resuscitation doctrine for the exsanguinating patient supports the use of red blood cells, platelets and frozen plasma early in the resuscitation. We believe an integrated fresh-frozen blood bank inventory could facilitate provision of blood products, not only in the military setting but also in regional Australia, by overcoming many logistic and geographical challenges. The processes involved in production and point of care thawing are sufficiently well developed and achievable to make this technology a viable option. The potential limitations of cryopreservation and subsequent product thawing need to be considered if such a strategy is to be developed. A substantial body of international experience using cryopreserved products in remote settings has already been accrued. This experience provides a template for the possible creation of an Australian integrated fresh-frozen blood bank inventory that could conceivably enhance the care of patients in both regional Australia and in the military setting.

  12. Potential for Bacteriophage Endolysins to Supplement or Replace Antibiotics in Food Production and Clinical Care

    Directory of Open Access Journals (Sweden)

    Michael J. Love

    2018-02-01

    Full Text Available There is growing concern about the emergence of bacterial strains showing resistance to all classes of antibiotics commonly used in human medicine. Despite the broad range of available antibiotics, bacterial resistance has been identified for every antimicrobial drug developed to date. Alarmingly, there is also an increasing prevalence of multidrug-resistant bacterial strains, rendering some patients effectively untreatable. Therefore, there is an urgent need to develop alternatives to conventional antibiotics for use in the treatment of both humans and food-producing animals. Bacteriophage-encoded lytic enzymes (endolysins, which degrade the cell wall of the bacterial host to release progeny virions, are potential alternatives to antibiotics. Preliminary studies show that endolysins can disrupt the cell wall when applied exogenously, though this has so far proven more effective in Gram-positive bacteria compared with Gram-negative bacteria. Their potential for development is furthered by the prospect of bioengineering, and aided by the modular domain structure of many endolysins, which separates the binding and catalytic activities into distinct subunits. These subunits can be rearranged to create novel, chimeric enzymes with optimized functionality. Furthermore, there is evidence that the development of resistance to these enzymes may be more difficult compared with conventional antibiotics due to their targeting of highly conserved bonds.

  13. Functional Brain Activation in Response to a Clinical Vestibular Test Correlates with Balance.

    Science.gov (United States)

    Noohi, Fatemeh; Kinnaird, Catherine; DeDios, Yiri; Kofman, Igor S; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

    2017-01-01

    The current study characterizes brain fMRI activation in response to two modes of vestibular stimulation: Skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either a vestibulo-spinal reflex [saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)], or an ocular muscle response [utricle-mediated ocular VEMP (oVEMP)]. Research suggests that the skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for subjects than the high decibel tones required to elicit VEMPs. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of brain activity. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that pneumatically powered skull taps would elicit a similar pattern of brain activity as shown in previous studies. Our results provide the first evidence of using pneumatically powered skull taps to elicit vestibular activity inside the MRI scanner. A conjunction analysis revealed that skull taps elicit overlapping activation with auditory tone bursts in the canonical vestibular cortical regions. Further, our postural control assessments revealed that greater amplitude of brain activation in response to vestibular stimulation was associated with better balance control for both techniques. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects, highlighting the utility of this approach for future clinical and basic science research.

  14. Cleveland Clinic television series enhances branding in active market.

    Science.gov (United States)

    Rees, T

    2001-01-01

    "Medical Miracles" premiered April 26. It is an information-packed series of programs showcasing The Cleveland Clinic's advanced medical practices. The Cleveland Clinic teamed with local NBC-affiliate, WKYC to develop half-hour shows on topics including neuro-sciences, orthopedics, eye, heart, pediatrics and cancer. As of this writing, three of the half-hour shows already have aired. They will resume in September, October and November, following a summer break. The collaboration is a healthy prospect all the way around. For Cleveland Clinic, it provides highly credible visibility in a competitive marketplace. And, according to WKYC president and general manager, Brooke Spectorsky, " Medical news and information is a high priority among our viewers."

  15. Fern extracts potentiate fluconazole activity and inhibit morphological changes in Candida species

    Directory of Open Access Journals (Sweden)

    Maria A. Freitas

    2017-11-01

    Conclusions: The extracts obtained from the fern species L. venustum and P. calomelanos dose not present significant antifungal activity. However, P. calomelanos potentiates the activity of fluconazole and both extracts inhibits the morphological changes in Candida species, indicating that they have potential pharmacological activity as modulators of fungal biology. Therefore, novel studies are required to characterize the interference of these extracts in the virulence and pathogenicity of Candida species as well as the potential of fern species to treat fungal infections.

  16. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

  17. National physical activity surveillance: Users of wearable activity monitors as a potential data source

    Directory of Open Access Journals (Sweden)

    John D. Omura, MD

    2017-03-01

    Full Text Available The objective of this study was to assess usage patterns of wearable activity monitors among US adults and how user characteristics might influence physical activity estimates from this type of sample. We analyzed data on 3367 respondents to the 2015 HealthStyles survey, an annual consumer mail panel survey conducted on a nationwide sample. Approximately 1 in 8 respondents (12.5% reported currently using a wearable activity monitor. Current use varied by sex, age, and education level. Use increased with physical activity level from 4.3% for inactive adults to 17.4% for active adults. Overall, 49.9% of all adults met the aerobic physical activity guideline, while this prevalence was 69.5% among current activity monitor users. Our findings suggest that current users of wearable activity monitors are not representative of the overall US population. Estimates of physical activity levels using data from wearable activity monitors users may be an overestimate and therefore data from users alone may have a limited role in physical activity surveillance.

  18. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles.

    Science.gov (United States)

    Nazıroğlu, Mustafa; Muhamad, Salina; Pecze, Laszlo

    2017-07-01

    In etiology of Alzheimer's disease (AD), involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Several nanoparticles such as titanium dioxide, silica dioxide, silver and zinc oxide have been experimentally using for treatment of neurological disease. In the last decade, there has been a great interest on combination of antioxidant bioactive compounds such as selenium (Se) and flavonoids with the oxidant nanoparticles in AD. We evaluated the most current data available on the physiological effects of oxidant and antioxidant nanoparticles. Areas covered: Oxidative nanoparticles decreased the activities of reactive oxygen species (ROS) scavenging enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase in the brain of rats and mice. However, Se-rich nanoparticles in small size (5-15 nm) depleted Aβ formation through decreasing ROS production. Reports on low levels of Se in blood and tissue samples and the low activities of GSH-Px, catalase and SOD enzymes in AD patients and animal models support the proposed crucial role of oxidative stress in the pathogenesis of AD. Expert commentary: In conclusion, present literature suggests that Se-rich nanoparticles appeared to be a potential therapeutic compound for the treatment of AD.

  19. Potential role of stem cells in severe spinal cord injury: current perspectives and clinical data

    Directory of Open Access Journals (Sweden)

    Paspala SA

    2012-09-01

    Full Text Available Syed AB Paspala,1,2 Sandeep K Vishwakarma,1 Tenneti VRK Murthy,2 Thiriveedi N Rao,2 Aleem A Khan11PAN Research Foundation, CARE, 2The Institute of Medical Sciences, Hyderabad, IndiaAbstract: Stem cell transplantation for spinal cord injury (SCI along with new pharmacotherapy research offers the potential to restore function and ease the associated social and economic burden in the years ahead. Various sources of stem cells have been used in the treatment of SCI, but the most convincing results have been obtained with neural progenitor cells in preclinical models. Although the use of cell-based transplantation strategies for the repair of chronic SCI remains the long sought after holy grail, these approaches have been to date the most successful when applied in the subacute phase of injury. Application of cell-based strategies for the repair and regeneration of the chronically injured spinal cord will require a combinational strategy that may need to include approaches to overcome the effects of the glial scar, inhibitory molecules, and use of tissue engineering strategies to bridge the lesion. Nonetheless, cell transplantation strategies are promising, and it is anticipated that the Phase I clinical trials of some form of neural stem cell-based approach in SCI will commence very soon.Keywords: stem cell therapy, regeneration, spinal cord injury, cell dosing, cell tracking

  20. Dermotropic Leishmania donovani in Sri Lanka: visceralizing potential in clinical and preclinical studies.

    Science.gov (United States)

    Kariyawasam, K K G D U L; Selvapandiyan, A; Siriwardana, H V Y D; Dube, A; Karunanayake, P; Senanayake, S A S C; Dey, R; Gannavaram, S; Nakhasi, H L; Karunaweera, N D

    2017-11-08

    The visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental infection models. CL patients (n = 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice with L. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain of L. donovani-1S (control). Cytokine (IL-10, IFN-γ) release patterns of splenocytes and lymph node cell cultures derived from mice primed with experimental infections (with either test or control parasites) revealed significantly high IFN-γ response associated with test mice with CL, while prominent IL-10 levels were observed in association with control mice with VL. Furthermore, diminished infection efficiency, intracellular growth and survival of L. donovani-SL parasites compared with L. donovani-1S were evident through in vitro macrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature of L. donovani-SL suggesting natural attenuation of virulence of local parasite strains.

  1. Clinical implication of cervical vestibular evoked myogenic potentials in benign paroxysmal positional vertigo.

    Science.gov (United States)

    Chang, Mun Young; Shin, Ji Ho; Oh, Kyung Hyun; Hong, Young Ho; Mun, Seog-Kyun

    2017-02-01

    To evaluate the value of cervical vestibular evoked myogenic potential (cVEMP) as a prognostic factor for benign paroxysmal positional vertigo (BPPV). We reviewed 65 patients with BPPV who underwent cVEMP. Patients were divided into two groups according to resistance to the repositioning maneuver. Univariable and multivariable analyses were performed with age, gender, affected semicircular canal, affected side and cVEMP parameters to find the associated factors for resistance to the repositioning maneuver. From univariable analysis, cVEMP interaural amplitude difference (IAD) ratio, the affected semicircular canal and the affected side showed a better association (p<0.10) with resistance to the repositioning maneuver. With multivariable analysis, decreased cVEMP IAD ratio at the affected side (⩽-25%) (p=0.043, OR=4.934) and the posterior semicircular canal (p=0.049, OR=3.780) remained as associated factors. Decreased cVEMP IAD ratio at the affected side is associated with resistance to the repositioning maneuver. BPPV patients with decreased cVEMP IAD ratio at the affected side have a higher likelihood of their BPPV persisting after a single repositioning maneuver. cVEMP test may provide a prognosis of BPPV. A decreased cVEMP IAD ratio at the affected side may be prognostic of BPPV not resolving after a single repositioning maneuver. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  2. What are the potential benefits of clinical beta-cell imaging in diabetes mellitus?

    Science.gov (United States)

    Göke, Burkhard

    2010-05-01

    Previously, studies of the endocrine pancreatic beta-cell were mainly performed ex vivo by morphological means. This data supported the analysis of pathophysiological changes in the pancreatic islet during insults such as diabetes mellitus. Metabolic testing of the pancreatic islet by assaying hormone parameters such als plasma insulin or C-peptide combined with more or less sophisticated calculations allowed conclusions about states of insulin resistance or secretory failure. It also allowed certain correlations of endocrine function with beta-cell mass. Today, with firmer pathophysiological concepts about beta-cell failure, modern protocols of islet transplantation, and drugs on the market coming with promises of preservation or even expansion of beta-cell mass in diabetes mellitus it has become very attractive to search for tools measuring beta-cell mass, if possible even repeatingly in the same organism in vivo. From a clinical point of view, the potential of pancreatic beta-cell mass imaging technologies is looked upon with high expectations. Methodologically, the decisive question is whether it is likely that future beta-cell imaging will provide significant advantages over the metabolic methods already in hand. With new in vivo tools, studies of beta-cell mass and function may offer even new approaches stratifying patients to anti-diabetic therapies.

  3. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  4. Arm and wrist surface potential mapping for wearable ECG rhythm recording devices: a pilot clinical study

    Science.gov (United States)

    Lynn, W. D.; Escalona, O. J.; McEneaney, D. J.

    2013-06-01

    This study addresses an important question in the development of a ECG device that enables long term monitoring of cardiac rhythm. This device would utilise edge sensor technologies for dry, non-irritant skin contact suitable for distal limb application and would be supported by embedded ECG denoising processes. Contemporary ECG databases including those provided by MIT-BIH and Physionet are focused on interpretation of cardiac disease and rhythm tracking. The data is recorded using chest leads as in standard clinical practise. For the development of a peripherally located heart rhythm monitor, such data would be of limited use. To provide a useful database adequate for the development of the above mentioned cardiac monitoring device a unipolar body surface potential map from the left arm and wrist was gathered in 37 volunteer patients and characterized in this study. For this, the reference electrode was placed at the wrist. Bipolar far-field electrogram leads were derived and analysed. Factors such as skin variability, 50Hz noise interference, electrode contact noise, motion artifacts and electromyographic noise, presented a challenge. The objective was quantify the signal-to-noise ratio (SNR) at the far-field locations. Preliminary results reveal that an electrogram indicative of the QRS complex can be recorded on the distal portion of the left arm when denoised using signal averaging techniques.

  5. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  6. Oral hygiene teaching in clinical activities at the department of ...

    African Journals Online (AJOL)

    The aim of this study was to assess the attitudes and practices of students related to oral hygiene teaching by mean of a questionnaire submitted to patients attending the clinics of the Department of Dentistry of Dakar. Method: A KPC study (Knowledge, Practices and Coverage) focusing on dental students was conducted ...

  7. Learning from clinical placement experience: Analysing nursing students' final reflections in a digital storytelling activity.

