WorldWideScience

Sample records for valuable therapeutic approach

  1. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  2. PYTHIOSIS: A THERAPEUTIC APPROACH

    Directory of Open Access Journals (Sweden)

    C. M. C. Falcão

    2015-10-01

    Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

  3. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    Although prevention is the ideal goal for genetic disorders, various types of therapeutic ... The patient being ... pirical or aimed at controlling or mediating signs and symptoms without care. ... plications and gene therapy approaches .... genes family, have opened a wide and .... cancer where nanoparticles are used to.

  4. Ab Interno Trabeculectomy With the Trabectome as a Valuable Therapeutic Option for Failed Filtering Blebs.

    Science.gov (United States)

    Wecker, Thomas; Neuburger, Matthias; Bryniok, Laura; Bruder, Kathrin; Luebke, Jan; Anton, Alexandra; Jordan, Jens F

    2016-09-01

    . The number of necessary IOP lowering medication drops at first, but seems to reach preoperative values after 20 months of follow-up. Trabectome surgery should be considered as a valuable escape procedure for patients with failed filtering blebs and uncontrolled IOP.

  5. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  6. Novel therapeutic approaches in chondrosarcoma.

    Science.gov (United States)

    Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

    2017-03-01

    Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

  7. Toxin-Based Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Itai Benhar

    2010-10-01

    Full Text Available Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.

  8. Toxin-Based Therapeutic Approaches

    Science.gov (United States)

    Shapira, Assaf; Benhar, Itai

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

  9. Malignant mesothelioma: biology, diagnosis and therapeutic approaches

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Amati, M.; Santarelli, L.; Alleva, R.; Neužil, Jiří

    2009-01-01

    Roč. 2, č. 2 (2009), s. 190-206 ISSN 1874-4672 Institutional research plan: CEZ:AV0Z50520514 Keywords : malignant mesothelioma * biology * diagnosis and therapeutic approaches Subject RIV: EB - Genetics ; Molecular Biology

  10. Three Valuable Peptides from Bee and Wasp Venoms for Therapeutic and Biotechnological Use: Melittin, Apamin and Mastoparan

    Science.gov (United States)

    Moreno, Miguel; Giralt, Ernest

    2015-01-01

    While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of these venoms are now being studied with the aim to design and develop new therapeutic drugs. Far from evaluating the extensive number of monographs, journals and books related to bee and wasp venoms and the therapeutic effect of these toxins in numerous diseases, the following review focuses on the three most characterized peptides, namely melittin, apamin, and mastoparan. Here, we update information related to these compounds from the perspective of applied science and discuss their potential therapeutic and biotechnological applications in biomedicine. PMID:25835385

  11. Interpreting quantum theory a therapeutic approach

    CERN Document Server

    Friederich, S

    2014-01-01

    Is it possible to approach quantum theory in a 'therapeutic' vein that sees its foundational problems as arising from mistaken conceptual presuppositions? The book explores the prospects for this project and, in doing so, discusses such fascinating issues as the nature of quantum states, explanation in quantum theory, and 'quantum non-locality'.

  12. An alternative approach to recovering valuable metals from zinc phosphating sludge.

    Science.gov (United States)

    Kuo, Yi-Ming

    2012-01-30

    This study used a vitrification process (with good potential for commercialization) to recover valuable metals from Zn phosphating sludge. The involved vitrification process achieves two major goals: it transformed hazardous Zn phosphating sludge into inert slag and it concentrated Fe (83.5%) and Zn (92.8%) into ingot and fine particulate-phase material, respectively. The Fe content in the ingot was 278,000 mg/kg, making the ingot a potential raw material for iron making. The fine particulate-phase material (collected from flue gas) contained abundant Zn (544,000 mg/kg) in the form of ZnO. The content (67.7%) of ZnO was high, so it can be directly sold to refineries. The recovered coarse particulate-phase material, with insufficient amount of ZnO, can be recycled as a feeding material for Zn re-concentration. Therefore, the vitrification process can not only treat hazardous materials but also effectively recover valuable metals. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Therapeutic approaches to preventing cell death in Huntington disease.

    Science.gov (United States)

    Kaplan, Anna; Stockwell, Brent R

    2012-12-01

    Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

    Science.gov (United States)

    Alsharif, Naser Z.; And Others

    1997-01-01

    Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

  15. Discrete mathematical data analysis approach: a valuable assessment method for sustainable chemistry.

    Science.gov (United States)

    Voigt, Kristina; Scherb, Hagen; Bruggemann, Rainer; Schramm, Karl-Werner

    2013-06-01

    Sustainable/Green Chemistry is a chemical philosophy encouraging the design of products and processes that reduce or eliminate the use and generation of hazardous substances. In this respect, metrical scientific disciplines like Chemometrics are important, because they indicate criteria for chemicals being hazardous or not. We demonstrated that sustainable principles in the disciplines Green Chemistry, Green Engineering, and Sustainability in Information Technology have main aspects in common. The use of non-hazardous chemicals or the more efficient use of chemical substances is one of these aspects. We take a closer look on the topic of the hazards of chemical substances. Our research focuses on data analyses concerning environmental chemicals named Persistent Organic Pollutants (POPs), which are found all over the world and pose a large risk to environment as well as to humans. The evaluation of the data is a major step in the elucidation of the danger of these chemicals. The data analysis method demonstrated here, is based on the theory of partially ordered sets and provides a generalized ranking. In our approach we investigate data sets of breast milk samples of women in Denmark, Finland, and Turkey which contained measurable levels of 20 POPs. The goal is twofold: On the one side the hazardous chemicals are to be identified and on the other side possible differences among the three nations should be detected, because in that case possible different uptake mechanisms may be supposed. The data analysis is performed by the free available software package PyHasse, written by the third author. We conclude that the data analysis method can well be applied for distinguishing between more or less dangerous existing chemicals. Furthermore, it should be used in sustainable chemistry in the same manner for detecting more and less sustainable chemicals. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Therapeutic approaches for spinal cord injury

    Directory of Open Access Journals (Sweden)

    Alexandre Fogaça Cristante

    2012-10-01

    Full Text Available This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a ''disease that should not be treated.'' Over the last biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life.

  17. Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

    Science.gov (United States)

    Kurtoğlu, Selim; Özdemir, Ahmet

    2017-01-01

    Fetal and neonatal hyperthyroidism may occur in mothers with Graves’ disease. Fetal thyrotoxicosis manifestation is observed with the transition of TSH receptor stimulating antibodies to the fetus from the 17th–20th weeks of pregnancy and with the fetal TSH receptors becoming responsive after 20 weeks. The diagnosis is confirmed by fetal tachycardia, goiter and bone age advancement in pregnancy and maternal treatment is conducted in accordance. The probability of neonatal hyperthyroidism is high in the babies of mothers that have ongoing antithyroid requirement and higher antibody levels in the last months of pregnancy. Clinical manifestation may be delayed by 7–17 days because of the antithyroid drugs taken by the mother. Neonatal hyperthyroidism symptoms can be confused with sepsis and congenital viral infections. Herein, the diagnosis and therapeutic approach are reviewed in cases of fetal neonatal hyperthyroidism. PMID:28439194

  18. Approaches to Preventative and Therapeutic HIV vaccines

    Science.gov (United States)

    Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

    2016-01-01

    Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

  19. Valuable Connections

    DEFF Research Database (Denmark)

    Kjærsgaard, Mette Gislev; Smith, Rachel Charlotte

    2014-01-01

    and blurred boundaries between physical, digital and hybrid contexts, as well as design, production and use, we might need to rethink the role of ethnography within design and business development. Perhaps the aim is less about ”getting closer” to user needs and real-life contexts, through familiarization......, mediation, advocacy and facilitation, as in conventional approaches to ethnography in user centred design, and more about creating a critical theoretically informed distance from which to perceive and reflect upon complex interconnections between people, technology, business and design, as well as our roles...

  20. Internet addiction neuroscientific approaches and therapeutical interventions

    CERN Document Server

    Reuter, Martin

    2015-01-01

    This book combines a scholarly introduction with state-of-the-art research in the characterization of Internet addiction. It is intended for a broad audience including scientists, students and practitioners. The first part of the book contains an introduction to Internet addiction and their pathogenesis. The second part of the book is dedicated to an in-depth review of neuroscientific findings which cover studies using a variety of biological techniques including brain imaging and molecular genetics. The last part of the book will focus on therapeutic interventions for Internet addiction.

  1. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    Pacheco, Ivan; Buzea, Cristina; Tron, Victor

    2011-11-01

    Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

  2. Therapeutic Approaches of Botulinum Toxin in Gynecology.

    Science.gov (United States)

    Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

    2018-04-21

    Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

  3. Therapeutic Approaches of Botulinum Toxin in Gynecology

    Directory of Open Access Journals (Sweden)

    Marius Alexandru Moga

    2018-04-01

    Full Text Available Botulinum toxins (BoNTs are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G. Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

  4. Nelson Syndrome: Update on Therapeutic Approaches.

    Science.gov (United States)

    Azad, Tej D; Veeravagu, Anand; Kumar, Sunny; Katznelson, Laurence

    2015-06-01

    To review the pathophysiology and therapeutic modalities availble for Nelson syndrome. We reviewed the current literature including managment for Nelson syndrome. For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS. An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Nanotechnology based approaches in cancer therapeutics

    International Nuclear Information System (INIS)

    Biswas, Amit Kumer; Islam, Md Reazul; Choudhury, Zahid Sadek; Kadir, Mohammad Fahim; Mostafa, Asif

    2014-01-01

    The current decades are marked not by the development of new molecules for the cure of various diseases but rather the development of new delivery methods for optimum treatment outcome. Nanomedicine is perhaps playing the biggest role in this concern. Nanomedicine offers numerous advantages over conventional drug delivery approaches and is particularly the hot topic in anticancer research. Nanoparticles (NPs) have many unique criteria that enable them to be incorporated in anticancer therapy. This topical review aims to look at the properties and various forms of NPs and their use in anticancer treatment, recent development of the process of identifying new delivery approaches as well as progress in clinical trials with these newer approaches. Although the outcome of cancer therapy can be increased using nanomedicine there are still many disadvantages of using this approach. We aim to discuss all these issues in this review. (review)

  6. Recent novel tumor gatekeepers and potential therapeutic approaches

    African Journals Online (AJOL)

    Keywords: Cancer, Potent inhibitors, Gatekeepers, Therapeutic approaches, Oncogenic pathways. Tropical Journal ..... effects of the target suppression support change from a one gene .... Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017.

  7. Clinical Significance: a Therapeutic Approach Topsychological Assessment in Treatment Planning

    Directory of Open Access Journals (Sweden)

    Afolabi Olusegun Emmanuel

    2015-06-01

    Full Text Available Psychological assessment has long been reported as a key component of clinical psychology. This paper examines the complexities surrounding the clinical significance of therapeutic approach to treatment planning. To achieve this objective, the paper searched and used the PsycINFO and PubMed databases and the reference sections of chapters and journal articles to analysed, 1 a strong basis for the usage of therapeutic approach to psychological assessment in treatment plans, 2 explained the conceptual meaning of clinical significant change in therapeutic assessment, 3 answered some of the questions regarding practicability and the clinical significance of therapeutic approach to treatment plans, particularly during or before treatment, 4 linked therapeutic assessment to change in clients’ clinical impression, functioning and therapeutic needs 5 analysed the empirically documenting clinically significant change in therapeutic assessment. Finally, the study suggested that though therapeutic assessment is not sufficient for the systematic study of psychotherapy outcome and process, it is still consistent with both the layman and professional expectations regarding treatment outcome and also provides a precise method for classifying clients as ‘changed’ or ‘unchanged’ on the basis of clinical significance criteria.

  8. Neuroimaging revolutionizes therapeutic approaches to chronic pain

    Directory of Open Access Journals (Sweden)

    Borsook David

    2007-09-01

    Full Text Available Abstract An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1 Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2 Functional Imaging (fMRI that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI; (3 Chemical Imaging (Magnetic Resonance Spectroscopy or MRS has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS.

  9. Diagnostic and therapeutic approach to hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, Alessandro D; Ricchieri, Federica; Lanzoni, Chiara; Strucchi, Claudia; Jasonni, Valerio M

    2006-12-01

    Hypothalamic amenorrhea (HA) is a secondary amenorrhea with no evidence of endocrine/systemic causal factors, mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stress conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be exclude any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stress situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This article tries to give insights into diagnosis and putative therapeutic strategies.

  10. Hypothalamic amenorrhea: from diagnosis to therapeutical approach.

    Science.gov (United States)

    Genazzani, A D; Chierchia, E; Santagni, S; Rattighieri, E; Farinetti, A; Lanzoni, C

    2010-05-01

    Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  11. Emerging Therapeutic Approaches to Mitochondrial Diseases

    Science.gov (United States)

    Wenz, Tina; Williams, Sion L.; Bacman, Sandra R.; Moraes, Carlos T.

    2010-01-01

    Mitochondrial diseases are very heterogeneous and can affect different tissues and organs. Moreover, they can be caused by genetic defects in either nuclear or mitochondrial DNA as well as by environmental factors. All of these factors have made the development of therapies difficult. In this review article, we will discuss emerging approaches to…

  12. Therapeutic Approaches to Target Cancer Stem Cells

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC

  13. [Therapeutic approach to patients with neurocardiogenic syncope].

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek; Halawa, Bogumił

    2004-11-01

    Vasovagal syncopes are the most common cause of loss of consciousness and if they occur frequently they contribute to the marked decrease of the quality of life and need treatment. One of important problems is the possibility of injury during the syncope. In older patients it can lead to the fractures of extremities, complications of which could be life-threatening. Another problem is the reaction of the surrounding people trying to help the unconscious by keeping him in the vertical position. It promotes hypotonia and could cause damage of organs such as brain or heart. The authors review the current literature on the management of patients with vasovagal syncope. It seems that the conservative approaches preferring patient reassurance and training methods are successful in syncope prevention and help avoid the side effects and complications of pharmacological therapy or pacemaker implantation. These last two methods should be reserved for patients with the most severe symptoms of the disease.

  14. [The therapeutic approach to drug addicts].

    Science.gov (United States)

    Bucher, R E; Costa, P F

    1985-06-01

    Difficulties of biological, psychological, social and legal nature may be seen involved in the treatment of drug-addict persons. In this study, the major models used in the treatment are analysed, so as so one may arrived at a new model which will better integrate the various factors involved. The major models may be brought down to three: the medical psychiatric model which emphasizes the biological dependency on drugs and which equates drug addiction and "mental illness"; the behavioristic model which utilizes directive conditioning and desensitizing techniques, as well as educational and suggestional means, in order to determine new kinds of behavior; the relational model which takes origin from psychoanalysis and the systemic approach and sponsors a non-directive treatment of the drug-addict through the exploration and work on his personal and social unconscious conflicts, drive and desires, as well as his self-destructive tendencies. To assure the drug-addict a way to assume responsibility for his own behavior and to be free by respecting other people's rights, it is necessary to elaborate an integrative model of treatment which will consider also the anthropological specificity of the problems, referring also to the Brazilian society.

  15. [Diagnostic and therapeutic approach to pancreatic trauma].

    Science.gov (United States)

    Vidali, Maria; Doulgerakis, George; Condilis, Nicolas; Karmiri, Eleni; Poygouras, Ihon; Papaioannoy, George; Ioannoy, Christos; Pierrakakis, Stefanos; Setakis, Nicolas

    2005-01-01

    The pancreatic trauma is rare, compared with the injuries of the other abdominal organs and occurs in 0.2-6 per cent of the cases of abdominal trauma. The aim of this essay is to demonstrate the Authors' experience in the treatment of five cases of pancreatic injury during the last five years, as well as to retrospect the contemporary bibliography, connected with the diagnostic and curative approach of the pancreatic trauma. The diagnosis of the pancreatic trauma is difficult and many times, late. In their experience of pancreatic trauma, the Authors ascertained the pancreatic injury during the laparotomy which was made in order to treat other abdominal injuries. The surgical techniques were chosen taking into account the extent of the injury, the detection and the existence of accompanying. Marginal resection of pancreas, splenectomy and drainage were applied to three patients, suture of the pancreas and drainage to one patient, drainage alone and treatment of synchronous rupture of the duodenum to one patient. The mortality was 0%. Came whereas the morbidity came basically on the seriousness of the accompanying injuries.

  16. Therapeutic Recreation in the Community: An Inclusive Approach. Second Edition

    Science.gov (United States)

    Carter, Marcia Jean; LeConey, Stephen P.

    2004-01-01

    The second edition of Therapeutic Recreation in the Community: An Inclusive Approach reflects the changing and evolving nature of recreation and health care services. A number of social, economic, and political directives and technological advancements have fostered recreation in the community for all individuals. Due in part to a rising awareness…

  17. Germ cell transplantation using sexually competent fish: an approach for rapid propagation of endangered and valuable germlines.