    Science.gov (United States)

    Paliadelis, Penny; Wood, Pamela

    2016-09-01

    This paper reports on the learning potential of a reflective activity undertaken by final year nursing students, in which they were asked to recount two meaningful events that occurred during their clinical placements over the duration of their 3-year nursing degree program and reflect on how these events contributed to their learning to become beginning level Registered Nurses (RNs). This descriptive qualitative study gathered narratives from 92 students as individual postings in an online forum created within the University's learning management system. An analysis of the students' reflections are the focus of this paper particularly in relation to the value of reflecting on the identified events. Four themes emerged that clearly highlight the way in which these students interpreted and learned from both positive and negative clinical experiences, their strong desire to fit into their new role and their ability to re-imagine how they might respond to clinical events when they become Registered Nurses. The findings of this study may contribute to developing nursing curricula that better prepares final year students for the realities of practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Activity and potential role of licofelone in the management of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Arrigo FG Cicero

    2007-04-01

    Full Text Available Arrigo FG Cicero, Luca Laghi“D. Campanacci” Clinical Medicine & Applied Biotechnology Dept. Sant’Orsola-Malpighi Hospital – University of Bologna Via Massarenti, 9, 40138 Bologna, ItalyAbstract: Osteoarthritis is the most common form of arthritis. It is a progressive joint disease associated with aging. It may be found in the knees, hips, or other joints. It is estimated that costs associated with osteoarthritis exceed 2% of the gross national product in developed countries. Nonsteroidal anti-inflammatory drugs (NSAIDs are a mainstay in the treatment of inflammatory disease and are among the most widely used drugs worldwide. The main limitation in using NSAIDs consists in their side-effects, including gastrointestinal ulcerogenic activity and bronchospasm. The mechanism of action of these drugs is attributed to the inhibition of cyclooxygenase (COX, and, consequently, the conversion of arachidonic acid into prostaglandins. It is hypothesized that the undesirable side-effects of NSAIDs are due to the inhibition of COX-1 (constitutive isoform, whereas the beneficial effects are related to the inhibition of COX-2 (inducible isoform. Arachidonic acid can also be converted to leukotrienes (LTs by the action of 5-lipoxygenase (5-LOX. Licofelone, a LOX/COX competitive inhibitor, decreases the production of proinflammatory leukotrienes and prostaglandins (which are involved in the pathophysiology of osteoarthritis and in gastrointestinal (GI damage induced by NSAIDs and has the potential to combine good analgesic and anti-inflammatory effects with excellent GI tolerability. Preliminary data with this drug seem promising, but further well-designed clinical trials of this agent in the elderly will be necessary before a final evaluation is possible.Keywords: LOX/COX inhibitor, Licofelone, leukotrienes, osteoarthritis, nonsteroidal anti-inflammatory drugs

  9. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    Science.gov (United States)

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  10. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Directory of Open Access Journals (Sweden)

    Marcus May

    Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

  11. Phospholipase Activities in Clinical and Environmental Isolates of Acanthamoeba

    Science.gov (United States)

    Matin, Abdul

    2011-01-01

    The pathogenesis and pathophysiology of Acanthamoeba infections remain incompletely understood. Phos-pholipases are known to cleave phospholipids, suggesting their possible involvement in the host cell plasma membrane disruption leading to host cell penetration and lysis. The aims of the present study were to determine phospholipase activities in Acanthamoeba and to determine their roles in the pathogenesis of Acanthamoeba. Using an encephalitis isolate (T1 genotype), a keratitis isolate (T4 genotype), and an environmental isolate (T7 genotype), we demonstrated that Acanthamoeba exhibited phospholipase A2 (PLA2) and phospholipase D (PLD) activities in a spectrophotometry-based assay. Interestingly, the encephalitis isolates of Acanthamoeba exhibited higher phospholipase activities as compared with the keratitis isolates, but the environmental isolates exhibited the highest phospholipase activities. Moreover, Acanthamoeba isolates exhibited higher PLD activities compared with the PLA2. Acanthamoeba exhibited optimal phospholipase activities at 37℃ and at neutral pH indicating their physiological relevance. The functional role of phospholipases was determined by in vitro assays using human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. We observed that a PLD-specific inhibitor, i.e., compound 48/80, partially inhibited Acanthamoeba encephalitis isolate cytotoxicity of the host cells, while PLA2-specific inhibitor, i.e., cytidine 5'-diphosphocholine, had no effect on parasite-mediated HBMEC cytotoxicity. Overall, the T7 exhibited higher phospholipase activities as compared to the T4. In contract, the T7 exhibited minimal binding to, or cytotoxicity of, HBMEC. PMID:21461262

  12. Olive Oil-related Anti-inflammatory Effects on Atherosclerosis: Potential Clinical Implications.

    Science.gov (United States)

    Wongwarawipat, Tanakal; Papageorgiou, Nikolaos; Bertsias, Dimitrios; Siasos, Gerasimos; Tousoulis, Dimitris

    2018-01-01

    overcome these challenges to further assess the health benefits of EVOO consumption and potentially translate it into clinical practice as primary or secondary prevention of atherosclerosis-related conditions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Rett syndrome: establishing a novel outcome measure for walking activity in an era of clinical trials for rare disorders.

    Science.gov (United States)

    Downs, Jenny; Leonard, Helen; Jacoby, Peter; Brisco, Lauren; Baikie, Gordon; Hill, Kylie

    2015-01-01

    Rett syndrome is a pervasive neurological disorder with impaired gait as one criterion. This study investigated the capacity of three accelerometer-type devices to measure walking activity in Rett syndrome. Twenty-six participants (mean 18 years, SD 8) wore an Actigraph, ActivPAL and StepWatch Activity Monitor (SAM) during a video-taped session of activities. Agreement was determined between step-counts derived from each accelerometer and observation. Repeatability of SAM-derived step counts was determined using pairs of one-minute epochs during which the same participant was observed to walk with the same cadence. The mean difference (limit of agreement) for the Actigraph, ActivPAL and SAM were -41 (SD 33), -16 (SD 21) and -1 (SD 16) steps/min, respectively. Agreement was influenced by a device/cadence interaction (p Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials. Implications for Rehabilitation Many girls and women with Rett syndrome are able to walk on their own or with assistance but with altered movement patterns. Validated measures of physical activity, such as step counts, have potential to monitor function during daily life. Compared with other forms of accelerometer-type devices, such as ActiGraph and ActivPAL, the StepWatch Activity Monitor (SAM) measured step counts with good accuracy and repeatability. The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials.

  14. Developing Clinical Competency in Crisis Event Management: An Integrated Simulation Problem-Based Learning Activity

    Science.gov (United States)

    Liaw, S. Y.; Chen, F. G.; Klainin, P.; Brammer, J.; O'Brien, A.; Samarasekera, D. D.

    2010-01-01

    This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session…

  15. Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

    Science.gov (United States)

    Neville, Andrew J.; Zach, Sydney J.; Wang, Xiaofang; Larson, Joshua J.; Judge, Abigail K.; Davis, Lisa A.; Vennerstrom, Jonathan L.

    2015-01-01

    Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts. PMID:26392504

  16. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L......-phenylalanine nor L-serine methyl ester, stimulate insulin secretion. In the presence of L-glutamine, however, the effect of L-serine was additive, while the methyl esters of L-serine and L-phenylalanine as well as native L-phenylalanine, potentiated the glucose-stimulated release of insulin. Measurements of islet...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

  17. Ocular vestibular-evoked myogenic potentials (oVEMPs) require extraocular muscles but not facial or cochlear nerve activity.

    Science.gov (United States)

    Chihara, Yasuhiro; Iwasaki, Shinichi; Ushio, Munetaka; Fujimoto, Chisato; Kashio, Akinori; Kondo, Kenji; Ito, Ken; Asakage, Takahiro; Yamasoba, Tatsuya; Kaga, Kimitaka; Murofushi, Toshihisa

    2009-03-01

    Cervical vestibular evoked myogenic potentials (cVEMPs) have been found to be useful for clinical testing of vestibular function. Recently, investigators showed that short-latency, initially negative surface EMG potentials can be recorded around the extraocular muscles (oVEMPs) in response to air-conducted sound (ACS), bone-conducted vibration (BCV), and head taps. Although these evoked potentials, which are located around the eyes, most likely originate primarily from the otolith-ocular pathway, the possibility of contamination by other nerve activities cannot be completely eliminated. The purpose of the present study was to clarify the origin of oVEMPs by examining these possibilities using clinical findings. Twelve healthy subjects and 15 patients were enrolled. Of the 15 patients, 3 patients had undergone exenteration of the unilateral intraorbital contents, one had undergone exenteration of the right eyeball with preservation of extraocular muscles, 5 had facial palsy, and 6 had profound hearing loss. ACS and/or BCV were used in these subjects. Exenteration of the unilateral intraorbital contents resulted in absence of myogenic potentials on the affected side. On the other hand, exenteration of the eyeball with preservation of extraocular muscles did not have a major impact on the responses. There were no significant differences in the waveforms between healthy subjects and patients with facial palsy or profound hearing loss. The results suggested that short-latency, initially negative evoked potentials recorded below the eyes are not affected by cochlear or facial nerve activities and are dependent on the presence of extraocular muscles. This study provides the evidence that oVEMPs originate from exraocular muscles activated through the vestibulo-ocular pathway.

  18. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

    2016-01-01

    in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  19. Teachers' Views On The Potential Use Of Online 
In-Service Education And Training Activities

    OpenAIRE

    KOKOC, Mehmet; OZLU, Ayşenur; CIMER, Atilla; KARAL, Hasan

    2011-01-01

    This study examined teacher’s views on the potential use of online in-service education and training (INSET) activities. The study used a qualitative approach. A total of 13 in-service teachers from primary school, vocational school, science and art center, high school in Trabzon (on the Black Sea coast of Turkey) participated in the study. To determine opinions of participants about the potential use of online INSET activities, a online conference was held to determine teachers’ views. The p...

  20. Influence of membrane potential on conductance sublevels of chloride channels activated by GABA.

    Science.gov (United States)

    Gage, P W; Chung, S H

    1994-02-22

    Single-channel chloride currents activated by 0.5 microM GABA were recorded in cell-attached and inside-out membrane patches from rat cultured hippocampal neurons. The currents displayed multiple conductance states and outward rectification. The number and amplitude of conductance levels were determined over a range of potentials by using digital signal-processing techniques. It was found that, except for a level close to zero, subconductance levels were regularly spaced. There were fewer sublevels at hyperpolarized than at depolarized potentials, and the spacing between levels varied linearly with potential giving an incremental conductance of 8-10 pS that was independent of membrane potential. Outward rectification is related to the change in the number of conductance levels with potential. One hypothesis that is consistent with these observations is that a channel is composed of a number of synchronized, non-rectifying, conducting pores, and that the number of pores activated changes with membrane potential.

  1. Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

    Directory of Open Access Journals (Sweden)

    Maria Wideł

    2009-08-01

    Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

  2. The effects of water potential on some active forms of phosphorus in ...

    African Journals Online (AJOL)

    Immobilization and mobilization reactions of soil phosphorus depend on biological properties of soil and these soil properties strongly depend on the soil water potential. The objective of this study was to test the effects of water potential on some active forms of soil P. A semiarid soil classified as Calcic Haploxerept was ...

  3. Interlaced X-ray Microplanar Beams: A Radiosurgery Approach with Clinical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Dilimanian,F.; Zhong, Z.; Bacarian, T.; Benveniste, H.; Romanelli, P.; Wang, R.; Welwart, J.; Yuasa, T.; Rosen, E.; Anschel, D.

    2006-01-01

    Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25- to 90-{micro}m thick and spaced 100-300 {micro}m on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90 deg angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 x 3.4 x 3.4 mm3 exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120- and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-{micro}{micro}m dose falloff (80-20%) at the edge of the target, which is much less than the 2- to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.

  4. Interlaced X-ray Microplanar Beams: A Radiosurgery Approach with Clinical Potential

    International Nuclear Information System (INIS)

    Dilimanian, F.; Zhong, Z.; Bacarian, T.; Benveniste, H.; Romanelli, P.; Wang, R.; Welwart, J.; Yuasa, T.; Rosen, E.; Anschel, D.

    2006-01-01

    Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25- to 90-(micro)m thick and spaced 100-300 (micro)m on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90 deg angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 x 3.4 x 3.4 mm3 exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120- and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-(micro)(micro)m dose falloff (80-20%) at the edge of the target, which is much less than the 2- to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue

  5. Clinical utility and limitations of intraoperative monitoring of visual evoked potentials.

    Science.gov (United States)

    Luo, Yeda; Regli, Luca; Bozinov, Oliver; Sarnthein, Johannes

    2015-01-01

    During surgeries that put the visual pathway at risk of injury, continuous monitoring of the visual function is desirable. However, the intraoperative monitoring of the visual evoked potential (VEP) is not yet widely used. We evaluate here the clinical utility of intraoperative VEP monitoring. We analyzed retrospectively 46 consecutive surgeries in 2011-2013. High luminance stimulating devices delivered flash stimuli on the closed eyelid during intravenous anesthesia. We monitored VEP features N75 and P100 and took patients' preoperative and postoperative visual function from patient charts. Postoperative ophthalmologic workup was performed in 25 (54%) patients and preoperatively in 28 (61%) patients. VEP recordings were feasible in 62 of 85 eyes (73%) in 46 patients. All 23 eyes without VEP had impaired vision. During surgery, VEPs remained stable throughout surgery in 50 eyes. In 44 of these, visual function did not deteriorate and three patients (6 eyes) developed hemianopia. VEP decreased transiently in 10 eyes and visual function of all was preserved. VEPs were lost permanently in 2 eyes in two patients without new postoperative visual impairment. Satisfactory intraoperative VEP monitoring was feasible in all patients except in those with severe visual impairment. Preservation of VEPs predicted preserved visual function. During resection of lesions in the visual cortex, VEP monitoring could not detect new major visual field defects due to injury in the posterior visual pathway. Intraoperative VEPs were sensitive enough to detect vascular damage during aneurysm clipping and mechanical manipulation of the anterior visual pathway in an early reversible stage. Intraoperative VEP monitoring influenced surgical decisions in selected patients and proved to be a useful supplement to the toolbox of intraoperative neurophysiological monitoring.

  6. Clinical utility and limitations of intraoperative monitoring of visual evoked potentials.

    Directory of Open Access Journals (Sweden)

    Yeda Luo

    Full Text Available During surgeries that put the visual pathway at risk of injury, continuous monitoring of the visual function is desirable. However, the intraoperative monitoring of the visual evoked potential (VEP is not yet widely used. We evaluate here the clinical utility of intraoperative VEP monitoring.We analyzed retrospectively 46 consecutive surgeries in 2011-2013. High luminance stimulating devices delivered flash stimuli on the closed eyelid during intravenous anesthesia. We monitored VEP features N75 and P100 and took patients' preoperative and postoperative visual function from patient charts. Postoperative ophthalmologic workup was performed in 25 (54% patients and preoperatively in 28 (61% patients.VEP recordings were feasible in 62 of 85 eyes (73% in 46 patients. All 23 eyes without VEP had impaired vision. During surgery, VEPs remained stable throughout surgery in 50 eyes. In 44 of these, visual function did not deteriorate and three patients (6 eyes developed hemianopia. VEP decreased transiently in 10 eyes and visual function of all was preserved. VEPs were lost permanently in 2 eyes in two patients without new postoperative visual impairment.Satisfactory intraoperative VEP monitoring was feasible in all patients except in those with severe visual impairment. Preservation of VEPs predicted preserved visual function. During resection of lesions in the visual cortex, VEP monitoring could not detect new major visual field defects due to injury in the posterior visual pathway. Intraoperative VEPs were sensitive enough to detect vascular damage during aneurysm clipping and mechanical manipulation of the anterior visual pathway in an early reversible stage. Intraoperative VEP monitoring influenced surgical decisions in selected patients and proved to be a useful supplement to the toolbox of intraoperative neurophysiological monitoring.

  7. Active components and clinical applications of olive oil.

    Science.gov (United States)

    Waterman, Emily; Lockwood, Brian

    2007-12-01

    The olive tree, Olea europaea, is native to the Mediterranean basin and parts of Asia Minor. The fruit and compression-extracted oil have a wide range of therapeutic and culinary applications. Olive oil also constitutes a major component of the "Mediterranean diet." The chief active components of olive oil include oleic acid, phenolic constituents, and squalene. The main phenolics include hydroxytyrosol, tyrosol, and oleuropein, which occur in highest levels in virgin olive oil and have demonstrated antioxidant activity. Antioxidants are believed to be responsible for a number of olive oil's biological activities. Oleic acid, a monounsaturated fatty acid, has shown activity in cancer prevention, while squalene has also been identified as having anticancer effects. Olive oil consumption has benefit for colon and breast cancer prevention. The oil has been widely studied for its effects on coronary heart disease (CHD), specifically for its ability to reduce blood pressure and low-density lipoprotein (LDL) cholesterol. Antimicrobial activity of hydroxytyrosol, tyrosol, and oleuropein has been demonstrated against several strains of bacteria implicated in intestinal and respiratory infections. Although the majority of research has been conducted on the oil, consumption of whole olives might also confer health benefits.