    Directory of Open Access Journals (Sweden)

    Sullip K Majhi

    Full Text Available The transplantation of germ cells into adult recipient gonads is a tool with wide applications in animal breeding and conservation of valuable and/or endangered species; it also provides a means for basic studies involving germ cell (GC proliferation and differentiation. Here we describe the establishment of a working model for xenogeneic germ cell transplantation (GCT in sexually competent fish. Spermatogonial cells isolated from juveniles of one species, the pejerrey Odontesthes bonariensis (Atherinopsidae, were surgically transplanted into the gonads of sexually mature Patagonian pejerrey O. hatcheri, which have been partially depleted of endogenous GCs by a combination of Busulfan (40 mg/kg and high water temperature (25 degrees C treatments. The observation of the donor cells' behavior showed that transplanted spermatogonial cells were able to recolonize the recipients' gonads and resume spermatogenesis within 6 months from the GCT. The presence of donor-derived gametes was confirmed by PCR in 20% of the surrogate O. hatcheri fathers at 6 months and crosses with O. bonariensis mothers produced hybrids and pure O. bonariensis, with donor-derived germline transmission rates of 1.2-13.3%. These findings indicate that transplantation of spermatogonial cells into sexually competent fish can shorten considerably the production time of donor-derived gametes and offspring and could play a vital role in germline conservation and propagation of valued and/or endangered fish species.

  18. THERAPEUTIC SUPPORT OF REALIZATION OF THE COMPETENCE APPROACH IN EDUCATION

    Directory of Open Access Journals (Sweden)

    Viktoriia A. Lykova

    2010-08-01

    Full Text Available The article analyses mechanisms of realization of the competence approach in education. Its therapeutic support actualizes factors of nonlinearity, processuality, subjectivity, conformity with nature, feedback in the educational environment. Behind each person there is a variety of tendencies, therefore to foresee or plan, «limit by standards» what exactly will be personally significant for a particular student in pedagogical interaction, is impossible. Therapeutic competence of teachers allows to realize individual learning pathways with support on a «fan of indicators» within a circle of competences.

  19. Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders.

    Science.gov (United States)

    Henriques, Bárbara J; Lucas, Tânia G; Gomes, Cláudio M

    2016-01-01

    Riboflavin, or vitamin B2, plays an important role in the cell as biological precursor of FAD and FMN, two important flavin cofactors which are essential for the structure and function of flavoproteins. Riboflavin has been used in therapeutic approaches of various inborn errors of metabolism, notably in metabolic disorders resulting either from defects in proteins involved in riboflavin metabolism and transport or from defects in flavoenzymes. The scope of this review is to provide an updated perspective of clinical cases in which riboflavin was used as a potential therapeutic agent in disorders affecting mitochondrial energy metabolism. In particular, we discuss available mechanistic insights on the role of riboflavin as a pharmacological chaperone for the recovery of misfolded metabolic flavoenzymes.

  20. Internet addiction neuroscientific approaches and therapeutical implications including smartphone addiction

    CERN Document Server

    Reuter, Martin

    2017-01-01

    The second edition of this successful book provides further and in-depth insight into theoretical models dealing with Internet addiction, as well as includes new therapeutical approaches. The editors also broach the emerging topic of smartphone addiction. This book combines a scholarly introduction with state-of-the-art research in the characterization of Internet addiction. It is intended for a broad audience including scientists, students and practitioners. The first part of the book contains an introduction to Internet addiction and their pathogenesis. The second part of the book is dedicated to an in-depth review of neuroscientific findings which cover studies using a variety of biological techniques including brain imaging and molecular genetics. The third part of the book focuses on therapeutic interventions for Internet addiction. The fourth part of the present book is an extension to the first edition and deals with a new emerging potential disorder related to Internet addiction – smartphone addicti...

  1. New therapeutic approaches for treatment of tularaemia: a review

    Directory of Open Access Journals (Sweden)

    Sandrine eBOISSET

    2014-03-01

    Full Text Available Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones, the tetracyclines and the aminoglycosides. Because no effective and safe vaccine is currently available, tularaemia prophylaxis following proven exposure to F. tularensis also relies on administration of antibiotics. A number of reasons make it necessary to search for new therapeutic alternatives: the potential toxicity of first-line drugs, especially in children and pregnant women; a high rate of treatment relapses and failures, especially for severe and/or suppurated forms of the disease; and the possible use of antibiotic-resistant strains in the context of a biological threat. This review presents novel therapeutic approaches that have been explored in recent years to improve tularaemia patients’ management and prognosis. First, the activities of newly available antibiotic compounds were evaluated against F. tularensis, including tigecycline (a glycylcycline, ketolides (telithromycin and cethromycin and fluoroquinolones (moxifloxacin, gatifloxacin, trovafloxacin and grepafloxacin. The liposome delivery of some antibiotics was evaluated. The effect of antimicrobial peptides against F. tularensis was also considered. Other drugs were evaluated for their ability to suppress the intracellular multiplication of F. tularensis. The effects of the modulation of the innate immune response (especially via TLR receptors on the course of F. tularensis infection were characterized. Another approach was the administration of specific antibodies to induce passive resistance to F. tularensis infection. All of these studies highlight the need to develop new therapeutic strategies to improve the management of patients with tularaemia. Many possibilities exist, some unexplored. Moreover, it is likely that new therapeutic alternatives that are effective against this intracellular pathogen could be, at least partially, extrapolated to other human pathogens.

  2. Mathematical models for therapeutic approaches to control HIV disease transmission

    CERN Document Server

    Roy, Priti Kumar

    2015-01-01

    The book discusses different therapeutic approaches based on different mathematical models to control the HIV/AIDS disease transmission. It uses clinical data, collected from different cited sources, to formulate the deterministic as well as stochastic mathematical models of HIV/AIDS. It provides complementary approaches, from deterministic and stochastic points of view, to optimal control strategy with perfect drug adherence and also tries to seek viewpoints of the same issue from different angles with various mathematical models to computer simulations. The book presents essential methods and techniques for students who are interested in designing epidemiological models on HIV/AIDS. It also guides research scientists, working in the periphery of mathematical modeling, and helps them to explore a hypothetical method by examining its consequences in the form of a mathematical modelling and making some scientific predictions. The model equations, mathematical analysis and several numerical simulations that are...

  3. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  4. Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

    Science.gov (United States)

    Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

    2017-01-01

    Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment.

    Science.gov (United States)

    Atkinson, Stuart P; Andreu, Zoraida; Vicent, María J

    2018-01-23

    Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies. We discuss the various "hurdles" that a given PT faces on its passage from the syringe to the tumor (and beyond), including the passage through the bloodstream, tumor targeting, tumor uptake and the intracellular release of the active agent. However, we also discuss other relevant concepts and new considerations in the field, which we hope will provide new insight into the possible applications of PT-related biomarkers.

  6. Triple negative breast cancer: new therapeutic approaches and BRCA status.

    Science.gov (United States)

    Guney Eskiler, Gamze; Cecener, Gulsah; Egeli, Unal; Tunca, Berrin

    2018-05-01

    Treatment of triple negative breast cancer (TNBC) is a clinically challenging problem due to intriguing clinical and pathologic features of TNBC and natural or induced resistance to existing therapies. However, a great understanding of features of TNBC particularly associated with BRCA mutations has led to the development of different therapeutic approaches. Besides, identification of TNBC subtypes contribute to investigation of the underlying molecular differences and development of new strategies for the treatment of TNBC patients. In this review, we discussed the definition and characteristic properties of TNBC. We summarized an up-to-date description of the reported clinical trials of novel targeted strategies especially PARP inhibitors (PARPi) due to novel and highly potent for the treatment of TNBC. Additionally, we reviewed published studies which investigated the prevalence and types of BRCA1/2 mutation in breast cancer patients to assess and draw attention of association of BRCA status with TNBC. Consequently, the definition subtype of TNBC has important predictive value for the development of new therapeutic agents in the treatment of TNBC. Additionally, the incidence and types of mutations in BRCA-related pathways may be affected by ethnic origin and contribute to the risk of developing TNBC. © 2018 APMIS. Published by John Wiley & Sons Ltd.

  7. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

    Science.gov (United States)

    Sortino, Maria A.; Salomone, Salvatore; Carruba, Michele O.; Drago, Filippo

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios. PMID:28642705

  8. OSTEOARTHRITIS: CURRENT CLINICAL CONCEPT AND SOME PROMISING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2018-01-01

    Full Text Available In recent years, there has been a trend toward changing the clinical concept of osteoarthritis (OA. This disease has been considered as an age-related disease and the long-term result of a current pathological process for a very long time. However, many experts are now inclined to consider it necessary to identify the early, pre-X-ray stage of OA, when adequate treatment may not only halt the progression, but also achieve the regression of joint structural changes. This review deals with a number of pathogenetic and clinical aspects of the early stages of OA, which are important for timely diagnosis and pathogenetic therapy choice. It also considers some therapeutic approaches, both a "classic" and recently actively discussed methods for using platelet-rich plasma and autologous chondrocyte transplantation.

  9. Control of Bovine Mastitis: Old and Recent Therapeutic Approaches.

    Science.gov (United States)

    Gomes, Fernanda; Henriques, Mariana

    2016-04-01

    Mastitis is defined as the inflammatory response resulting of the infection of the udder tissue and it is reported in numerous species, namely in domestic dairy animals. This pathology is the most frequent disease of dairy cattle and can be potentially fatal. Mastitis is an economically important pathology associated with reduced milk production, changes in milk composition and quality, being considered one of the most costly to dairy industry. Therefore, the majority of research in the field has focused on control of bovine mastitis and many efforts are being made for the development of new and effective anti-mastitis drugs. Antibiotic treatment is an established component of mastitis control programs; however, the continuous search for new therapeutic alternatives, effective in the control and treatment of bovine mastitis, is urgent. This review will provide an overview of some conventional and emerging approaches in the management of bovine mastitis' infections.

  10. Fetal stem cells and skeletal muscle regeneration: a therapeutic approach

    Directory of Open Access Journals (Sweden)

    Michela ePozzobon

    2014-08-01

    Full Text Available More than 40% of the body mass is represented by muscle tissue, which possesses the innate ability to regenerate after damage through the activation of muscle specific stem cell, namely satellite cells. Muscle diseases, in particular chronic degenerative state of skeletal muscle such as dystrophies, lead to a perturbation of the regenerative process, which causes the premature exhaustion of satellite cell reservoir due to continue cycles of degeneration/regeneration. Nowadays, the research is focused on different therapeutic approaches, ranging from gene and cell to pharmacological therapy, but still there is not a definitive cure in particular for genetic muscle disease. Taking this in mind, in this article we will give special consideration to muscle diseases and the use of fetal derived stem cells as new approach for therapy. Cells of fetal origin, from cord blood to placenta and amniotic fluid, can be easily obtained without ethical concern, expanded and differentiated in culture, and possess immunemodulatory properties. The in vivo approach in animal models can be helpful to study the mechanism underneath the operating principle of the stem cell reservoir, namely the niche, which holds great potential to understand the onset of muscle pathologies.

  11. Genome Editing: A New Approach to Human Therapeutics.

    Science.gov (United States)

    Porteus, Matthew

    2016-01-01

    The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

  12. Challenging and valuable

    NARCIS (Netherlands)

    Van Hal, J.D.M.

    2008-01-01

    Challenging and valuable Inaugural speech given on May 7th 2008 at the occasion of the acceptance of the position of Professor Sustainable Housing Transformation at the faculty of Architeeture of the Delft University of Technology by Prof. J.D.M. van Hal MSc PhD.

  13. Therapeutic Approaches to Delay the Onset of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Raj Kumar

    2011-01-01

    Full Text Available The key cytopathologies in the brains of Alzheimer's disease (AD patients include mitochondrial dysfunction and energy hypometabolism, which are likely caused by the accumulation of small aggregates of amyloid-β (Aβ peptides. Thus, targeting these two abnormalities of the AD brain may hold promising therapeutic value for delaying the onset of AD. In his paper, we discuss two potential approaches to delay the onset of AD. The first is the use of low dose of diaminophenothiazins (redox active agents to prevent mitochondrial dysfunction and to attenuate energy hypometabolism. Diaminophenothiazines enhance mitochondrial metabolic activity and heme synthesis, both key factors in intermediary metabolism of the AD brain.The second is to use the naturally occurring osmolytes to prevent the formation of toxic forms of Aβ and prevent oxidative stress. Scientific evidence suggests that both approaches may change course of the basic mechanism of neurodegeneration in AD. Osmolytes are brain metabolites which accumulate in tissues at relatively high concentrations following stress conditions. Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation without perturbing other cellular processes. Osmolytes may inhibit the formation of Aβ oligomers in vivo, thus preventing the formation of soluble oligomers. The potential significance of combining diaminophenothiazins and osmolytes to treat AD is discussed.

  14. Novel approach to cancer therapeutics using comparative cancer biology

    OpenAIRE

    Revi, Bhindu

    2018-01-01

    Developing personalized cancer therapies based on cancer genomics methodologies forms the basis for future cancer therapeutics. A genomics platform was developed based on canine cancer to produce a proof-of-concept for personalized genomics led therapeutic choices but also developing personalized therapeutics for canine cancer patients themselves. The platform identified the genetic state of a canine cancer patient within two drugable pathways; p53 and HSP90/IRF1. The former ge...

  15. Therapeutical Approach of Osteoporosis — a Multidisciplinary Issue

    Directory of Open Access Journals (Sweden)

    Camelia Gliga

    2013-08-01

    Full Text Available Osteoporosis is the most frequent systemic disease of the bone, that affects elderly, mainly women in menopause. It can be defined by lowering of bone mass and microarchitectural deterioration of the bone tissue, resulting in an increased bone fragility. Main complications of osteoporosis are fractures of the vertebrae, hips and forearm. In view of its large variety of causes and manifestations, diagnostic and therapeutical approach in osteoporosis represents a multidisciplinary issue. The accurate diagnosis of osteoporosis is based on a method that measures the bone mineral density, expressed by the T-score, using dual energy X-ray absorptiometry, so called DXA. Lately, in practice in order for establishing the risk of osteoporosis and osteoporotic fracture the FRAX tool is increasingly used (The Fracture Risk Assessment. Treatment of osteoporosis is complex involving non-pharmacological and pharmacological measures. Non-pharmacological methods include preventive measures like exercise, external hip protectors, increase of dietary intake of calcium, vitamin D and proteins, especially in elderly, over 65 years. Pharmacological measures are represented by different types of drugs, including biphosphonates, bone formation stimulatory drugs, agents with new mechanisms of action, hormone replacement therapy and they will be indicated only after a detailed clinical and paraclinical examination of the patient. Regardless of the chosen pharmacological measure, periodical follow-up of efficacy, side-effects and complications of antiosteoporotic treatment, by clinical examination and laboratory investigations targeting bone remodelling, is strongly indicated.

  16. Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

    Science.gov (United States)

    Zhang, Xi-Feng; Liu, Zhi-Guo; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. PMID:27649147

  17. Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

    Science.gov (United States)

    Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2014-01-01

    It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

  18. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

    Science.gov (United States)

    Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

    2017-01-01

    Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  19. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Mario Stampanoni Bassi

    2017-12-01

    Full Text Available Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS, structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  20. Endoscopic Therapeutic Approach for Dysplasia in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Sung Noh Hong

    2017-09-01

    Full Text Available Long-standing intestinal inflammation in patients with inflammatory bowel disease (IBD induces dysplastic change in the intestinal mucosa and increases the risk of subsequent colorectal cancer. The evolving endoscopic techniques and technologies, including dye spraying methods and high-definition images, have been replacing random biopsies and have been revealed as more practical and efficient for detection of dysplasia in IBD patients. In addition, they have potential usefulness in detailed characterization of lesions and in the assessment of endoscopic resectability. Most dysplastic lesions without an unclear margin, definite ulceration, non-lifting sign, and high index of malignant change with suspicion for lymph node or distant metastases can be removed endoscopically. However, endoscopic resection of dysplasia in chronic IBD patients is usually difficult because it is often complicated by submucosal fibrosis. In patients with dysplasias that demonstrate submucosa fibrosis or a large size (≥20 mm, endoscopic submucosal dissection (ESD or ESD with snaring (simplified or hybrid ESD is an alternative option and may avoid a colectomy. However, a standardized endoscopic therapeutic approach for dysplasia in IBD has not been established yet, and dedicated specialized endoscopists with interest in IBD are needed to fully investigate recent emerging techniques and technologies.