  8. Can the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) be used to accurately report clinic total reproductive potential (TRP)?

    Science.gov (United States)

    Stern, Judy E; Hickman, Timothy N; Kinzer, Donna; Penzias, Alan S; Ball, G David; Gibbons, William E

    2012-04-01

    To assess whether total reproductive potential (TRP), the chance of a live birth from each fresh cycle (fresh cycle plus frozen transfers), could be calculated from the national Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database and whether information not available in SART CORS resulted in significant changes to the TRP calculation. Retrospective study using SART CORS and clinic data. Three assisted reproductive technology clinics. Women undergoing ART. None. Two- and three-year TRPs for 2005 and 2006 were calculated according to patient age at cycle start by linking fresh to frozen cycles up to first live birth. Clinic records were used to adjust for (remove) frozen cycles that used more than one fresh cycle as a source of embryos and for any embryos donated to other patients or research or shipped to another facility before a live birth. TRP was higher than fresh per-cycle rates for most ages at all clinics, although accuracy was compromised when there were fewer than 20 cycles per category. Two- and 3-year TRPs differed in only 2 of 24 calculations. Adjusted TRPs differed less than three percentage points from unadjusted TRPs when volume was sufficient. Clinic TRP can be calculated from SART CORS. Data suggest that calculations of clinic TRP from the national dataset would be meaningful. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

    Directory of Open Access Journals (Sweden)

    Bekdemir Yunus

    2008-08-01

    Full Text Available Abstract Background Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance. Methods Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested. Results The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably. Conclusion This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.

  10. Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival.

    Science.gov (United States)

    Maleux, Geert; Deroose, Christophe; Laenen, Annouschka; Verslype, Chris; Heye, Sam; Haustermans, Karin; De Hertogh, Gert; Sagaert, Xavier; Topal, Baki; Aerts, Raymond; Prenen, Hans; Vanbeckevoort, Dirk; Vandecaveye, Vincent; Van Cutsem, Eric

    2016-01-01

    The purpose of this study was to retrospectively assess the technical and clinical outcomes, overall survival and prognostic factors for prolonged survival after yttrium-90 ((90)Y) radioembolization as a salvage therapy for patients with chemorefractory liver-only or liver-dominant colorectal metastases. From January 2005 to January 2014, all the patients selected for (90)Y radioembolization to treat chemorefractory colorectal liver metastases were identified. Demographic, laboratory, imaging and dosimetry data were collected. Post-treatment technical and clinical outcomes were analyzed as well as overall survival; finally several factors potentially influencing survival were analyzed. In total 88 patients were selected for angiographic workup; 71 patients (81%) finally underwent catheter-directed (90)Y microsphere infusion into the hepatic artery 25 days (standard deviation 13 days) after angiographic workup. Median infused activity was 1809 MBq; 30-day toxicity included: fatigue (n = 39; 55%), abdominal discomfort (n = 33; 47%), nausea (n = 5; 7%), fever (n = 14; 20%), diarrhea (n = 6; 9%), liver function abnormalities and elevated bilirubin (transient) (n = 3; 4%). Gastric ulcer was found in five patients (7%). A late complication was radioembolization-induced portal hypertension (REIPH) in three patients (4%). Median time to progression in the liver was 4.4 months. Estimated survival at six and 12 months was 65% and 30%, respectively, with a 50% estimated survival after 8.0 months in this group of chemorefractory patients. Prognostic factors for worse survival were high preprocedural bilirubin, alkaline phosphatase and tumor volume levels. (90)Y microsphere radioembolization for chemorefractory colorectal liver metastases has an acceptable safety profile with a 50% estimated survival after 8.0 months. Pretreatment high bilirubin, alkaline phosphatase and tumor volume levels were associated with early death.

  11. Active compounds from cyanobacteria and microalgae: properties and potential applications in biomedicine

    Directory of Open Access Journals (Sweden)

    Alexey Llopiz

    2016-05-01

    Full Text Available Cyanobacteria and microalgae are source of many chemicals substances with potential applications on biopharmaceutical industry. Many structures have been characterized in these organism, such as: peptides, proteins, carbohydrates, terpenoids, polyinsatured fatty acids, flavonoids, phenolic compounds, vitamins, porfirins and other organic substances. Chemicals structures of isolated compounds are diverse and it depends of microalgae habitats. Pharmacological activities located in microalgae are bactericides, immunomodulatory, antioxidants, cytoprotective, fungicides and antivirals. These properties may possible the potential treatment of many diseases including autoimmunes disorders, tumoral, and infectious process. In this review are presented and discussed some elements associated to chemical structure and biological activities around of compounds with potential uses as biopharmaceuticals.

  12. Immuno-Detection of C3a, a C3 Complement Activated Product in Mastitis Milk, a Potential Diagnostic Marker.

    Science.gov (United States)

    Jacob, Thanislass; Subramani, Gangasudan; Sivaprakasam, Prathiba; Xavier, Antony P; Mukhopadhyay, Hirak K

    2017-02-23

    The sub-clinical form of mastitis is difficult to detect and causes huge economic loss to the dairy industry. It has become a threat to public health at large, thus there is a need for definite diagnosis of the disease. Therefore, this study was undertaken to identify the novel diagnostic marker for the detection of the sub-clinical form of mastitis. Two-dimensional gel analysis of the whey protein fraction of normal and mastitis milk samples revealed the presence of proteose peptone component 3 precursor, Trypsin precursor, complement component-C3, Ig heavy chain precursors and a C-type lectin domain as differentially expressed protein during the early stage of mastitis. Of these proteins identified, complement component-C3 was tested for its diagnostic potential. Western blot analysis of the milk whey of sub-clinical mastitis cases (M+, M++ & M+++) identified the accumulation of C3a, an activated product of complement component-C3. Further, the hemolytic activity of the above milk whey samples positively correlated with the somatic cell count. As C3a is already reported as an anaphylotoxic agent, it chemo tactically attracts lymphocytes at the site of inflammation, the detection of which in the milk whey can be of diagnostic importance for sub-clinical mastitis.

  13. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    2016-10-01

    Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

  14. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Science.gov (United States)

    Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

    2016-01-01

    Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

  15. Interrelationship among physical activity, quality of life, clinical and ...

    African Journals Online (AJOL)

    USER

    SUMMARY. A number of complexities surround the health and well-being of patients with type 2 diabetes. These difficulties relate to self-care efforts and outcomes, and several other factors play regulatory functions. This study was carried out to investigate the inter-relationship among physical activity, quality of life, and ...

  16. Detection of efflux pump activity among clinical isolates of ...

    African Journals Online (AJOL)

    Purpose: To detect efflux pump activity (EPA) and screening a suspected efflux pump inhibitor (EPI) [1- (3-(trifluoromethyl)benzyl]-piperazine (TFMBP)], which could help in reducing multi-drug resistance (MDR). Methods: Eighteen isolates, viz, 14 S. aureus, 2 S. lentus, 1 S. xylosus and 1 Micrococcus species from various ...

  17. Antibacterial activity of Eucalpytus citriodora Hk. oil on few clinically ...

    African Journals Online (AJOL)

    SERVER

    2008-01-04

    Jan 4, 2008 ... The antibacterial activity of Eucalyptus citriodora oil was evaluated. The volatile oil was extracted by steam distillation method. The tested bacterial strains were Escherichia coli ATCC 25922,. Staphylococcus aureus, Proteus mirabilis NCIM2241, Pseudomonas aeruginosa ATCC27853, Proteus vulgaris ...

  18. Predicting activities after stroke : what is clinically relevant?

    NARCIS (Netherlands)

    Kwakkel, G.; Kollen, B. J.

    Knowledge about factors that determine the final outcome after stroke is important for early stroke management, rehabilitation goals, and discharge planning. This narrative review provides an overview of current knowledge about the prediction of activities after stroke. We reviewed the pattern of

  19. Chemical potential in active systems: predicting phase equilibrium from bulk equations of state?

    Science.gov (United States)

    Paliwal, Siddharth; Rodenburg, Jeroen; van Roij, René; Dijkstra, Marjolein

    2018-01-01

    We derive a microscopic expression for a quantity μ that plays the role of chemical potential of active Brownian particles (ABPs) in a steady state in the absence of vortices. We show that μ consists of (i) an intrinsic chemical potential similar to passive systems, which depends on density and self-propulsion speed, but not on the external potential, (ii) the external potential, and (iii) a newly derived one-body swim potential due to the activity of the particles. Our simulations on ABPs show good agreement with our Fokker–Planck calculations, and confirm that μ (z) is spatially constant for several inhomogeneous active fluids in their steady states in a planar geometry. Finally, we show that phase coexistence of ABPs with a planar interface satisfies not only mechanical but also diffusive equilibrium. The coexistence can be well-described by equating the bulk chemical potential and bulk pressure obtained from bulk simulations for systems with low activity but requires explicit evaluation of the interfacial contributions at high activity.

  20. Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury

    Directory of Open Access Journals (Sweden)

    Ravirajsinh N. Jadeja

    2016-01-01

    Full Text Available Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2-related factor 2 (Nrf2, a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury. Several studies indicate that activation of Nrf2 signaling pathway ameliorates liver injury. The hepatoprotective potential of naturally occurring compounds has been investigated in various models of liver injuries. In this review, we comprehensively appraise various phytochemicals that have been assessed for their potential to halt acute and chronic liver injury by enhancing the activation of Nrf2 and have the potential for use in humans.

  1. Small-molecule inhibitors of SREBP activationpotential for new treatment of metabolic disorders

    OpenAIRE

    Watanabe, Mizuki; Uesugi, Motonari

    2013-01-01

    Sterol regulatory element-binding proteins (SREBPs) are transcriptional factors that control lipid and cholesterol metabolism. Activation of SREBPs in response to a decrease in cellular sterols results in acceleration of the synthesis of fatty acids, triglycerides, and cholesterol. Aberrant SREBP activity has been linked to metabolic disease states, such as obesity, fatty liver, insulin resistance, hyperlipidemia, and atherosclerosis. Thus, inhibition of SREBP activation is a potential therap...

  2. Applying a soft-robotic glove as assistive device and training tool with games to support hand function after stroke: Preliminary results on feasibility and potential clinical impact.

    Science.gov (United States)

    Prange-Lasonder, Gerdienke B; Radder, Bob; Kottink, Anke I R; Melendez-Calderon, Alejandro; Buurke, Jaap H; Rietman, Johan S

    2017-07-01

    Recent technological developments regarding wearable soft-robotic devices extend beyond the current application of rehabilitation robotics and enable unobtrusive support of the arms and hands during daily activities. In this light, the HandinMind (HiM) system was developed, comprising a soft-robotic, grip supporting glove with an added computer gaming environment. The present study aims to gain first insight into the feasibility of clinical application of the HiM system and its potential impact. In order to do so, both the direct influence of the HiM system on hand function as assistive device and its therapeutic potential, of either assistive or therapeutic use, were explored. A pilot randomized clinical trial was combined with a cross-sectional measurement (comparing performance with and without glove) at baseline in 5 chronic stroke patients, to investigate both the direct assistive and potential therapeutic effects of the HiM system. Extended use of the soft-robotic glove as assistive device at home or with dedicated gaming exercises in a clinical setting was applicable and feasible. A positive assistive effect of the soft-robotic glove was proposed for pinch strength and functional task performance 'lifting full cans' in most of the five participants. A potential therapeutic impact was suggested with predominantly improved hand strength in both participants with assistive use, and faster functional task performance in both participants with therapeutic application.

  3. A systematic review of intervention effects on potential mediators of children’s physical activity

    Directory of Open Access Journals (Sweden)

    Brown Helen

    2013-02-01

    Full Text Available Abstract Background Many interventions aiming to increase children’s physical activity have been developed and implemented in a variety of settings, and these interventions have previously been reviewed; however the focus of these reviews tends to be on the intervention effects on physical activity outcomes without consideration of the reasons and pathways leading to intervention success or otherwise. To systematically review the efficacy of physical activity interventions targeting 5-12 year old children on potential mediators and, where possible, to calculate the size of the intervention effect on the potential mediator. Methods A systematic search identified intervention studies that reported outcomes on potential mediators of physical activity among 5-12 year old children. Original research articles published between 1985 and April 2012 were reviewed. Results Eighteen potential mediators were identified from 31 studies. Positive effects on cognitive/psychological potential mediators were reported in 15 out of 31 studies. Positive effects on social environmental potential mediators were reported in three out of seven studies, and no effects on the physical environment were reported. Although no studies were identified that performed a mediating analysis, 33 positive intervention effects were found on targeted potential mediators (with effect sizes ranging from small to large and 73% of the time a positive effect on the physical activity outcome was reported. Conclusions Many studies have reported null intervention effects on potential mediators of children’s physical activity; however, it is important that intervention studies statistically examine the mediating effects of interventions so the most effective strategies can be implemented in future programs.

  4. The translational potential of human induced pluripotent stem cells for clinical neurology : The translational potential of hiPSCs in neurology.

    Science.gov (United States)

    Devine, Helen; Patani, Rickie

    2017-04-01

    The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies. This review will focus on the translational potential of hiPSCs in clinical neurology and the importance of integrating this approach with complementary model systems to increase the translational yield of preclinical testing for the benefit of patients. This strategy is particularly important given the expected increase in prevalence of neurodegenerative disease, which poses a major burden to global health over the coming decades.

  5. An Assessment of Six School-Based Clinics: Services, Impact and Potential.

    Science.gov (United States)

    Kirby, Douglas; And Others

    For two decades, school-based clinics have been providing basic health care to medically underserved teenagers and addressing the increasingly complex health and social problems facing young people, particularly unintended pregnancy. Today there are 150 school-based clinics operating in most major cities and many rural areas. In 1984, the Center…

  6. Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer.

    Science.gov (United States)

    Bao, Guo-Qing; Shen, Bai-Yong; Pan, Chun-Peng; Zhang, Ya-Jing; Shi, Min-Min; Peng, Cheng-Hong

    2013-09-12

    Gemcitabine is a first-line drug utilised in the chemotherapy of pancreatic cancer; however, this drug induces chemo-resistance and toxicity to normal tissue during treatment. Here, we firstly report that andrographolide (ANDRO) alone not only has anti-pancreatic cancer activity, but it also potentiates the anti-tumour activity of gemcitabine. Treatment with ANDRO alone inhibits proliferation of the pancreatic cancer cell lines in a dose- and time-dependent manner in vitro. Interestingly, ANDRO induces cell cycle arrest and apoptosis of pancreatic cancer cells by inhibiting STAT3 and Akt activation, upregulating the expression of p21(WAF1) and Bax, and downregulating the expression of cyclinD1, cyclinE, survivin, X-IAP and Bcl-2. Additionally, ANDRO combined with gemcitabine significantly induce stronger cell cycle arrest and more obvious apoptosis than each single treatment. The mechanistic study demonstrates that this synergistic effect is also dependent on the inhibition of STAT3 and Akt activations which subsequently regulates the pathways involved in the apoptosis and cell cycle arrest. Furthermore, both ANDRO alone and the combination treatments exhibit efficacious anti-tumour activity in vivo. Overall, our results provide solid evidence supporting that ANDRO alone or its combination with gemcitabine is a potential chemotherapeutic approach for treating human pancreatic cancer in clinical practice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Clinical potential, safety, and tolerability of arbaclofen in the treatment of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Frye RE

    2014-05-01

    Full Text Available Richard E FryeArkansas Children's Hospital Research Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USAAbstract: Autism spectrum disorder (ASD is a behaviorally defined disorder which has increased in prevalence over the last two decades. Despite decades of research, no effective treatment is currently available. Animal models, as well as other lines of evidence, point to abnormalities in the balance of cortical excitation to inhibition in individuals with ASD, with this imbalance resulting in an overall increase in cortical excitation. To reduce cortical excitatory glutamate pathways, arbaclofen, a selective agonist of the gamma aminobutyric acid receptor type B, has been developed. This article reviews the evidence for this treatment for ASD using a systematic review methodology. Overall, a systematic search of the literature revealed 148 relevant references with the majority of these being review papers or news items that mentioned the potential promise of arbaclofen. Five original studies were identified, four of which used STX209, a form of arbaclofen developed by Seaside Therapeutics, Inc., and one which used R-baclofen. In an animal model, treatment of Fragile X, a genetic disease with ASD features, demonstrated a reversal of behavioral, neurological, and neuropathological features associated with the disease. One double-blind, placebo-controlled study treated children and adults with Fragile X. Results from this study were promising, with signs of improvement in social function, especially in the most severely socially impaired. Two studies, one open-label and one double-blind, placebo-controlled, were conducted in children, adolescents, and young adults with ASD. These studies suggested some improvements in socialization, although the effects were limited and may have been driven by individuals with ASD that were higher-functioning. These studies and others that have used arbaclofen for

  8. Are potentially clinically meaningful benefits misinterpreted in cardiovascular randomized trials? A systematic examination of statistical significance, clinical significance, and authors' conclusions.

    Science.gov (United States)

    Allan, G Michael; Finley, Caitlin R; McCormack, James; Kumar, Vivek; Kwong, Simon; Braschi, Emelie; Korownyk, Christina; Kolber, Michael R; Lindblad, Adriennne J; Babenko, Oksana; Garrison, Scott

    2017-03-20

    While journals and reporting guidelines recommend the presentation of confidence intervals, many authors adhere strictly to statistically significant testing. Our objective was to determine what proportions of not statistically significant (NSS) cardiovascular trials include potentially clinically meaningful effects in primary outcomes and if these are associated with authors' conclusions. Cardiovascular studies published in six high-impact journals between 1 January 2010 and 31 December 2014 were identified via PubMed. Two independent reviewers selected trials with major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death) as primary outcomes and extracted data on trial characteristics, quality, and primary outcome. Potentially clinically meaningful effects were defined broadly as a relative risk point estimate ≤0.94 (based on the effects of ezetimibe) and/or a lower confidence interval ≤0.75 (based on the effects of statins). We identified 127 randomized trial comparisons from 3200 articles. The primary outcomes were statistically significant (SS) favoring treatment in 21% (27/127), NSS in 72% (92/127), and SS favoring control in 6% (8/127). In 61% of NSS trials (56/92), the point estimate and/or lower confidence interval included potentially meaningful effects. Both point estimate and confidence interval included potentially meaningful effects in 67% of trials (12/18) in which authors' concluded that treatment was superior, in 28% (16/58) with a neutral conclusion, and in 6% (1/16) in which authors' concluded that control was superior. In a sensitivity analysis, 26% of NSS trials would include potential meaningful effects with relative risk thresholds of point estimate ≤0.85 and/or a lower confidence interval ≤0.65. Point estimates and/or confidence intervals included potentially clinically meaningful effects in up to 61% of NSS cardiovascular trials. Authors' conclusions often reflect potentially meaningful results of

  9. Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

    Science.gov (United States)

    Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

    2018-01-01

    Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Clinical activity of pazopanib in metastatic extraosseous Ewing sarcoma

    Directory of Open Access Journals (Sweden)

    Steven Attia

    2015-05-01

    Full Text Available We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371. This national multi-institutional study is ongoing.

  11. TEACHERS' VIEWS ON THE POTENTIAL USE OF ONLINE IN-SERVICE EDUCATION AND TRAINING ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Mehmet KOKOC

    2011-10-01

    Full Text Available This study examined teacher’s views on the potential use of online in-service education and training (INSET activities. The study used a qualitative approach. A total of 13 in-service teachers from primary school, vocational school, science and art center, high school in Trabzon (on the Black Sea coast of Turkey participated in the study. To determine opinions of participants about the potential use of online INSET activities, a online conference was held to determine teachers’ views. The participants who had experienced traditional and face to face INSET courses discussed their INSET experiences and thoughts about online INSET activities. These views were transcribed and then analyzed using content analysis. The main conclusions are: with online INSET activities, especially time and place dependency can be overcome, and accommodation and transportation issues can be resolved. Teachers feel that online INSET activities can promote effective use of resources.

  12. In vitro antibacterial activity of onion (allium cepa) against clinical isolates of vibrio cholera

    International Nuclear Information System (INIS)

    Hannan, A.; Humayun, T.; Hussain, M.B.; Yasir, M.; Sikandar, S.

    2010-01-01

    Background: Cholera is a major public health problem in developing countries of the world. Bacterial resistance, lack of surveillance data and proper microbiological facilities are major problems regarding diagnosis of cholera. The spread of microbial drug resistance is a global public health challenge that results in increased illness and death rate. Newer antimicrobials or agents are urgently required to overcome this problem. This work was therefore done to investigate the antimicrobial potential of onion against thirty-three clinical isolates of Vibrio cholera. Methods: The extract was prepared by reflux extraction method. Antibacterial screening of clinical isolates of V. cholerae was done by agar well diffusion method. Agar dilution method was used to assess the Minimum Inhibitory Concentration (MIC). Results: All tested strains of V. cholerae were sensitive to onion (Allium cepa) extracts of two types (purple and yellow). Purple type of extract had MIC range of 19.2-21.6 mg/ml. The extract of yellow type onion had an MIC range of 66-68.4 mg/ml. Conclusion: The results indicated that onion (Allium cepa) has an inhibitory effect on V. cholerae. Keeping in view the anti-bacterial activity of this compound can be exploited as a therapeutic agent in an animal model. This finding is a positive point for further investigation of this herb of traditional medicine. (author)

  13. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    Science.gov (United States)

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  14. Quality of clinical supervision and counselor emotional exhaustion: the potential mediating roles of organizational and occupational commitment.

    Science.gov (United States)

    Knudsen, Hannah K; Roman, Paul M; Abraham, Amanda J

    2013-01-01

    Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse's Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria.

    Directory of Open Access Journals (Sweden)

    Divakara S S M Uppu

    Full Text Available Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells. The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

  16. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria.

    Science.gov (United States)

    Uppu, Divakara S S M; Konai, Mohini M; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C M; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R; Franco, Octávio L; Haldar, Jayanta

    2017-01-01

    Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

  17. Evaluating predictive modeling's potential to improve teleretinal screening participation in urban safety net clinics.

    Science.gov (United States)

    Ogunyemi, Omolola; Teklehaimanot, Senait; Patty, Lauren; Moran, Erin; George, Sheba

    2013-01-01

    Screening guidelines for diabetic patients recommend yearly eye examinations to detect diabetic retinopathy and other forms of diabetic eye disease. However, annual screening rates for retinopathy in US urban safety net settings remain low. Using data gathered from a study of teleretinal screening in six urban safety net clinics, we assessed whether predictive modeling could be of value in identifying patients at risk of developing retinopathy. We developed and examined the accuracy of two predictive modeling approaches for diabetic retinopathy in a sample of 513 diabetic individuals, using routinely available clinical variables from retrospective medical record reviews. Bayesian networks and radial basis function (neural) networks were learned using ten-fold cross-validation. The predictive models were modestly predictive with the best model having an AUC of 0.71. Using routinely available clinical variables to predict patients at risk of developing retinopathy and to target them for annual eye screenings may be of some usefulness to safety net clinics.

  18. Understanding the value added to clinical care by educational activities. Value of Education Research Group.

    Science.gov (United States)

    Ogrinc, G S; Headrick, L A; Boex, J R

    1999-10-01

    In an era of competition in health care delivery, those who pay for care are interested in supporting primarily those activities that add value to the clinical enterprise. The authors report on their 1998 project to develop a conceptual model for assessing the value added to clinical care by educational activities. Through interviews, nine key stakeholders in patient care identified five ways in which education might add value to clinical care: education can foster higher-quality care, improve work satisfaction of clinicians, have trainees provide direct clinical services, improve recruitment and retention of clinicians, and contribute to the future of health care. With this as a base, an expert panel of 13 clinical educators and investigators defined six perspectives from which the value of education in clinical care might be studied: the perspectives of health-care-oriented organizations, clinician-teachers, patients, education organizations, learners, and the community. The panel adapted an existing model to create the "Education Compass" to portray education's effects on clinical care, and developed a new set of definitions and research questions for each of the four major aspects of the model (clinical, functional, satisfaction, and cost). Working groups next drafted proposals to address empirically those questions, which were critiqued at a national conference on the topic of education's value in clinical care. The next step is to use the methods developed in this project to empirically assess the value added by educational activities to clinical care.

  19. The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

    Science.gov (United States)

    Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

    2014-07-01

    The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design

  20. Gallium nitrate: the second metal with clinical activity.

    Science.gov (United States)

    Foster, B J; Clagett-Carr, K; Hoth, D; Leyland-Jones, B

    1986-11-01

    Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the

  1. Clinical relevance of imaging proliferative activity in lung nodules

    Energy Technology Data Exchange (ETDEWEB)

    Buck, Andreas K.; Schirrmeister, Holger; Kratochwil, Clemens; Wahl, Andreas; Glatting, Gerhard; Mottaghy, Felix M.; Neumaier, Bernd; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Hetzel, Martin [University of Ulm, Department of Internal Medicine II - Pulmonary Medicine, Ulm (Germany); Halter, Gisela [University of Ulm, Department of Thoracic Surgery, Ulm (Germany); Moeller, Peter; Mattfeldt, Torsten [University of Ulm, Department of Pathology, Ulm (Germany)

    2005-04-01

    Recently, the thymidine analogue 3'-deoxy-3'[{sup 18}F]fluorothymidine (FLT) has been introduced for imaging proliferation with positron emission tomography (PET). In this prospective study, we examined the accuracy of FLT for differentiation of benign from malignant lung lesions and for tumour staging. A total of 47 patients with newly diagnosed pulmonary nodules on chest CT suspicious for malignancy were examined with FLT-PET in addition to routine staging procedures. A total of 43 patients also underwent 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) PET imaging. Within 2 weeks, patients underwent resective surgery or core biopsy of the pulmonary lesion. Histopathology revealed malignant lung tumours in 32 patients (20 non-small cell lung cancer, 1 small cell lung cancer, 1 pulmonary carcinoid, 1 non-Hodgkin's lymphoma, nine metastases from extrapulmonary tumours) and benign lesions in 15 patients. Increased FLT uptake was exclusively related to malignant tumours. FLT-PET was false negative in two patients with non-small cell lung cancer, in the patient with a pulmonary carcinoid and in three patients with lung metastases. The sensitivity of FLT-PET for detection of lung cancer was 90%, the specificity 100% and the accuracy 94%. Fifteen out of 21 patients with lung cancer had mediastinal lymph node metastases. FLT-PET was true positive in 7/15 patients, resulting in a sensitivity of 53% for N-staging (specificity 100%, accuracy 67%). Clinical TNM stage was correctly identified in 67% (20/30) patients, compared to 85% (23/27) with FDG-PET. FLT-PET has a high specificity for the detection of malignant lung tumours. Compared with FDG, FLT-PET is less accurate for N-staging in patients with lung cancer and for detection of lung metastases. FLT-PET therefore cannot be recommended for staging of lung cancer. (orig.)

  2. Influence of the Ambient Electric Field on Measurements of the Actively Controlled Spacecraft Potential by MMS

    Science.gov (United States)

    Torkar, K.; Nakamura, R.; Andriopoulou, M.; Giles, B. L.; Jeszenszky, H.; Khotyaintsev, Y. V.; Lindqvist, P.-A.; Torbert, R. B.

    2017-12-01

    Space missions with sophisticated plasma instrumentation such as Magnetospheric Multiscale, which employs four satellites to explore near-Earth space benefit from a low electric potential of the spacecraft, to improve the plasma measurements and therefore carry instruments to actively control the potential by means of ion beams. Without control, the potential varies in anticorrelation with plasma density and temperature to maintain an equilibrium between the plasma current and the one of photoelectrons produced at the surface and overcoming the potential barrier. A drawback of the controlled, almost constant potential is the difficulty to use it as convenient estimator for plasma density. This paper identifies a correlation between the spacecraft potential and the ambient electric field, both measured by double probes mounted at the end of wire booms, as the main responsible for artifacts in the potential data besides the known effect of the variable photoelectron production due to changing illumination of the surface. It is shown that the effect of density variations is too weak to explain the observed correlation with the electric field and that a correction of the artifacts can be achieved to enable the reconstruction of the uncontrolled potential and plasma density in turn. Two possible mechanisms are discussed: the asymmetry of the current-voltage characteristic determining the probe to plasma potential and the fact that a large equipotential structure embedded in an electric field results in asymmetries of both the emission and spatial distribution of photoelectrons, which results in an increase of the spacecraft potential.

  3. Event-related potential study of frontal activity during imagination of rhythm.

    Science.gov (United States)

    Jomori, Izumi; Uemura, Jun-ichi; Nakagawa, Yoshiro; Hoshiyama, Minoru

    2011-12-01

    In 11 healthy volunteers, we used event-related potentials (ERP) to investigate the frontal activity associated with imagining a beat. In imagery sessions, subjects were asked to imagine a rhythm during a silent recording period following a series of guide sounds played at 1 Hz. In control sessions, subjects were asked to imagine a vowel sound ("a") continuously during the silent recording period. In eight subjects, relative negative potentials were recorded during imagery sessions (compared with potentials in control sessions), with timing that was similar to that of the guide sounds. Activity in the left frontal region was more significant than that in other areas during beat imagination. These data indicate that a semantic strategy for simple rhythm imagery might involve temporary phasic activation in the left frontal area, although rhythm production and perception might be generated in the right side, as reported in previous studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Development of C-Methyl Branched Purine Ribonucleoside Analogs: Chemistry, Biological Activity and Therapeutic Potential.