  1. Recovering valuable liquid hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Pier, M

    1931-06-11

    A process for recovering valuable liquid hydrocarbons from coking coal, mineral coal, or oil shale through treatment with hydrogen under pressure at elevated temperature is described. Catalysts and grinding oil may be used in the process if necessary. The process provides for deashing the coal prior to hydrogenation and for preventing the coking and swelling of the deashed material. During the treatment with hydrogen, the coal is either mixed with coal low in bituminous material, such as lean coal or active coal, as a diluent or the bituminous constituents which cause the coking and swelling are removed by extraction with solvents. (BLM)

  2. Renal denervation: a new therapeutic approach for resistant hypertension.

    Science.gov (United States)

    Cao, Longxing; Fu, Qiang; Wang, Binghui; Li, Zhiliang

    2014-01-01

    To review the advances in studies on renal denervation. References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Articles with keywords "renal denervation" and "resistant hypertension" were selected. Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

  3. Cognition As a Therapeutic Target in the Suicidal Patient Approach

    Science.gov (United States)

    da Silva, Antônio Geraldo; Malloy-Diniz, Leandro Fernandes; Garcia, Marina Saraiva; Figueiredo, Carlos Guilherme Silva; Figueiredo, Renata Nayara; Diaz, Alexandre Paim; Palha, António Pacheco

    2018-01-01

    The current considerations about completed suicides and suicide attempts in different cultures call the attention of professionals to this serious public health problem. Integrative approaches have shown that the confluence of multiple biological and social factors modulate various psychopathologies and dysfunctional behaviors, such as suicidal behavior. Considering the level of intermediate analysis, personality traits and cognitive functioning are also of great importance for understanding the suicide phenomenon. About cognitive factors, we can group them into cognitive schemas of reality interpretation and underlying cognitive processes. On the other hand, different types of primary cognitive alterations are related to suicidal behavior, especially those resulting from changes in frontostriatal circuits. Among such cognitive mechanisms can be highlighted the attentional bias for environmental cues related to suicide, impulsive behavior, verbal fluency deficits, non-adaptive decision-making, and reduced planning skills. Attentional bias consists in the effect of thoughts and emotions, frequently not conscious, about the perception of environmental stimuli. Suicidal ideation and hopelessness can make the patient unable to find alternative solutions to their problems other than suicide, biasing their attention to environmental cues related to such behavior. Recent research efforts are directed to assess the possible use of attention bias as a therapeutic target in patients presenting suicide behavior. The relationship between impulsivity and suicide has been largely investigated over the last decades, and there is still controversy about the theme. Although there is strong evidence linking impulsivity to suicide attempts. Effective interventions address to reduce impulsivity in clinical populations at higher risk for suicide could help in the prevention. Deficits in problem-solving ability also seem to be distorted in patients who attempt suicide. Understanding

  4. Cognition As a Therapeutic Target in the Suicidal Patient Approach

    Directory of Open Access Journals (Sweden)

    Antônio Geraldo da Silva

    2018-02-01

    Full Text Available The current considerations about completed suicides and suicide attempts in different cultures call the attention of professionals to this serious public health problem. Integrative approaches have shown that the confluence of multiple biological and social factors modulate various psychopathologies and dysfunctional behaviors, such as suicidal behavior. Considering the level of intermediate analysis, personality traits and cognitive functioning are also of great importance for understanding the suicide phenomenon. About cognitive factors, we can group them into cognitive schemas of reality interpretation and underlying cognitive processes. On the other hand, different types of primary cognitive alterations are related to suicidal behavior, especially those resulting from changes in frontostriatal circuits. Among such cognitive mechanisms can be highlighted the attentional bias for environmental cues related to suicide, impulsive behavior, verbal fluency deficits, non-adaptive decision-making, and reduced planning skills. Attentional bias consists in the effect of thoughts and emotions, frequently not conscious, about the perception of environmental stimuli. Suicidal ideation and hopelessness can make the patient unable to find alternative solutions to their problems other than suicide, biasing their attention to environmental cues related to such behavior. Recent research efforts are directed to assess the possible use of attention bias as a therapeutic target in patients presenting suicide behavior. The relationship between impulsivity and suicide has been largely investigated over the last decades, and there is still controversy about the theme. Although there is strong evidence linking impulsivity to suicide attempts. Effective interventions address to reduce impulsivity in clinical populations at higher risk for suicide could help in the prevention. Deficits in problem-solving ability also seem to be distorted in patients who attempt

  5. Clinical decision-making and therapeutic approaches in osteopathy - a qualitative grounded theory study.

    Science.gov (United States)

    Thomson, Oliver P; Petty, Nicola J; Moore, Ann P

    2014-02-01

    There is limited understanding of how osteopaths make decisions in relation to clinical practice. The aim of this research was to construct an explanatory theory of the clinical decision-making and therapeutic approaches of experienced osteopaths in the UK. Twelve UK registered osteopaths participated in this constructivist grounded theory qualitative study. Purposive and theoretical sampling was used to select participants. Data was collected using semi-structured interviews which were audio-recorded and transcribed. As the study approached theoretical sufficiency, participants were observed and video-recorded during a patient appointment, which was followed by a video-prompted interview. Constant comparative analysis was used to analyse and code data. Data analysis resulted in the construction of three qualitatively different therapeutic approaches which characterised participants and their clinical practice, termed; Treater, Communicator and Educator. Participants' therapeutic approach influenced their approach to clinical decision-making, the level of patient involvement, their interaction with patients, and therapeutic goals. Participants' overall conception of practice lay on a continuum ranging from technical rationality to professional artistry, and contributed to their therapeutic approach. A range of factors were identified which influenced participants' conception of practice. The findings indicate that there is variation in osteopaths' therapeutic approaches to practice and clinical decision-making, which are influenced by their overall conception of practice. This study provides the first explanatory theory of the clinical decision-making and therapeutic approaches of osteopaths. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Vectorization of Nucleic Acids for Therapeutic Approach: Tutorial Review.

    Science.gov (United States)

    Geinguenaud, Frederic; Guenin, Erwann; Lalatonne, Yoann; Motte, Laurence

    2016-05-20

    Oligonucleotides present a high therapeutic potential for a wide variety of diseases. However, their clinical development is limited by their degradation by nucleases and their poor blood circulation time. Depending on the administration mode and the cellular target, these macromolecules will have to cross the vascular endothelium, to diffuse through the extracellular matrix, to be transported through the cell membrane, and finally to reach the cytoplasm. To overcome these physiological barriers, many strategies have been developed. Here, we review different methods of DNA vectorization, discuss limitations and advantages of the various vectors, and provide new perspectives for future development.

  7. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.

    Science.gov (United States)

    Berner, Andre K; Kleinman, Mark E

    2016-01-01

    Recent data have revealed epigenetic derangements and subsequent chromatin remodeling as a potent biologic switch for chronic inflammation and cell survival which are important therapeutic targets in the pathogenesis of several retinal degenerations. Histone deacetylases (HDACs) are a major component of this system and serve as a unique control of the chromatin remodeling process. With a multitude of targeted HDAC inhibitors now available, their use in both basic science and clinical studies has widened substantially. In the field of ocular biology, there are data to suggest that HDAC inhibition may suppress neovascularization and may be a possible treatment for retinitis pigmentosa and dry age-related macular degeneration (AMD). However, the effects of these inhibitors on cell survival and chemokine expression in the chorioretinal tissues remain very unclear. Here, we review the multifaceted biology of HDAC activity and pharmacologic inhibition while offering further insight into the importance of this epigenetic pathway in retinal degenerations. Our laboratory investigations aim to open translational avenues to advance dry AMD therapeutics while exploring the role of acetylation on inflammatory gene expression in the aging and degenerating retina.

  8. Protein and Peptide in Drug Targeting and its Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Raj K. Keservani

    2015-09-01

    Full Text Available Aim: The main aim of this review article is to provide information like advantages of protein and peptides via different routes of drug administration, targeted to a particular site and its implication in drug delivery system. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the development of protein and peptide drug targeting as well as its therapeutic activity. Results: In recent years many researchers use protein and peptide as a target site of drug by a different delivery system. Proteins and peptides are used as specific and effective therapeutic agents, due to instability and side effects their use is complicated. Protein kinases are important regulators of most, if not all, biological processes. Abnormal activity of proteins and peptides has been implicated in many human diseases, such as diabetes, cancer and neurodegenerative disorders. Conclusions: It is concluded that the protein and peptide were used in drug targeting to specific site and also used in different diseased states like cancer, diabetes, immunomodulating, neurodegenerative effects and antimicrobial activity.

  9. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    Science.gov (United States)

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-19

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

  10. A diagnostic and therapeutic approach to primary burning mouth syndrome.

    Science.gov (United States)

    Moghadam-Kia, Siamak; Fazel, Nasim

    Primary burning mouth syndrome (BMS) is an oral mucosal disorder that is characterized by a chronic and often debilitating intraoral burning sensation for which no localized or systemic cause can be found. BMS most commonly affects postmenopausal women. The pathophysiology of primary BMS is not well understood. Diagnosing BMS can prove to be challenging. BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients. Most commonly used therapies include tricyclic antidepressants, α-lipoic acid, clonazepam, and cognitive-behavioral therapy. Clinical judgment, patient counseling, and monitoring of pain are important. Further research is required to assess the effectiveness of serotonin and newer serotonin-noradrenalin reuptake inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

  12. [Sleep disturbances in Parkinson's disease: characteristics, evaluation and therapeutic approaches].