    Science.gov (United States)

    Petrelli, Riccardo; Grifantini, Mario; Cappellacci, Loredana

    2016-01-01

    In this review, we first highlighted on C-methyl-branched nucleosides and nucleotides approved as anti-hepatitis C infection (HCV) drugs, their mechanism of action and recent progress in the development of new clinical candidates. Then, we report on our attempt to develop several C-methyl nucleosides/tides potentially useful for treatment of various diseases such cancer, pain, epilepsy and glaucoma. Design, synthesis and pharmacological screening of 1'-C-, 2'-C-, 3'-C-methyladenosine or other purine/pyrimidine nucleosides allowed us to discover some promising new molecules. 3'-C-Methyladenosine showed antitumor activity against several human tumor cell lines. We have investigated the mechanism of action of 3;-C-methyladenosine that proved to be an effective inhibitor of ribonucleotide reductase. Moreover, we will also summarize the chemical and biological properties of some of the recent N6-substituted and 5', N6-disubstituted 2'-C-methyladenosine derivatives that were synthetized in our laboratory and evaluated as A1 adenosine receptor agonists. 2-Chloro-2'- C-methyl-N6-cyclopentyladenosine (2'-Me-CCPA), 5'-chloro-5'-deoxy-N6-(±)-(endo-norborn- 2-yl)adenosine (5'Cl5'd-(±)-ENBA) and 2'-C-methyl-5'-chloro-5'-deoxy-N6-(±)-(endonorborn- 2-yl)adenosine (2'-Me-5'Cl5'd-(±)-ENBA) displayed high hA1AR affinity and selectivity. 2'-Me-CCPA and 5'Cl5'd-(±)-ENBA showed significant analgesic properties.

  5. Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity.

    Science.gov (United States)

    Stratigou, Victoria; Doyle, Anne F; Carlucci, Francesco; Stephens, Lauren; Foschi, Valentina; Castelli, Marco; McKenna, Nicola; Cook, H Terence; Lightstone, Liz; Cairns, Thomas D; Pickering, Matthew C; Botto, Marina

    2017-07-01

    The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  6. Robotic Arm-Assisted Sonography: Review of Technical Developments and Potential Clinical Applications.

    Science.gov (United States)

    Swerdlow, Daniel R; Cleary, Kevin; Wilson, Emmanuel; Azizi-Koutenaei, Bamshad; Monfaredi, Reza

    2017-04-01

    Ultrasound imaging requires trained personnel. Advances in robotics and data transmission create the possibility of telesonography. This review introduces clinicians to current technical work in and potential applications of this developing capability. Telesonography offers advantages in hazardous or remote environments. Robotically assisted ultrasound can reduce stress injuries in sonographers and has potential utility during robotic surgery and interventional procedures.

  7. Estrogenic activity and identification of potential xenoestrogens in a coking wastewater treatment plant.

    Science.gov (United States)

    Zhao, Jian-Liang; Chen, Xiao-Wen; Yan, Bo; Wei, Chaohai; Jiang, Yu-Xia; Ying, Guang-Guo

    2015-02-01

    In this study, the estrogenic activities in influent and effluents of coking wastewater from different treatment stages were studied using Yeast Estrogen Screen (YES) bioassays. Raw extracts were further fractioned to identify the potential xenoestrogens combined with YES bioassays and gas chromatography-mass spectrometry analysis. Influent, primary effluent, and anaerobic effluent showed high estrogenic activities, with potencies of 1136±269, 1417±320, and 959±69 ng/L of 17β-estradiol (E2) equivalent (EEQ), respectively. The potency of estrogenic activity was gradually removed through the treatment processes. In the final effluent, the estrogenic activity was reduced to 0.87 ng EEQ/L with a total removal efficiency of more than 99%, suggesting that the estrogenic activity was almost completely removed in the coking wastewater. For the fractions of raw extracts, bioassay results showed that the estrogenic activities were mostly present in the polar fractions. Correlation analysis between estrogenic activities and responses of identified chemicals indicated that potential xenoestrogens were the derivatives of indenol, naphthalenol, indol, acridinone, fluorenone, and carbazole. The estrogenic activity in the final effluent was higher than the predicted no effect concentration (PNEC) for E2, implying that the discharged effluent would probably exert estrogenic activity risk to the aquatic ecosystem in "the worst-case scenario." Copyright © 2014. Published by Elsevier Inc.

  8. In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus.

    Science.gov (United States)

    Narayanaswamy, Vidya P; Giatpaiboon, Scott A; Uhrig, John; Orwin, Paul; Wiesmann, William; Baker, Shenda M; Townsend, Stacy M

    2018-01-01

    The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections. This study demonstrates the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU) in ≤ 12-hours at doses that are non-toxic to mammalian cells. PAAG also sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by the observed reduction in the oxacillin MIC to below the antibiotic resistance breakpoint. The effect of PAAG and standard antibiotics including vancomycin, oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies showed that S. aureus developed resistance to PAAG at a rate slower than to mupirocin but similar to bacitracin. PAAG was observed to resensitize drug-resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage resistance study, reducing MICs of mupirocin and bacitracin below their clinical sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria.

  9. Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

    Science.gov (United States)

    Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

    2015-01-01

    Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

  10. Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity

    Science.gov (United States)

    Miyamoto, Yukiko; Kalisiak, Jarosław; Korthals, Keith; Lauwaet, Tineke; Cheung, Dae Young; Lozano, Ricardo; Cobo, Eduardo R.; Upcroft, Peter; Upcroft, Jacqueline A.; Berg, Douglas E.; Gillin, Frances D.; Fokin, Valery V.; Sharpless, K. Barry; Eckmann, Lars

    2013-01-01

    Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug class unexplored. Here we report on a unique approach to the modular synthesis of diversified 5-NIs for broad exploration of their antimicrobial potential. Many of the more than 650 synthesized compounds, carrying structurally diverse functional groups, have vastly improved activity against a range of microbes, including the pathogenic protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Furthermore, they can overcome different forms of drug resistance, and are active and nontoxic in animal infection models. These findings provide impetus to the development of structurally diverse, next-generation 5-NI drugs as agents in the antimicrobial armamentarium, thus ensuring their future viability as primary therapeutic agents against many clinically important infections. PMID:24101497

  11. Clinical implications of proteolytic activity imbalance in breast cancer diagnosis.

    Science.gov (United States)

    Swellam, Menha; Soliman, Hanan A; Abdelmaksoud, Mohamed D E; Nageeb, Amira M; El Arab, Lobna R Ezz; Boshnak, Hussein

    2014-01-01

    Matrix metalloproteinase-9 and its tissue inhibitor TIMP-1 have been documented as putative tumor markers because of their involvement in cancer invasion and metastasis. The aim of our study was to elucidate the diagnostic efficacy of proteolytic activity markers among traditional tumor markers (CEA and CA15.3) and clinicopathological variables. Serum samples were withdrawn from 160 individuals (80 patients with primary breast cancer, 40 patients with benign breast lesions and 40 individuals serve as healthy controls). MMP-9 and TIMP-1 were measured by ELISA and gelatin zymography. The best cutoff points for MMP-9 and TIMP-1 were depicted by receiver operating characteristic (ROC) curve. The positivity rates and the median levels for MMP-9 and TIMP-1 showed significant difference among the three investigated groups (Phormonal receptor status (ER, and PgR). MMP zymography results were comparable to those from ELISA. The sensitivity and the specificity of MMP-9, TIMP-1 and MMP-9/TIMP-1 were superior to traditional tumor markers (CEA and CA15.3) especially for early stages (T1) and low grade breast cancer patients. These findings indicate that investigated biomarkers are constructive for early diagnosis of breast cancer and MMP-9/TIMP-1 ratio might be a new significant marker in predicting breast cancer development.

  12. Motor activation SPECT for the neurosurgical diseases. Clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Noguchi, Hiroshi; Kawaguchi, Shoichiro; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime [Nara Medical Univ., Kashihara (Japan)

    1999-08-01

    We evaluated and analyzed the motor activation single photon emission computed tomography (M-SPECT) findings on patients with ischemic cerebrovascular diseases (CVD). The M-SPECT studies were carried out on 91 patients with ischemic cerebrovascular diseases. The M-SPECT study was performed using the finger opposition task in each case. The SPECT images were superimposed on the magnetic resonance images (MRIs) for each case using Image Fusion Software. The result of the M-SPECT was expressed as positive or negative. The cases with a marked increase of blood flow in the sensorio-motor cortex after the finger opposition task were categorized as positive, and those cases showing no marked increase of blood flow were categorized as negative. Among the 91 cases examined, 53 (58%) were categorized as positive in the M-SPECT study. Among the negative M-SPECT cases treated with revascularization surgery, there were some cases showing positive M-SPECT results postoperatively. The cases without any revascularization surgery did not change the M-SPECT findings in each during the follow-up period. The M-SPECT procedure for examining intracranial lesions could provide the cortical localization of the motor function. The M-SPECT procedure in the ischemic CVDs contributes to knowledge about the choices of treatment and the evaluation of the treatment result. (author)

  13. Emergence of Rare Species of Nontuberculous Mycobacteria as Potential Pathogens in Saudi Arabian Clinical Setting.

    Science.gov (United States)

    Varghese, Bright; Enani, Mushira; Shoukri, Mohammed; AlThawadi, Sahar; AlJohani, Sameera; Al-Hajoj, Sahal

    2017-01-01

    Clinical relevance of nontuberculous mycobacteria (NTM) is increasing worldwide including in Saudi Arabia. A high species diversity of NTM's has been noticed in a recent study. However, the identification in diagnostic laboratories is mostly limited to common species. The impact of NTM species diversity on clinical outcome is so far neglected in most of the clinical settings. During April 2014 to September 2015, a nationwide collection of suspected NTM clinical isolates with clinical and demographical data were carried out. Primary identification was performed by commercial line probe assays. Isolates identified up to Mycobacterium species level by line probe assays only were included and subjected to sequencing of 16S rRNA, rpoB, hsp65 and 16S-23S ITS region genes. The sequence data were subjected to BLAST analysis in GenBank and Ez-Taxon databases. Male Saudi nationals were dominated in the study population and falling majorly into the 46-59 years age group. Pulmonary cases were 59.3% with a surprising clinical relevance of 75% based on American Thoracic Society guidelines. Among the 40.7% extra-pulmonary cases, 50% of them were skin infections. The identification revealed 16 species and all of them are reporting for the first time in Saudi Arabia. The major species obtained were Mycobacterium monascence (18.5%), M. cosmeticum (11.1%), M. kubicae (11.1%), M. duvalli (7.4%), M.terrae (7.4%) and M. triplex (7.4%). This is the first report on clinical relevance of M. kubicae, M. tusciae, M.yongonense, M. arupense and M.iranicum causing pulmonary disease and M. monascence, M. duvalli, M. perigrinum, M. insubricum, M. holsaticum and M. kyorinense causing various extra-pulmonary diseases in Saudi Arabia. Ascites caused by M. monascence and cecum infection by M. holsaticum were the rarest incidents. To the first time in the country, clinical significance of various rare NTM's are well explored and the finding warrants a new threat to the Saudi Arabian clinical settings.

  14. Comparative study of genetic activity of chlorambucil's active metabolite steroidal esters: The role of steroidal skeleton on aneugenic potential

    International Nuclear Information System (INIS)

    Efthimiou, M.; Ouranou, D.; Stephanou, G.; Demopoulos, N.A.; Nikolaropoulos, S.S.; Alevizos, Ph.

    2010-01-01

    p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE), a nitrogen mustard analogue and chlorambucil's active metabolite used as chemotherapeutic agent, has been shown that, in addition to its clastogenic activity, induces chromosome delay. In the present study an efford has been made (a) to investigate if the steroidal analogues of PHE (EA-92, EA-97, AK-333, AK-409 and AK-433) exert the same genetic activity as the parent compound, (b) to further analyze the aneugenic activity of nitrogen mustard analogues, (c) to investigate the mechanism by which they exert aneugenic potential and (d) to correlate the genetic activity with chemical structure. For this purpose the Cytokinesis Block Micronucleus (CBMN) assay was conducted in human lymphocytes in vitro and the micronucleus (MN) frequency was determined to investigate their genetic activity. The mechanism of micronucleation was determined in combination with Fluorescence In Situ Hybridization (FISH) using pancentromeric DNA probe. Since one of the mechanisms that chemicals cause aneuploidy is through alterations in the mitotic spindle, we also investigated the effect of the above compounds on the integrity and morphology of the mitotic spindle using double immunofluorescence of β- and γ-tubulin in C 2 C 12 mouse cell line. We found that PHE and its steroidal analogues, EA-92, EA-97, AK-333, AK-409 and AK-433, affect cell proliferation in human lymphocytes and C 2 C 12 mouse cells. All studied compounds are capable of inducing chromosome breakage events, as indicated by the enhanced C - MN frequencies. The less lipophilic compounds are the most genetically active molecules. PHE and only two of the studied analogues, AK-409 and AK-433, the most hydrophilic ones, showed aneugenic potential, by increasing the frequencies of MN containing a whole chromosome. The aneugenic potential of the above referred analogues is associated with amplification of centrosome number, since they caused high multipolar metaphase

  15. Spatial distribution of non-clinical Rift Valley fever viral activity in ...

    African Journals Online (AJOL)

    Rift Valley fever (RVF) is an acute zoonotic viral disease of domestic ruminants in mainland Africa and Madagascar. The disease may exist in non-clinical form in apparently health animals. This study was designed to investigate the existence and spatial distribution of non-clinical form of RVF virus (RVFV) activity in wild and ...

  16. Analysis of Potential Drug-Drug Interactions and Its Clinical Manifestation of Pediatric Prescription on 2 Pharmacies in Bandung

    Directory of Open Access Journals (Sweden)

    Melisa I. Barliana

    2013-09-01

    Full Text Available The potential of Drug-Drug Interactions (DDI in prescription have high incidence around the world, including Indonesia. However, scientific evidence regarding DDI in Indonesia is not available. Therefore, in this study we have conducted survey in 2 pharmacies in Bandung against pediatric prescription given by pediatrician. These prescriptions then analyzed the potential for DDI contained in the prescription and clinical manifestation. The analysis showed that in pharmacy A, there are 33 prescriptions (from a total of 155 prescriptions that have potential DDI, or approximately 21.19% (2 prescriptions have the potential DDI major categories, 23 prescriptions categorized as moderate, and 8 prescriptions as minor. In Pharmacy B, there are 6 prescriptions (from a total of 40 prescriptions or 15% of potential DDI (4 prescriptions categorized as moderate and 2 prescriptions as minor. This result showed that potential DDI happened less than 50% in pediatric prescription from both pharmacies. However, this should get attention because DDI should not happen in a prescription considering its clinical manifestations caused by DDI. Moreover, current pharmaceutical care refers to patient oriented than product oriented. In addition, further study for the pediatric prescription on DDI incidence in large scale need to be investigated.

  17. Molluscicidal hydroxynaphthoquinones and derivatives: correlation between their redox potentials and activity against Biomphalaria glabrata

    Directory of Open Access Journals (Sweden)

    Lima Nadja M. F.