    Science.gov (United States)

    Faludi, Béla; Janszky, József; Komoly, Sámuel; Kovács, Norbert

    2015-07-05

    Parkinson's disease is a well known representent of the movement disorder group of neurological disorders. The diagnosis of Parkinson's disease is based on specific symptoms and signs of movement abnormalities. In addition to classic motor symptoms, Parkinson's disease has characteristic non-motor features, and some of these emerges the classic signs. The authors discuss characteristics and therapeutic interventions in Parkinson's disease related sleep disturbances. The authors reviewed and summarised literature data on sleep disorders in Parkinson's disease published in the PubMed database up to January 2015. Sleep problems are important non-motor complains (insomnia, hypersomnia, REM behaviour disorder, sleep apnea and restless legs syndrome). The neurodegenerative process of the brain-stem, the effect of symptoms of Parkinson's disease on sleep and concomitant sleep disorders constitute the background of the patient's complains. Appropriate diagnosis and therapy of the consequential or concomitant sleep disorders in Parkinson's disease will help to improve the patient's quality of life.

  13. [Limitation of therapeutic effort: Approach to a combined view].

    Science.gov (United States)

    Bueno Muñoz, M J

    2013-01-01

    Over the past few decades, we have been witnessing that increasing fewer people pass away at home and increasing more do so within the hospital. More specifically, 20% of deaths now occur in an intensive care unit (ICU). However, death in the ICU has become a highly technical process. This sometimes originates excesses because the resources used are not proportionate related to the purposes pursued (futility). It may create situations that do not respect the person's dignity throughout the death process. It is within this context that the situation of the clinical procedure called "limitation of the therapeutic effort" (LTE) is reviewed. This has become a true bridge between Intensive Care and Palliative Care. Its final goal is to guarantee a dignified and painless death for the terminally ill. Copyright © 2012 Elsevier España, S.L. y SEEIUC. All rights reserved.

  14. Pathophysiological aspects and therapeutic approaches of tumoral osteolysis and hypercalcemia.

    Science.gov (United States)

    Bonjour, J P; Rizzoli, R

    1989-01-01

    Malignant tumors can affect the integrity of the skeletal tissue and the homeostasis of the two main components of bone mineral, calcium (Ca) and inorganic phosphate (Pi). Various tumoral cell products can increase bone resorption by influencing the number of osteoclasts and/or their activity. These tumoral products could act either directly on bone cells of the osteoblastic or osteoclastic lineages, or indirectly by influencing cells secreting osteotropic factors, such as interleukin-1, tumor necrosis factors, transforming growth factors, and colony-stimulating factor. Among the classical calciotropic hormones, 1,25-dihydroxyvitamin D3 could be implicated in lymphoma. In hypercalcemia of malignancy, an increase in bone resorption is observed in most patients. However, in many cases an increased tubular reabsorption of Ca has been documented as well. This phenomenon when present after adequate rehydration is probably due to the secretion by the tumoral cells of a parathyroid hormone-related peptide (PTHrP). This factor has been recently identified as a protein containing 141 amino acids. This protein or some very close analogs have been shown to be secreted by lung, kidney and also breast carcinoma. Besides increasing bone resorption and stimulating tubular reabsorption of Ca, PTHrP also selectively decreases the tubular reabsorption of Pi, an action that may explain the hypophosphatemia observed in some types of neoplasm. Therapeutically, administration of antiresorbing agents such as clodronate or other bisphosphonates can normalize the increased osteolysis and, if present, the associated elevation in the plasma level of Ca in most cancer patients. However in some cases, wherein the prevailing hypercalcemic mechanism is due to an enhancement in the tubular reabsorption of Ca, other therapeutic means should be associated with the antiosteolytic bisphosphonate therapy.

  15. Therapeutic approaches for treating hemophilia A using embryonic stem cells.

    Science.gov (United States)

    Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko

    2016-06-01

    Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  16. Synthetic Lethal Therapeutic Approaches for ARID1A-Mutated Ovarian Cancer

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-16-1-0496 TITLE: Synthetic lethal therapeutic approaches for ARID1A-mutated ovarian cancer PRINCIPAL INVESTIGATOR: Rugang...AND SUBTITLE Synthetic lethal therapeutic approaches for ARID1A-mutated ovarian cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0496 5c...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological

  17. Bioinformatics approaches for identifying new therapeutic bioactive peptides in food

    Directory of Open Access Journals (Sweden)

    Nora Khaldi

    2012-10-01

    Full Text Available ABSTRACT:The traditional methods for mining foods for bioactive peptides are tedious and long. Similar to the drug industry, the length of time to identify and deliver a commercial health ingredient that reduces disease symptoms can take anything between 5 to 10 years. Reducing this time and effort is crucial in order to create new commercially viable products with clear and important health benefits. In the past few years, bioinformatics, the science that brings together fast computational biology, and efficient genome mining, is appearing as the long awaited solution to this problem. By quickly mining food genomes for characteristics of certain food therapeutic ingredients, researchers can potentially find new ones in a matter of a few weeks. Yet, surprisingly, very little success has been achieved so far using bioinformatics in mining for food bioactives.The absence of food specific bioinformatic mining tools, the slow integration of both experimental mining and bioinformatics, and the important difference between different experimental platforms are some of the reasons for the slow progress of bioinformatics in the field of functional food and more specifically in bioactive peptide discovery.In this paper I discuss some methods that could be easily translated, using a rational peptide bioinformatics design, to food bioactive peptide mining. I highlight the need for an integrated food peptide database. I also discuss how to better integrate experimental work with bioinformatics in order to improve the mining of food for bioactive peptides, therefore achieving a higher success rates.

  18. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    International Nuclear Information System (INIS)

    Ando, Kosei; Heymann, Marie-Françoise; Stresing, Verena; Mori, Kanji; Rédini, Françoise; Heymann, Dominique

    2013-01-01

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies

  19. Therapeutic approach to Gradenigo's syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Aspris Andreas

    2010-05-01

    Full Text Available Abstract Introduction Traditional management of Gradenigo's syndrome requires aggressive and radical surgery without any attempt to preserve hearing. Recent reports, however, describe a successful outcome after conservative surgical intervention without labyrinthectomy. A similar outcome has also been reported in patients who were only prescribed with antibiotics and did not undergo myringotomy. Case presentation We report the case of a 24-year-old Caucasian Greek woman with Gradenigo's syndrome who was treated by draining her petrous apex via an infralabyrithine approach between her posterior semicircular canal and the jugular bulb. Her inner ear was not sacrificed during the procedure. She presented pre-operatively with ipsilateral conductive hearing loss, which recovered completely four weeks after the surgery. Conclusions Patients with Gradenigo's syndrome may be successfully treated with a combination of long-term permanent drainage and ventilation of the apical cells with corresponding hearing preservation. This can be achieved via a combination of transmastoid, infralabyrinthine and suprajugular approaches, if such would be allowed by the anatomy of the region or if there is enough space between the posterior semicircular canal and the jugular bulb.

  20. [Cormorbidity in multiple sclerosis and its therapeutic approach].

    Science.gov (United States)

    Estruch, Bonaventura Casanova

    2014-12-01

    Multiple sclerosis (MS) is a long-term chronic disease, in which intercurrent processes develop three times more frequently in affected individuals than in persons without MS. Knowledge of the comorbidity of MS, its definition and measurement (Charlson index) improves patient management. Acting on comorbid conditions delays the progression of disability, which is intimately linked to the number of concurrent processes and with health states and habits. Moreover, the presence of comorbidities delays the diagnosis of MS, which in turn delays the start of treatment. The main comorbidity found in MS includes other autoimmune diseases (thyroiditis, systemic lupus erythematosus, or pemphigus) but can also include general diseases, such as asthma or osteomuscular alterations, and, in particular, psychiatric disturbances. All these alterations should be evaluated with multidimensional scales (Disability Expectancy Table, DET), which allow more accurate determination of the patient's real clinical course and quality of life. These scales also allow identification of how MS, concurrent and intercurrent processes occurring during the clinical course, and the treatment provided affect patients with MS. An overall approach to patients' health status helps to improve quality of life. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  1. Physical urticarias: mast cell disfunction. Preventive, diagnostic and therapeutical approach

    Directory of Open Access Journals (Sweden)

    Mario Geller

    2007-09-01

    Full Text Available Objective: To present and discuss the current classification of physicalurticarias based on immunologic and pathophysiological mechanisms.To describe clinical symptoms, triggering and worsening factors,different diagnostic tools, and to list the available pharmacologicaltherapeutic approaches as well as the methods of physicaldesensitization. Methods: The literature search was carried out usingMedline. Forty studies were evaluated including case-control series,meta-analyses, case reports and reviews in the English language. Thekeywords used were physical urticarias, classification, and physicaldesensitization. A didactic diagnostic classification of differentgroups of physical urticarias was made, as well as a description ofthe several modalities of these dermatatologic conditions causedby physical stimuli, as localized or diffuse, classical or atypical,acquired or familial, with or without IgE involvement. The geneticpredisposing factors were determined. Results: Physical urticaria isdue to mast cell dysfunction with lowered threshold for the releaseof cytoplasmic anaphylactic mediators triggered by physical factors.These precipitating environmental physical factors include cold, heat,mechanical stimuli, exercises, exposure to sunlight and skin contactwith water. Conclusions: Physical urticarias occur in approximately17% of chronic urticaria patients and different forms may coexist inthe same individual. Treatments include prevention, antihistamines(classical and non-sedating presentations and, occasionally,corticosteroids, dapsone and other anti-inflammatory drugs, and thepotential use of specific physical desensitization.

  2. Novel diagnostic approaches and biological therapeutics for intrinsic asthma

    Directory of Open Access Journals (Sweden)

    Vennera MC

    2014-07-01

    Full Text Available María del Carmen Vennera,1–3 César Picado1–3 1Department of Pneumology and Respiratory Allergy, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; 2Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Spain; 3Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES, Spain Abstract: Intrinsic asthma has been considered as a specific disease entity for a long time, although many controversies have emerged in relation to this concept. Of note, not finding specific allergen sensitization in an asthmatic patient neither excludes an allergic component nor the essential role that immunoglobulin E may play in asthma. The diagnostic approach should be similar in any patient suspected to have asthma. The atopic status is one among many other questions. Omalizumab, the only monoclonal anti-immunoglobulin E antibody commercialized for asthma, should be tried in patients with uncontrolled severe asthma independent of their atopic status. Keywords: nonatopic asthma, immunoglobulin E, omalizumab

  3. Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

    Science.gov (United States)

    Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

    2017-10-01

    Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Endovascular Therapeutic Approaches for Acute Superior Mesenteric Artery Occlusion

    International Nuclear Information System (INIS)

    Acosta, S.; Sonesson, B.; Resch, T.

    2009-01-01

    The purpose of this study was to characterize the outcome of attempted endovascular intervention in patients with acute embolic or thrombotic superior mesenteric artery (SMA) occlusion. The records of 21 patients during a 3-year period between 2005 and 2008 were retrieved from the in-hospital registry. The first group included 10 patients (6 women and 4 men; median age 78 years) with acute embolic occlusion of the SMA. The median duration of symptoms from symptom onset to angiography was 30 hours (range 6 to 120). Synchronous emboli (n = 12) occurred in 6 patients. Embolus aspiration was performed in 9 patients, and 7 of these had satisfactory results. Complementary local thrombolysis was successful in 2 of 3 patients. Residual emboli were present at completion angiography in all 7 patients who underwent successful aspiration embolectomy, and bowel resection was necessary in only 1 of these patients. One serious complication occurred because of a long SMA dissection. The in-hospital survival rate was 90% (9 of 10 patients). The second group included 11 patients (10 women and 1 man; median age 68 years) with atherosclerotic acute SMA occlusions. The median time of symptom duration before intervention was 97 hours (range 17 to 384). The brachial, femoral, and SMA routes were used in 6, 7, and 5 patients, respectively. SMA stenting was performed through an antegrade (n = 7) or retrograde (n = 3) approach. Bowel resection was necessary in 4 patients. No major complications occurred. The in-hospital survival rate was 82% (9 of 11 patients). Endovascular therapy of acute SMA occlusion provides a good alternative to open surgery.

  5. Aligning Animal Models of Clinical Germinal Matrix Hemorrhage, From Basic Correlation to Therapeutic Approach.

    Science.gov (United States)

    Lekic, Tim; Klebe, Damon; Pichon, Pilar; Brankov, Katarina; Sultan, Sally; McBride, Devin; Casel, Darlene; Al-Bayati, Alhamza; Ding, Yan; Tang, Jiping; Zhang, John H

    2017-01-01

    Germinal matrix hemorrhage is a leading cause of mortality and morbidity from prematurity. This brain region is vulnerable to bleeding and re-bleeding within the first 72 hours of preterm life. Cerebroventricular expansion of blood products contributes to the mechanisms of brain injury. Consequences include lifelong hydrocephalus, cerebral palsy, and intellectual disability. Unfortunately little is known about the therapeutic needs of this patient population. This review discusses the mechanisms of germinal matrix hemorrhage, the animal models utilized, and the potential therapeutic targets. Potential therapeutic approaches identified in pre-clinical investigations include corticosteroid therapy, iron chelator administration, and transforming growth factor-β pathway modulation, which all warrant further investigation. Thus, effective preclinical modeling is essential for elucidating and evaluating novel therapeutic approaches, ahead of clinical consideration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

    Science.gov (United States)

    Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

    2017-01-06

    Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

  7. Rasch-family models are more valuable than score-based approaches for analysing longitudinal patient-reported outcomes with missing data.

    Science.gov (United States)

    de Bock, Élodie; Hardouin, Jean-Benoit; Blanchin, Myriam; Le Neel, Tanguy; Kubis, Gildas; Bonnaud-Antignac, Angélique; Dantan, Étienne; Sébille, Véronique

    2016-10-01

    The objective was to compare classical test theory and Rasch-family models derived from item response theory for the analysis of longitudinal patient-reported outcomes data with possibly informative intermittent missing items. A simulation study was performed in order to assess and compare the performance of classical test theory and Rasch model in terms of bias, control of the type I error and power of the test of time effect. The type I error was controlled for classical test theory and Rasch model whether data were complete or some items were missing. Both methods were unbiased and displayed similar power with complete data. When items were missing, Rasch model remained unbiased and displayed higher power than classical test theory. Rasch model performed better than the classical test theory approach regarding the analysis of longitudinal patient-reported outcomes with possibly informative intermittent missing items mainly for power. This study highlights the interest of Rasch-based models in clinical research and epidemiology for the analysis of incomplete patient-reported outcomes data. © The Author(s) 2013.

  8. Insomnia in childhood and adolescence: clinical aspects, diagnosis, and therapeutic approach

    Directory of Open Access Journals (Sweden)

    Magda Lahorgue Nunes

    2015-11-01

    Conclusions: Insomnia complaints in children and adolescents should be taken into account and appropriately investigated by the pediatrician, considering the association with several comorbidities, which must also be diagnosed. The main causes of insomnia and triggering factors vary according to age and development level. The therapeutic approach must include sleep hygiene and behavioral techniques and, in individual cases, pharmacological treatment.

  9. Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches?

    Science.gov (United States)

    Phillip, Harris; Okewole, Idris; Chilaka, Victor

    2014-06-01

    Urethral pain syndrome has had several sobriquets, which have led to much confusion over the existence of this pathological condition and the useful options in the care of the afflicted patient. Our aim was to explore the proposed etiologies of this syndrome, and to provide a critical analysis of each proposed etiology and present a balanced argument on the plausibility of the proposed etiology and therapeutic approaches. We carried out an English language electronic search in the following databases: Medline, Embase, Amed, Cinahl, Pubmed, Cochrane Library, Trip Database and SUMSearch using the following search terms: urethral syndrome, urethral diseases, urethra, urologic diseases etiology/etiology, presentation, treatment, outcome, therapeutics and treatment from 1951 to 2011. In excess of 200 articles were recovered. With the clearly defined objectives of analyzing the proposed etiologies and therapeutic regimes, two author(s) (HP and IO) perused the abstracts of all the recovered articles, selecting those that addressed the etiologies and therapeutic approaches to treating the urethral pain syndrome. The number of articles was reduced to 25. The full text of all 25 articles were retrieved and reviewed. Through the present article, we hope to elucidate the most probable etiology of this condition whilst simultaneously, advance a logical explanation for the apparent success in the treatment of this condition using a range of different therapeutic modalities. We have carried out a narrative review, which we hope will reduce some of the confusion around this clinical entity by combining the known facts about the disease. © 2014 The Japanese Urological Association.