    2002-01-01

    Full Text Available Several 2-hydroxy-3-alkyl-1,4-naphthoquinones have been submitted to molluscicidal bioassays against the snail Biomphalaria glabrata, intermediate host of Schistosoma mansoni. Cyclic voltammetric studies in aprotic medium (N,N-dimethylformamide plus tetrabutylammonium perchlorate on Hg and glassy carbon electrodes have been performed on these compounds in order to obtain information about their biological mechanism of action. Several of the quinones assayed showed significant molluscicidal activities, and correlation of their activities and electrochemical parameters showed that the first wave reduction potential is an important parameter. The easily reduced quinones (>Ep1c were more active against adult snails and against their egg masses, whilst the 3-methylamino-2-hydroxy derivatives presented higher negative reduction potentials and were not active as molluscicides.

  18. Determination of Carboxypeptidase Activity in Clinical Pathogens by Gas Chromatography?Mass Spectrometry

    OpenAIRE

    Lough, Fraser; Perry, John D.; Stanforth, Stephen P.; Dean, John R.

    2016-01-01

    ABSTRACT A novel method for the determination of benzoic acid has been employed to identify carboxypeptidase activities in clinically relevant pathogens. Benzoic acid was determined after chemical derivatization by gas chromatography?mass spectrometry (GC?MS). N-Benzoyl amino acid substrates were evaluated for the detection of carboxypeptidase activities in a number of clinical pathogens. Upon enzymatic hydrolysis of these substrates, benzoic acid was produced which was detected by extraction...

  19. Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System.

    Science.gov (United States)

    Poole, Keith; Gilmour, Christie; Farha, Maya A; Mullen, Erin; Lau, Calvin Ho-Fung; Brown, Eric D

    2016-06-01

    A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS undermining mexXY expression and its promotion of resistance to 4,5- and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment of P. aeruginosa infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Functional characterization of brain tumors: An overview of the potential clinical value

    Energy Technology Data Exchange (ETDEWEB)

    Brunetti, Arturo; Alfano, Bruno; Soricelli, Andrea; Tedeschi, Enrico; Mainolfi, Ciro; Covelli, Eugenio M.; Aloj, Luigi; Panico, Maria Rosaria; Bazzicalupo, Lucio; Salvatore, Marco

    1996-08-01

    Early detection and characterization are still challenging issues in the diagnostic approach to brain tumors. Among functional imaging techniques, a clinical role for positron emission tomography studies with [{sup 18}F]-fluorodeoxyglucose and for single photon emission computed tomography studies with [{sup 201}Tl]-thallium-chloride has emerged. The clinical role of magnetic resonance spectroscopy is still being defined, whereas functional magnetic resonance imaging seems able to provide useful data for presurgical localization of critical cortical areas. Integration of morphostructural information provided by computed tomography and magnetic resonance imaging, with functional characterization and cyto-histologic evaluation of biologic markers, may assist in answering the open diagnostic questions concerning brain tumors.

  1. Potential cost-effectiveness of a new infant tuberculosis vaccine in South Africa--implications for clinical trials: a decision analysis.

    Directory of Open Access Journals (Sweden)

    Jared B Ditkowsky

    Full Text Available Novel tuberculosis vaccines are in varying stages of pre-clinical and clinical development. This study seeks to estimate the potential cost-effectiveness of a BCG booster vaccine, while accounting for costs of large-scale clinical trials, using the MVA85A vaccine as a case study for estimating potential costs. We conducted a decision analysis from the societal perspective, using a 10-year time frame and a 3% discount rate. We predicted active tuberculosis cases and tuberculosis-related costs for a hypothetical cohort of 960,763 South African newborns (total born in 2009. We compared neonatal vaccination with bacille Calmette-Guérin alone to vaccination with bacille Calmette-Guérin plus a booster vaccine at 4 months. We considered booster efficacy estimates ranging from 40% to 70%, relative to bacille Calmette-Guérin alone. We accounted for the costs of Phase III clinical trials. The booster vaccine was assumed to prevent progression to active tuberculosis after childhood infection, with protection decreasing linearly over 10 years. Trial costs were prorated to South Africa's global share of bacille Calmette-Guérin vaccination. Vaccination with bacille Calmette-Guérin alone resulted in estimated tuberculosis-related costs of $89.91 million 2012 USD, and 13,610 tuberculosis cases in the birth cohort, over the 10 years. Addition of the booster resulted in estimated cost savings of $7.69-$16.68 million USD, and 2,800-4,160 cases averted, for assumed efficacy values ranging from 40%-70%. A booster tuberculosis vaccine in infancy may result in net societal cost savings as well as fewer active tuberculosis cases, even if efficacy is relatively modest and large scale Phase III studies are required.

  2. Potentiation of Artemisinin Activity against Chloroquine-Resistant Plasmodium falciparum Strains by Using Heme Models

    Science.gov (United States)

    Benoit-Vical, Françoise; Robert, Anne; Meunier, Bernard

    1999-01-01

    The influence of different metalloporphyrin derivatives on the antimalarial activity of artemisinin was studied with two chloroquine-resistant strains of Plasmodium falciparum (FcB1-Colombia and FcM29-Cameroon) cultured in human erythrocytes. This potentiation study indicates that the manganese complex of meso-tetrakis(4-sulfonatophenyl)porphyrin has a significant synergistic effect on the activity of artemisinin against both Plasmodium strains. PMID:10508044

  3. Channel sialic acids limit hERG channel activity during the ventricular action potential.

    Science.gov (United States)

    Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

    2013-02-01

    Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

  4. Promoting blood vessel growth in ischemic diseases: challenges in translating preclinical potential into clinical success

    Directory of Open Access Journals (Sweden)

    Galina Dragneva

    2013-03-01

    Full Text Available Angiogenic therapy, which involves the use of an exogenous stimulus to promote blood vessel growth, is an attractive approach for the treatment of ischemic diseases. It has been shown in animal models that the stimulation of blood vessel growth leads to the growth of the whole vascular tree, improvement of ischemic tissue perfusion and improved muscle aerobic energy metabolism. However, very few positive results have been gained from Phase 2 and 3 clinical angiogenesis trials. Many reasons have been given for the failures of clinical trials, including poor transgene expression (in gene-therapy trials and instability of the vessels induced by therapy. In this Review, we discuss the selection of preclinical models as one of the main reasons why clinical translation has been unsuccessful thus far. This issue has received little attention, but could have had dramatic implications on the expectations of clinical trials. We highlight crucial differences between human patients and animal models with regards to blood flow and pressure, as well as issues concerning the chronic nature of ischemic diseases in humans. We use these as examples to demonstrate why the results from preclinical trials might have overestimated the efficacy of angiogenic therapies developed to date. We also suggest ways in which currently available animal models of ischemic disease could be improved to better mimic human disease conditions, and offer advice on how to work with existing models to avoid overestimating the efficacy of new angiogenic therapies.

  5. Clinical characteristics of papillomavirus-vulvovaginitis. A new entity with oncogenic potential.

    Science.gov (United States)

    Bodén, E; Eriksson, A; Rylander, E; von Schoultz, B

    1988-01-01

    The purpose of this paper is to describe the clinical characteristics of HPV-vulvovaginitis. Clinical symptoms were recorded in 74 women with the diagnosis of papillomavirus vulvovaginitis. The diagnosis was established by colposcopic examination, immunological detection of viral structural antigen, and selected biopsies. Patient data were obtained from medical records and by interviews. Discharge, itching, burning, fissures and dyspareunia were typical symptoms. Discharge was more frequent in women with vaginal localization of the HPV infection, whereas itching and burning were the predominant complaint when the HPV lesions were present on the vulva. However, 14 women were asymptomatic. Thirty-nine women had atypical Pap smears. In half of these women, there was no evidence of intra-epithelial neoplasia. In 15 women with atypical Pap smears there was no clinical affection of the cervix uteri. But manifestations of wart virus infection in the vagina and/or vulva. Papillomavirus vulvovaginitis may be a subclinical infection, but many women suffer from distinct symptoms related to the location of the specific lesions. This infection of the vulva and vagina may be the sole cause of atypical Pap smears. The clinical recognition of this condition is a necessary prerequisite for a rational therapeutic approach.

  6. Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials

    Directory of Open Access Journals (Sweden)

    Minnie Au

    2016-08-01

    Full Text Available Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009.

  7. Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines.

    Science.gov (United States)

    Jamal, Salma; Scaria, Vinod

    2014-01-01

    Background. Traditional Chinese medicine encompasses a well established alternate system of medicine based on a broad range of herbal formulations and is practiced extensively in the region for the treatment of a wide variety of diseases. In recent years, several reports describe in depth studies of the molecular ingredients of traditional Chinese medicines on the biological activities including anti-bacterial activities. The availability of a well-curated dataset of molecular ingredients of traditional Chinese medicines and accurate in-silico cheminformatics models for data mining for antitubercular agents and computational filters to prioritize molecules has prompted us to search for potential hits from these datasets. Results. We used a consensus approach to predict molecules with potential antitubercular activities from a large dataset of molecular ingredients of traditional Chinese medicines available in the public domain. We further prioritized 160 molecules based on five computational filters (SMARTSfilter) so as to avoid potentially undesirable molecules. We further examined the molecules for permeability across Mycobacterial cell wall and for potential activities against non-replicating and drug tolerant Mycobacteria. Additional in-depth literature surveys for the reported antitubercular activities of the molecular ingredients and their sources were considered for drawing support to prioritization. Conclusions. Our analysis suggests that datasets of molecular ingredients of traditional Chinese medicines offer a new opportunity to mine for potential biological activities. In this report, we suggest a proof-of-concept methodology to prioritize molecules for further experimental assays using a variety of computational tools. We also additionally suggest that a subset of prioritized molecules could be used for evaluation for tuberculosis due to their additional effect against non-replicating tuberculosis as well as the additional hepato-protection offered by

  8. Post-activation Potentiation in Propulsive Force after Specific Swimming Strength Training.

    Science.gov (United States)

    Barbosa, A C; Barroso, R; Andries, O

    2016-04-01

    We investigated whether a conditioning activity (8×12.5 m with 2.5 min-interval using both hand paddles and parachute) induced post-activation potentiation in swimming propulsive force and whether a swimmer's force level affected a post-activation potentiation response. 8 competitive swimmers (5 males and 3 females, age: 18.4±1.3 years; IPS=796±56) performed a 10 s maximum tethered swimming test 8 and 4 min before (the highest value was considered as PRE), and 2.5 and 6.5 min after (POST1 and POST2, respectively) the conditioning activity. Rate of force development was not affected, but peak force in POST1 (p=0.02) and impulse in both POST1 (p=0.007) and POST2 (p=0.004) were reduced. Possibly the conditioning activity induced greater fatigue than post-activation potentiation benefits. For instance, the number of repetitions might have been excessive, and rest intervals between the conditioning activity and POST1 and POST2 were possibly too short. There were positive correlations between PRE peak force and changes in peak force and rate of force development. Although conditioning activity was detrimental, positive correlations suggest that weaker swimmers experience a deterioration of performance more than the stronger ones. This conditioning activity is not recommended for swimmers with the current competitive level before a competitive event. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Antioxidant activity via DPPH, gram-positive and gram-negative antimicrobial potential in edible mushrooms.

    Science.gov (United States)

    Ahmad, Nisar; Mahmood, Fazal; Khalil, Shahid Akbar; Zamir, Roshan; Fazal, Hina; Abbasi, Bilal Haider

    2014-10-01

    Edible mushrooms (EMs) are nutritionally rich source of proteins and essential amino acids. In the present study, the antioxidant activity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial potential in EMs (Pleurotus ostreatus, Morchella esculenta, P. ostreatus (Black), P. ostreatus (Yellow) and Pleurotus sajor-caju) were investigated. The DPPH radical scavenging activity revealed that the significantly higher activity (66.47%) was observed in Morchella esculenta at a maximum concentration. Similarly, the dose-dependent concentrations (200, 400, 600, 800 and 1000 µg) were also used for other four EMs. Pleurotus ostreatus exhibited 36.13% activity, P. ostreatus (Black (B)) exhibited 30.64%, P. ostreatus (Yellow (Y)) exhibited 40.75% and Pleurotus sajor-caju exhibited 47.39% activity at higher concentrations. Furthermore, the antimicrobial potential were investigated for its toxicity against gram-negative bacterial strains (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Klebsiella pneumonia, Erwinia carotovora and Agrobacterium tumifaciens), gram-positive bacterial strains (Bacillus subtilis, Bacillus atrophaeus and Staphylococcus aureus) and a fungal strain (Candida albicans) in comparison with standard antibiotics. Antimicrobial screening revealed that the ethanol extract of P. ostreatus was active against all microorganism tested except E. coli. Maximum zone of inhibition (13 mm) was observed against fungus and A. tumifaciens. P. sajor-caju showed best activities (12.5 mm) against B. subtilis, B. atrophaeus and K. pneumonia. P. ostreatus (Y) showed best activities against P. aeroginosa (21.83 mm), B. atrophaeus (20 mm) and C. albicans (21 mm). P. ostreatus (B) exhibited best activities against C. albicans (16 mm) and slightly lower activities against all other microbes except S. typhi. M. esculenta possess maximum activities in terms of inhibition zone against all microorganisms tested except S. typhi. © The Author(s) 2012.

  10. HIV life cycle and potential targets for drug activity | Miller | Southern ...

    African Journals Online (AJOL)

    HIV life cycle and potential targets for drug activity. S Miller. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

  11. RECEPTOR POTENTIAL AND LIGHT-INDUCED MITOCHONDRIAL ACTIVATION IN BLOWFLY PHOTORECEPTOR MUTANTS

    NARCIS (Netherlands)

    MOJET, MH; TINBERGEN, J; STAVENGA, DG

    1991-01-01

    1. Simultaneous measurements of the receptor potential and the light-induced mitochondrial activation were performed in white-eyed blowflies Calliphora vicina, mutant chalky, and Lucilia cuprina, mutants w(F) and w'nss. The intensity dependence and the temporal dynamics were investigated. 2. The

  12. Single-active-electron potentials for molecules in intense laser fields

    DEFF Research Database (Denmark)

    Abu-Samha, Mahmoud; Madsen, Lars Bojer

    2010-01-01

    Single-active-electron potentials are computed for selected molecules, and molecular wave functions with the correct asymptotic behavior are produced. Asymptotic expansion coefficients are extracted from the wave functions and used to compute alignment-dependent ionization yields from molecular t...

  13. The Potential of Using Virtual Reality Technology in Physical Activity Settings

    Science.gov (United States)

    Pasco, Denis

    2013-01-01

    In recent years, virtual reality technology has been successfully used for learning purposes. The purposes of the article are to examine current research on the role of virtual reality in physical activity settings and discuss potential application of using virtual reality technology to enhance learning in physical education. The article starts…

  14. Reaching their potential: Perceived impact of a collaborative academic-clinical partnership programme for early career nurses in New Zealand.

    Science.gov (United States)

    McKillop, Ann; Doughty, Lesley; Atherfold, Cheryl; Shaw, Kathy

    2016-01-01

    The dynamic nature of healthcare ensures that early career nurses enter an uncertain and complex world of practice and consequently require support to develop their practice, build confidence and reach their potential. The New Zealand Nurse Entry to Practice programme for registered nurses in their first year of practice has been operating since 2005 to enable safe and confident practice, improve the quality of care, and positively impact on recruitment and retention. This academic and clinical programme was offered as a partnership between a university and a clinical provider with postgraduate academic credits gained. The aim of this study was to explore the perceived impact of postgraduate university education for early career nurses in one regional health area of New Zealand. Participants were registered nurses who had completed the early career nurse programme and their clinical preceptors. The research was conducted via an online survey of 248 nurses and three focus groups to explore how the programme was experienced and its impact on knowledge and practice. Early career nurses and their preceptors found that the programme enables improved knowledge and skills of patient assessment, application of critical thinking to clinical practice, perceived improvement in patient care delivery and outcomes, enhanced interprofessional communication and knowledge sharing, and had a positive impact on professional awareness and career planning. This clinical-academic partnership positively impacted on the clinical practice and transition experience of early career nurses and was closely aligned to an organization's strategic plan for nursing workforce development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Detachable glass microelectrodes for recording action potentials in active moving organs.

    Science.gov (United States)

    Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

    2017-06-01

    Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable

  16. Antioxidant activity, acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum extracts

    Directory of Open Access Journals (Sweden)

    Elena Neagu

    2018-03-01

    Full Text Available In this study several investigations and tests were performed to determine the antioxidant activity and the acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum aqueous extracts (10% mass and ethanolic extracts (10% mass and 70% ethanol, respectively. Moreover, for each type of the prepared extracts of P. officinalis and of C. umbellatum the content in the biologically active compounds – polyphenols, flavones and proanthocyanidins was determined. The antioxidant activity was assessed using two methods, namely the 2,2-diphenyl-1-picrylhydrazyl (DPPH assay and reducing power assay. The analyzed plant extracts showed a high acetylcholinesterase and tyrosinase inhibitory activity in the range of 72.24–94.24% (at the highest used dose – 3 mg/mL, 66.96% and 94.03% (at 3 mg/mL, respectively correlated with a high DPPH radical inhibition – 70.29–84.9% (at 3 mg/mL. These medicinal plants could provide a potential natural source of bioactive compounds and could be beneficial to the human health, especially in the neurodegenerative disorders and as sources of natural antioxidants in food industry. Keywords: Acetylcholinesterase inhibitory activity, Tyrosinase inhibitory activity, Antioxidant activity, Pulmonaria officinalis and Centarium umbellatum

  17. Omics-based biomarkers: current status and potential use in the clinic

    Directory of Open Access Journals (Sweden)

    Héctor Quezada

    2017-05-01

    Full Text Available In recent years, the use of high-throughput omics technologies has led to the rapid discovery of many candidate biomarkers. However, few of them have made the transition to the clinic. In this review, the promise of omics technologies to contribute to the process of biomarker development is described. An overview of the current state in this area is presented with examples of genomics, proteomics, transcriptomics, metabolomics and microbiomics biomarkers in the field of oncology, along with some proposed strategies to accelerate their validation and translation to improve the care of patients with neoplasms. The inherent complexity underlying neoplasms combined with the requirement of developing well-designed biomarker discovery processes based on omics technologies present a challenge for the effective development of biomarkers that may be useful in guiding therapies, addressing disease risks, and predicting clinical outcomes.

  18. Issues and promise in clinical studies of botanicals with anticonvulsant potential.

    Science.gov (United States)

    Ekstein, Dana

    2015-11-01

    Botanicals are increasingly used by people with epilepsy worldwide. However, despite abundant preclinical data on the anticonvulsant properties of many herbal remedies, there are very few human studies assessing safety and efficacy of these products in epilepsy. Additionally, the methodology of most of these studies only marginally meets the requirements of evidence-based medicine. Although the currently available evidence for the use of cannabinoids in epilepsy is similarly lacking, several carefully designed and well controlled industry-sponsored clinical trials of cannabis derivatives are planned to be completed in the next couple of years, providing the needed reliable data for the use of these products. The choice of the best botanical candidates with anticonvulsant properties and their assessment in well-designed clinical trials may significantly improve our ability to effectively and safely treat patients with epilepsy. This article is part of a Special Issue entitled "Botanicals for Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Administered activities of 18F-FDG PET clinics in pediatrics patients in Brazil- preliminary study

    International Nuclear Information System (INIS)

    Oliveira, Cassio Miri; Sa, Lidia V. de

    2013-01-01

    A survey was conducted among the Brazilian clinical PET, with the purpose of investigating the activities administered to pediatric oncology patients and assess whether significant differences between the protocols adopted. In addition, this survey can cooperate to the suggestion diagnostic reference levels (DRLs) in nuclear medicine. Although the methodology for delivering doses by most clinics be based on patient's weight, the results showed variations of up to 191, 6% between the activities administered in clinics, even for similar devices. The average value of the distribution of activities reported was 4.46 ± 1,6 MBq /kg. These data demonstrate the need for harmonization and optimization of 18 F-FDG/PET procedures, as well as training for professionals involved in the clinical routine

  20. NHS Trusts' clinical research activity and overall CQC performance - Is there a correlation?

    Science.gov (United States)

    Jonker, L; Fisher, S J

    2015-11-01

    Since the late 2000's, the creation of the National Institute for Health Research (NIHR) has transformed clinical research activity in the United Kingdom. This study sought to establish if there is a link between clinical research activity and overall NHS Trust performance. Retrospective cohort study. Data for NHS Trust performance were obtained from public databases, namely the Care Quality Commission (CQC) 2013 risk rating for overall performance, and 2012-13 NIHR records for clinical research activity. Applying Spearman's rank analysis, none of the Trust categories showed a correlation with CQC risk rating: small hospitals, r = -0.062 (P = 0.76; n = 27); medium, r = -0.224 (P = 0.13; n = 47); large, r = -0.008 (P = 0.96; n = 57); academic, r = -0.18 (P = 0.41; n = 24). Similar results were observed when CQC risk rating was compared with the number of different clinical research studies conducted per Trust. The degree of NIHR National Portfolio clinical research activity is not significantly related to CQC risk rating, used as an indicator of overall NHS Trust performance. Other studies have previously shown that increased research activity correlates with improved mortality rates, one component of CQC risk rating scores. Alternative tools may have to be explored to evaluate the impact of clinical research on NHS Trusts and its patients. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  1. Clinical Trials in a Dish: The Potential of Pluripotent Stem Cells to Develop Therapies for Neurodegenerative Diseases.

    Science.gov (United States)

    Haston, Kelly M; Finkbeiner, Steven

    2016-01-01

    Neurodegenerative diseases are a leading cause of death. No disease-modifying therapies are available, and preclinical animal model data have routinely failed to translate into success for therapeutics. Induced pluripotent stem cell (iPSC) biology holds great promise for human in vitro disease modeling because these cells can give rise to any cell in the human brain and display phenotypes specific to neurodegenerative diseases previously identified in postmortem and clinical samples. Here, we explore the potential and caveats of iPSC technology as a platform for drug development and screening, and the future potential to use large cohorts of disease-bearing iPSCs to perform clinical trials in a dish.

  2. Clinical Trials in a Dish: The Potential of Pluripotent Stem Cells to Develop Therapies for Neurodegenerative Diseases

    Science.gov (United States)

    Haston, Kelly M.; Finkbeiner, Steven

    2016-01-01

    Neurodegenerative diseases are a leading cause of death. No disease-modifying therapies are available, and preclinical animal model data have routinely failed to translate into success for therapeutics. Induced pluripotent stem cell (iPSC) biology holds great promise for human in vitro disease modeling because these cells can give rise to any cell in the human brain and display phenotypes specific to neurodegenerative diseases previously identified in postmortem and clinical samples. Here, we explore the potential and caveats of iPSC technology as a platform for drug development and screening, and the future potential to use large cohorts of disease-bearing iPSCs to perform clinical trials in a dish. PMID:26514199

  3. Differences in Genotype, Clinical Features, and Inflammatory Potential of Borrelia burgdorferi sensu stricto Strains from Europe and the United States

    Science.gov (United States)

    Cerar, Tjasa; Strle, Franc; Stupica, Dasa; Ruzic-Sabljic, Eva; McHugh, Gail; Steere, Allen C.

    2016-01-01

    Borrelia burgdorferi sensu stricto isolates from patients with erythema migrans in Europe and the United States were compared by genotype, clinical features of infection, and inflammatory potential. Analysis of outer surface protein C and multilocus sequence typing showed that strains from these 2 regions represent distinct genotypes. Clinical features of infection with B. burgdorferi in Slovenia were similar to infection with B. afzelii or B. garinii, the other 2 Borrelia spp. that cause disease in Europe, whereas B. burgdorferi strains from the United States were associated with more severe disease. Moreover, B. burgdorferi strains from the United States induced peripheral blood mononuclear cells to secrete higher levels of cytokines and chemokines associated with innate and Th1-adaptive immune responses, whereas strains from Europe induced greater Th17-associated responses. Thus, strains of the same B. burgdorferi species from Europe and the United States represent distinct clonal lineages that vary in virulence and inflammatory potential. PMID:27088349

  4. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  5. Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies.

    Science.gov (United States)

    Thu, Hnin Ei; Mohamed, Isa Naina; Hussain, Zahid; Jayusman, Putri Ayu; Shuid, Ahmad Nazrun

    2017-01-01

    Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  6. Theileriosis in six dogs in South Africa and its potential clinical significance

    Directory of Open Access Journals (Sweden)

    Chantal T. Rosa

    2014-08-01

    Full Text Available Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4and Theileria equi (n = 2 were detected by a polymerase chain reaction (PCR-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs, bleeding tendencies (five out of six dogs and lethargy (three out of six dogs. All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.

  7. Biochemical and Functional Characterization of Parawixia bistriata Spider Venom with Potential Proteolytic and Larvicidal Activities

    Directory of Open Access Journals (Sweden)

    Gizeli S. Gimenez

    2014-01-01

    Full Text Available Toxins purified from the venom of spiders have high potential to be studied pharmacologically and biochemically. These biomolecules may have biotechnological and therapeutic applications. This study aimed to evaluate the protein content of Parawixia bistriata venom and functionally characterize its proteins that have potential for biotechnological applications. The crude venom showed no phospholipase, hemorrhagic, or anti-Leishmania activities attesting to low genotoxicity and discrete antifungal activity for C. albicans. However the following activities were observed: anticoagulation, edema, myotoxicity and proteolysis on casein, azo-collagen, and fibrinogen. The chromatographic and electrophoretic profiles of the proteins revealed a predominance of acidic, neutral, and polar proteins, highlighting the presence of proteins with high molecular masses. Five fractions were collected using cation exchange chromatography, with the P4 fraction standing out as that of the highest purity. All fractions showed proteolytic activity. The crude venom and fractions P1, P2, and P3 showed larvicidal effects on A. aegypti. Fraction P4 showed the presence of a possible metalloprotease (60 kDa that has high proteolytic activity on azo-collagen and was inhibited by EDTA. The results presented in this study demonstrate the presence of proteins in the venom of P. bistriata with potential for biotechnological applications.

  8. Biochemical and Functional Characterization of Parawixia bistriata Spider Venom with Potential Proteolytic and Larvicidal Activities

    Science.gov (United States)

    Gimenez, Gizeli S.; Coutinho-Neto, Antonio; Kayano, Anderson M.; Simões-Silva, Rodrigo; Trindade, Frances; de Almeida e Silva, Alexandre; Marcussi, Silvana; da Silva, Saulo L.; Fernandes, Carla F. C.; Zuliani, Juliana P.; Calderon, Leonardo A.; Soares, Andreimar M.; Stábeli, Rodrigo G.

    2014-01-01

    Toxins purified from the venom of spiders have high potential to be studied pharmacologically and biochemically. These biomolecules may have biotechnological and therapeutic applications. This study aimed to evaluate the protein content of Parawixia bistriata venom and functionally characterize its proteins that have potential for biotechnological applications. The crude venom showed no phospholipase, hemorrhagic, or anti-Leishmania activities attesting to low genotoxicity and discrete antifungal activity for C. albicans. However the following activities were observed: anticoagulation, edema, myotoxicity and proteolysis on casein, azo-collagen, and fibrinogen. The chromatographic and electrophoretic profiles of the proteins revealed a predominance of acidic, neutral, and polar proteins, highlighting the presence of proteins with high molecular masses. Five fractions were collected using cation exchange chromatography, with the P4 fraction standing out as that of the highest purity. All fractions showed proteolytic activity. The crude venom and fractions P1, P2, and P3 showed larvicidal effects on A. aegypti. Fraction P4 showed the presence of a possible metalloprotease (60 kDa) that has high proteolytic activity on azo-collagen and was inhibited by EDTA. The results presented in this study demonstrate the presence of proteins in the venom of P. bistriata with potential for biotechnological applications. PMID:24895632

  9. The potential of predictive analytics to provide clinical decision support in depression treatment planning.

    Science.gov (United States)

    Kessler, Ronald C

    2018-01-01

    To review progress developing clinical decision support tools for personalized treatment of major depressive disorder (MDD). Over the years, a variety of individual indicators ranging from biomarkers to clinical observations and self-report scales have been used to predict various aspects of differential MDD treatment response. Most of this work focused on predicting remission either with antidepressant medications versus psychotherapy, some antidepressant medications versus others, some psychotherapies versus others, and combination therapies versus monotherapies. However, to date, none of the individual predictors in these studies has been strong enough to guide optimal treatment selection for most patients. Interest consequently turned to decision support tools made up of multiple predictors, but the development of such tools has been hampered by small study sample sizes. Design recommendations are made here for future studies to address this problem. Recommendations include using large prospective observational studies followed by pragmatic trials rather than smaller, expensive controlled treatment trials for preliminary development of decision support tools; basing these tools on comprehensive batteries of inexpensive self-report and clinical predictors (e.g., self-administered performance-based neurocognitive tests) versus expensive biomarkers; and reserving biomarker assessments for targeted studies of patients not well classified by inexpensive predictor batteries.

  10. Potential chemopreventive activity of a new macrolide antibiotic from a marine-derived Micromonospora sp.

    Science.gov (United States)

    Carlson, Skylar; Marler, Laura; Nam, Sang-Jip; Santarsiero, Bernard D; Pezzuto, John M; Murphy, Brian T

    2013-04-03

    Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1), as well as 5-O-α-L-rhamnosyltylactone (2), were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses.

  11. Perceived outcomes of research and audit activities of clinical specialists in Ireland.

    Science.gov (United States)

    Begley, Cecily; Elliott, Naomi; Lalor, Joan G; Higgins, Agnes

    2015-01-01

    The objectives of this study were to ascertain whether clinical specialists in Ireland were fulfilling role expectations in terms of their involvement in audit, evidence-based practice, and research activities; to examine the perceived impact on practice of clinical specialists'/advanced practitioners' research and audit roles and activities; and to compare research and audit activity in sites with and without clinical specialists/advanced practitioners. This was a sequential, mixed-methods case study. The study was performed in clinical specialists'/advanced practitioners' hospital and community practice settings, and matched sites with no specialist/advanced practitioner, in each healthcare region in Ireland. A purposive sample of 17 clinical nurse or midwife specialists and 6 advanced nurse practitioners was selected, and 23 "matched" sites in hospital/services that provided similar client care were chosen. Midwifery and all branches of nursing were included. Data were collected January 2008 to December 2010, using nonparticipant observation (184 hours) of specialist/advanced practitioners and matched clinicians in practice, interviews with directors of nursing/midwifery (n = 23) and clinicians (n = 41), and analysis of documents from each case-study site. Pairs of researchers checked each other's work, negative case analysis was used, and the whole team agreed with the final findings. Clinical specialists/advanced practitioners demonstrated more evidence-based practice and greater use of audit than did other clinicians fulfilling comparable clinical roles in matched sites. Fifteen specialist/advanced practitioners (65%) compared with 7 clinicians in matched sites (30%) conducted research (P audit, evidence-based practice, and research. The impact of clinical specialists' activities in this area, as perceived by clinical colleagues and managers, is considerable and is documented as greater than the impact of nonspecialist colleagues in comparable sites

  12. THEORETICAL AND PRACTICAL ASPECTS OF EXPLORATION THE INNOVATIVE ACTIVE ORGANIZATIONS’ POTENTIAL OF A BALANCED DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    A. I. Khorev

    2014-01-01

    Full Text Available Summary. The concept of "potential" put into practice as a method of study permits the uncertainty associated with the absence of any information about the conditions of functioning in the future. Critical importance is the study of the potential development of an economic entity. S.I. Ozhegov noted that development - natural process changes, the transition from one state to another, more perfect, the transition from an old qualitative state to a new, simple to complex, from lowest to highest. The essential content of balanced development potential based on study of the relationship concepts of «potential of the company», «the development of an economic entity», «balanced development» have been considered in the article. Particular attention is paid to the specifics of development of innovation-active organizations. Conclusion has been made that to the timely detection of potential balanced development need a comprehensive analysis of the conditions and factors functioning economic entity, which have been grouped into three groups: factors of macro, meso and micro level. A comprehensive study of the factors determining the future development of innovation-active enterprises has been conducted in the article. It is shown that the effectiveness of the balanced development of innovation-active organizations in general, and the object of research , in particular , is determined by such factors as the structure and needs of the market , the resource base of innovative development , effective management system development, innovation activity . The authors believe that the inclusion of the multifaceted impact of factors will allow innovative active organizations to build a control system which allows more accurately predict the perspective direction of their future development.

  13. Virtual screening and statistical analysis in the design of new caffeine analogues molecules with potential epithelial anticancer activity.

    Science.gov (United States)

    Costa, Josivan da Silva; Costa, Karina Da Silva Lopes; Cruz, Josiane Viana; Ramosb, Ryan da Silva; Silva, Luciane Barros; Barros Brasilc, Davi Do Socorro; Henrique Tomich de Paula da Silva, Carlos; Santos, Cleydson Breno Rodrigues Dos; Macêdoe, Williams Jorge da Cruz

    2017-07-11

    About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the world health organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Discriminating active from latent tuberculosis in patients presenting to community clinics.

    Directory of Open Access Journals (Sweden)

    Gurjinder Sandhu

    Full Text Available Because of the high global prevalence of latent TB infection (LTBI, a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics.Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI.156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%, from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82% and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%.We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.

  15. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Vind, Ida; Johansen, J S; Price, P A

    2003-01-01

    BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek ass...... were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity....

  16. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Vind, Ida; Johansen, J S; Price, P A

    2003-01-01

    BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek...... were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity....

  17. Active action potential propagation but not initiation in thalamic interneuron dendrites

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  18. Influence of clinical use on physical-structural surface properties and electrochemical potential of NiTi endodontic instruments.

    Science.gov (United States)

    Pereira, E S J; Amaral, C C F; Gomes, J A C P; Peters, O A; Buono, V T L; Bahia, M G A

    2017-03-22

    To investigate the surface morphology and electrochemical potential of superelastic (SE), M-Wire (MW) and shape memory technology (SMT) NiTi instruments before and after single clinical use in vivo. A total of 60 ProTaper Universal F2 (PTU-SE), ProTaper Next X2 (PTN-MW), Typhoon (TYP), Hyflex (HF) and Vortex Blue (VB), the last three SMT, and size 25, .06 taper (n = 6 of each type) files were examined. Scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS) and electrochemical potential analysis were employed before and after clinical use. Statistical analysis was performed with one-way analysis of variance and Bonferroni's post hoc test. Significance was determined at the 95% confidence level for both tests. SEM observations of new instruments indicated the presence of marks left by the machining process during manufacturing and EDS revealed the existence of an oxide coating on shape memory instruments. After clinical use, the five types were associated with propagation of transverse cracks 3 mm from the tip. The surface oxide layer of TYP, HF and VB instruments had microcracks in multiple directions, whilst TYP and HF had fragmentation in chip form of the oxide layer. EDS analysis demonstrated a significant reduction of the oxide layer in shape memory instruments, except for VB. Electrochemical potentials were higher for shape memory instruments than for M-Wire and superelastic NiTi instruments, respectively (P NiTi instruments have a dysfunctional oxide layer after clinical use. Additionally, they featured higher electrochemical potential relative to NiTi instruments manufactured from M-Wire, and conventional superelastic NiTi alloy. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  19. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Hantson, Philippe [Universite Catholique de Louvain, Department of Intensive Care, Cliniques Saint-Luc, Brussels (Belgium); Grandin, Cecile; Duprez, Thierry [Universite Catholique de Louvain, Department of Neuroradiology, Cliniques Saint-Luc, Brussels (Belgium); Nassogne, Marie-Cecile [Universite Catholique de Louvain, Department of Pediatric Neurology, Cliniques Saint-Luc, Brussels (Belgium); Guerit, Jean-Michel [Universite Catholique de Louvain, Laboratory of Neurophysiology, Cliniques Saint-Luc, Brussels (Belgium)

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 {mu}mol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  20. Prevalence and clinical outcomes of patients with multiple potential causes of syncope

    NARCIS (Netherlands)

    Chen, Lin Y.; Gersh, Bernard J.; Hodge, David O.; Wieling, Wouter; Hammill, Stephen C.; Shen, Win-Kuang

    2003-01-01

    Objective: To determine the prevalence, predictors, and prognosis of patients with multiple potential causes of syncope. Patients and Methods: This is a retrospective cohort study with prospective follow-up of consecutive patients with syncope of uncertain cause who were referred to the

  1. Iranian Clinical Nurses' Activities for Self-Directed Learning: A Qualitative Study.

    Science.gov (United States)

    Ghiyasvandian, Shahrzad; Malekian, Morteza; Cheraghi, Mohammad Ali

    2015-09-01

    Clinical nurses need lifelong learning skills for responding to the rapid changes of clinical settings. One of the best strategies for lifelong learning is self-directed learning. The aim of this study was to explore Iranian clinical nurses' activities for self-directed learning. In this qualitative study, 23 semi-structured personal interviews were conducted with nineteen clinical nurses working in all four hospitals affiliated to Isfahan Social Security Organization, Isfahan, Iran. Study data were analyzed by using the content analysis approach. The study was conducted from June 2013 to October 2014. Study participants' activities for self-directed learning fell into two main categories of striving for knowledge acquisition and striving for skill development. The main theme of the study was 'Revising personal performance based on intellectual-experiential activities'. Study findings suggest that Iranian clinical nurses continually revise their personal performance by performing self-directed intellectual and experiential activities to acquire expertise. The process of acquiring expertise is a linear process which includes two key steps of knowledge acquisition and knowledge development. In order to acquire and advance their knowledge, nurses perform mental learning activities such as sensory perception, self-evaluation, and suspended judgment step-by-step. Moreover, they develop their skills through doing activities like apprenticeship, masterly performance, and self-regulation. The absolute prerequisite to expertise acquisition is that a nurse needs to follow these two steps in a sequential manner.

  2. Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial Repair: Clinical Translatability and Potential Limitation.

    Science.gov (United States)

    Wu, Rongrong; Hu, Xinyang; Wang, Jian'an

    2018-01-13

    Ischemic heart diseases (IHDs) remain major public health problems with high rates of morbidity and mortality worldwide. Despite significant advances, current therapeutic approaches are unable to rescue the extensive and irreversible loss of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell-based therapy has been recognized as an innovative strategy for cardiac repair/regeneration and functional recovery after IHDs. Although substantial preclinical animal studies using a variety of stem/progenitor cells have shown promising results, there is a tremendous degree of skepticism in the clinical community as many stem cell trials do not confer any beneficial effects. How to accelerate stem cell-based therapy toward successful clinical application attracts considerate attention. However, many important issues need to be fully addressed. In this Review, we have described and compared the effects of different types of stem cells with their dose, delivery routes, and timing that have been routinely tested in recent preclinical and clinical findings. We have also discussed the potential mechanisms of action of stem cells, and explored the role and underlying regulatory components of stem cell-derived secretomes/exosomes in myocardial repair. Furthermore, we have critically reviewed the different strategies for optimizing both donor stem cells and the target cardiac microenvironments to enhance the engraftment and efficacy of stem cells, highlighting their clinical translatability and potential limitation. Stem Cells 2018. © AlphaMed Press 2018.

  3. Hemolytic activity of Trichomonas gallinae isolates does not correspond with clinical virulence.

    Science.gov (United States)

    Gerhold, Richard W; Yabsley, Michael J; Fischer, John R

    2009-03-23

    The hemolytic activity of 22 Trichomonas gallinae isolates was investigated using an 18h erythrocyte hemolysis assay which has been shown to correlate with the clinical virulence of T. vaginalis. Absorbance of the assay supernatants was measured at 540nm and expressed as percentage of complete hemolysis. Mean hemolytic activity of the T. gallinae isolates ranged from 3.5% to 53.4% and did not correspond with clinical virulence. The results of this investigation suggest hemolytic activity is not a useful in vitro virulence assay for T. gallinae.

  4. Preliminary clinical results: an analyzing tool for 2D optical imaging in detection of active inflammation in rheumatoid arthritis

    Science.gov (United States)

    Adi Aizudin Bin Radin Nasirudin, Radin; Meier, Reinhard; Ahari, Carmen; Sievert, Matti; Fiebich, Martin; Rummeny, Ernst J.; No"l, Peter B.

    2011-03-01

    Optical imaging (OI) is a relatively new method in detecting active inflammation of hand joints of patients suffering from rheumatoid arthritis (RA). With the high number of people affected by this disease especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this paper, we present a newly in-house developed OI analyzing tool and a clinical evaluation study. Our analyzing tool extends the capability of existing OI tools. We include many features in the tool, such as region-based image analysis, hyper perfusion curve analysis, and multi-modality image fusion to aid clinicians in localizing and determining the intensity of inflammation in joints. Additionally, image data management options, such as the full integration of PACS/RIS, are included. In our clinical study we demonstrate how OI facilitates the detection of active inflammation in rheumatoid arthritis. The preliminary clinical results indicate a sensitivity of 43.5%, a specificity of 80.3%, an accuracy of 65.7%, a positive predictive value of 76.6%, and a negative predictive value of 64.9% in relation to clinical results from MRI. The accuracy of inflammation detection serves as evidence to the potential of OI as a useful imaging modality for early detection of active inflammation in patients with rheumatoid arthritis. With our in-house developed tool we extend the usefulness of OI imaging in the clinical arena. Overall, we show that OI is a fast, inexpensive, non-invasive and nonionizing yet highly sensitive and accurate imaging modality.-

  5. In vitro Serotonergic Activity of Black Cohosh and Identification of Nω-Methylserotonin as a Potential Active Constituent

    Science.gov (United States)

    POWELL, SHARLA L.; GÖDECKE, TANJA; NIKOLIC, DEJAN; CHEN, SHAO-NONG; AHN, SOYOUN; DIETZ, BIRGIT; FARNSWORTH, NORMAN R.; VAN BREEMEN, RICHARD B.; LANKIN, DAVID; PAULI, GUIDO F.; BOLTON, JUDY L.

    2013-01-01

    Cimicifuga racemosa(L.) Nutt. (syn. Actaea racemosa L., black cohosh) is used to relieve menopausal hot flashes, although clinical studies have provided conflicting data, and the active constituent(s) and mechanism(s) of action remain unknown. Since serotonergic receptors and transporters are involved with thermoregulation, black cohosh and its phytoconstituents were evaluated for serotonergic activity using 5-HT7 receptor binding, cAMP induction, and serotonin selective reuptake inhibitor (SSRI) assays. Crude extracts displayed 5-HT7 receptor binding activity and induced cAMP production. Fractionation of the methanol extract lead to isolation of phenolic acids and identification of Nω-methylserotonin by LC/MS-MS. Cimicifuga triterpenoids and phenolic acids bound weakly to the 5-HT7 receptor with no cAMP or SSRI activity. In contrast, Nω-methylserotonin showed 5-HT7 receptor binding (IC50 23 pM), induced cAMP (EC50 22 nM), and blocked serotonin reuptake (IC50 490 nM). These data suggest Nω-methylserotonin may be responsible for the serotonergic activity of black cohosh. PMID:19049296

  6. Utilizing Focus Groups with Potential Participants and Their Parents: An Approach to Inform Study Design in a Large Clinical Trial.

    Science.gov (United States)

    Kadimpati, Sandeep; McCormick, Jennifer B; Chiu, Yichen; Parker, Ashley B; Iftikhar, Aliya Z; Flick, Randall P; Warner, David O

    2014-01-01

    In the recent literature, there has been some evidence that exposure of children to anesthetic procedures during the first two years of life may impair cognitive function and learning in later life. We planned a clinical study to quantify this risk, a study involving testing 1,000 children for neurodevelopmental deficits. As a part of this planning, we conducted focus groups involving potential participants and their parents to elicit information regarding three issues: communications with the community and potential participants, recruitment and consent processes, and the return of neurodevelopmental testing results. Three focus groups were conducted with the parents of potential participants and one focus group was conducted with an 18-19 year old group; each group consisted of 6-10 participants. The moderated discussions had questions about recruitment, consenting issues, and expectations from the study about return of both overall trial findings and individual research test results. The focus group data gave us an insight on potential participants' views on recruitment, consenting, communications about the study, and expectations about return of both overall trial findings and individual research test results. The concerns expressed were largely addressable. In addition, the concern we had about some parents enrolling their children in the study solely for the sake of getting their child's cognitive function results was dispelled. We found that the individuals participating in our focus groups were generally enthusiastic about the large clinical study and could see the value in answering the study question. The data from the focus groups were used to inform changes to the recruitment and consent process. Focus group input was also instrumental in affirming the study design regarding return of results. Our experience suggests that the approach we used may serve as a model for other investigators to help inform the various elements of clinical study design, in

  7. High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications

    International Nuclear Information System (INIS)

    Aide, Nicolas; Desmonts, Cedric; Agostini, Denis; Bardet, Stephane; Bouvard, Gerard; Beauregard, Jean-Mathieu; Roselt, Peter; Neels, Oliver; Beyer, Thomas; Kinross, Kathryn; Hicks, Rodney J.

    2010-01-01

    The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three