  10. Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

    Directory of Open Access Journals (Sweden)

    Maria Giuseppina Cefalo

    2016-01-01

    Full Text Available Many central nervous system (CNS diseases including stroke, spinal cord injury (SCI, and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

  11. Recovering valuable shale oils, etc

    Energy Technology Data Exchange (ETDEWEB)

    Engler, C

    1922-09-26

    A process is described for the recovery of valuable shale oils or tars, characterized in that the oil shale is heated to about 300/sup 0/C or a temperature not exceeding this essentially and then is treated with a solvent with utilization of this heat.

  12. Narrative Financial Therapy: Integrating a Financial Planning Approach with Therapeutic Theory

    Directory of Open Access Journals (Sweden)

    Megan A. McCoy

    2014-03-01

    Full Text Available The article serves as one of the first attempts to develop an integrated theoretical approach to financial therapy that can be used by practitioners from multiple disciplines. The presented approach integrates the components of the six-step financial planning process with components of empirically-supported therapeutic methods. This integration provides the foundation for a manualized approach to financial therapy, shaped by the writings of narrative theorists and select cognitive-behavioral interventions that can be used both by mental health and financial professionals.

  13. The approach of cancer related fatigue in rehabilitation medicine: Part II – Therapeutic interventions

    Directory of Open Access Journals (Sweden)

    Salca Amalia

    2015-09-01

    Full Text Available Starting with patient’ diagnose and continuing throughout the treatment and thereafter, cancer-related fatigue (CRF is a distressing and disabling symptom, highly prevalent across the cancer continuum2. This is a review article mainly focusing on the rehabilitation objectives and interventions in CRF, and implementation issues, according to the report of an NCCN member institution4. Implementation is the most problematic, considering the large number of patients to whom it is addressed to and the variety of pathologies within this group of patients. The onset of CRF is difficult to establish, because of the limitations of reporting this symptom4, but it is a valuable predictor in prognosis. The main interventions in rehabilitation applicable to these patients are discussed in correlation to the objectives of each phase of therapeutic management in cancer: pre-operatory, before, during or after radio and/or chemotherapy Conclusion: Rehabilitation interventions should be applied to all patients diagnosed with cancer, according to their phase of oncologic treatment and the objectives. This should be practiced as preventive measure, but as a therapeutic one to, considering the high incidence of CFR before diagnose.

  14. Epigenetics: A novel therapeutic approach for the treatment of Alzheimer’s disease

    Science.gov (United States)

    Adwan, Lina; Zawia, Nasser H.

    2013-01-01

    Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field. PMID:23562602

  15. ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.

    Science.gov (United States)

    Bonafede, Roberta; Mariotti, Raffaella

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.

  16. [From tic disorders to Tourette syndrome: current data, comorbidities, and therapeutic approach in children].

    Science.gov (United States)

    Fourneret, P; Desombre, H; Broussolle, E

    2014-06-01

    Motor tics are frequently observed in children during development. Usually transient and benign, they can become chronic over time, join various morbid disorders (vocal tics, attention deficit and hyperactivity disorder, and obsessive-compulsive disorders) and move toward genuine Tourette syndrome. In this case, it will be necessary to prevent impacts - mainly in terms of quality of life and emotional and relational problems - using a global therapeutic strategy combining psychoeducational approaches with appropriate medication. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

    International Nuclear Information System (INIS)

    Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

    2011-01-01

    Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

  18. Preparing valuable hydrocarbons by hydrogenation

    Energy Technology Data Exchange (ETDEWEB)

    Pier, M

    1930-08-22

    A process is described for the preparation of valuable hydrocarbons by treatment of carbonaceous materials, like coal, tars, minerals oils, and their distillation and conversion products, and for refining of liquid hydrocarbon mixture obtained at raised temperature and under pressure, preferably in the presence of catalysts, by the use of hydrogen-containing gases, purified and obtained by distilling solid combustibles, characterized by the purification of the hydrogen-containing gases being accomplished for the purpose of practically complete removal of the oxygen by heating at ordinary or higher pressure in the presence of a catalyst containing silver and oxides of metals of group VI of the periodic system.

  19. Energy threat to valuable land

    International Nuclear Information System (INIS)

    Caufield, C.

    1982-01-01

    Having considered the varying estimates of future UK energy requirements which have been made, the impact on the environment arising from the use of valuable sites for energy production is examined. It is shown that energy installations of all kinds clash with areas of natural beauty or ecological importance. As an example, a recent investigation of potential sites for nuclear power stations found that most of them were on or next to sites of special scientific interest, and other areas officially designated to be regarded as special or to be protected in some way. (U.K.)

  20. Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

    Science.gov (United States)

    Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

    2018-03-01

    Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  1. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2016-01-01

    Full Text Available Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.

  2. Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

    Science.gov (United States)

    Kim, Ye-Ram; Yang, Chul-Su

    2017-09-28

    Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

  3. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

    2011-03-31

    Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

  4. Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

    Directory of Open Access Journals (Sweden)

    Fiebich Bernd L

    2011-03-01

    Full Text Available Abstract Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix" are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA, paracetamol (acetaminophen and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden

  5. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Science.gov (United States)

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  6. Novel therapeutic approach targeting the HIF-HRE system in the kidney.

    Science.gov (United States)

    Nangaku, Masaomi

    2009-01-01

    Recent studies emphasize the role of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease. Therefore, therapeutic approaches which target the chronic hypoxia should prove effective against a broad range of renal diseases. Many of hypoxia-triggered protective mechanisms are hypoxia inducible factor (HIF)-dependent. Although HIF-1 alpha and HIF-2 alpha share both structural and functional similarity, they have different localization and can contribute in a non-redundant manner. While gene transfer of constitutively active HIF has been shown effective, pharmacological approaches to activate HIF are more desirable. Oxygen-dependent activation of prolyl hydroxylases (PHD) regulates the amount of HIF by degradation of this transcription factor. Therefore, PHD inhibitors have been the focus of recent studies on novel strategies to stabilize HIF. Cobalt is one of the inhibitors of PHD, and stimulation of HIF with cobalt is effective in a variety of kidney disease models. Furthermore, crystal structures of the catalytic domain of human prolyl hydroxylase 2 have been clarified recently. The structure aids in the design of PHD selective inhibitors for the treatment of hypoxic tissue injury. Current advance has elucidated the detailed mechanism of hypoxia-induced transcription, giving hope for the development of novel therapeutic approaches against hypoxia.

  7. ABO-incompatible blood transfusion and invasive therapeutic approaches during pediatric cardiopulmonary bypass.

    Science.gov (United States)

    Aliç, Yasin; Akpek, Elif A; Dönmez, Asli; Ozkan, Süleyman; Perfusionist, Güray Yener; Aslamaci, Sait

    2008-10-01

    Human error has been identified as a major source of ABO-incompatible blood transfusion which most often results from blood being given to the wrong patient. We present a case of inadvertent administration of ABO-incompatible blood to a 6-mo-old child who underwent congenital heart surgery and discuss the use of invasive therapeutic approaches. Invasive techniques included total circulatory arrest and large-volume exchange transfusion, along with conventional ultrafiltration and plasmapheresis, which could all be performed rapidly and effectively. The combination of standard pharmacologic therapies and alternative invasive techniques after a massive ABO-incompatible blood transfusion led to a favorable outcome in our patient.

  8. A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

    Science.gov (United States)

    Williams, Todd O.

    2012-01-01

    A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

  9. Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases.

    Science.gov (United States)

    Halilbasic, Emina; Steinacher, Daniel; Trauner, Michael

    2017-01-01

    Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on "Bile Acids in Health and Disease" held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC. © 2017 S. Karger AG, Basel.

  10. Novel Therapeutic Approaches to the Treatment of Chronic Abdominal Visceral Pain

    Directory of Open Access Journals (Sweden)

    Franca Patrizi

    2006-01-01

    Full Text Available Chronic abdominal visceral pain (CAVP has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS, might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

  11. MVT a most valuable theorem

    CERN Document Server

    Smorynski, Craig

    2017-01-01

    This book is about the rise and supposed fall of the mean value theorem. It discusses the evolution of the theorem and the concepts behind it, how the theorem relates to other fundamental results in calculus, and modern re-evaluations of its role in the standard calculus course. The mean value theorem is one of the central results of calculus. It was called “the fundamental theorem of the differential calculus” because of its power to provide simple and rigorous proofs of basic results encountered in a first-year course in calculus. In mathematical terms, the book is a thorough treatment of this theorem and some related results in the field; in historical terms, it is not a history of calculus or mathematics, but a case study in both. MVT: A Most Valuable Theorem is aimed at those who teach calculus, especially those setting out to do so for the first time. It is also accessible to anyone who has finished the first semester of the standard course in the subject and will be of interest to undergraduate mat...

  12. The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy.

    Science.gov (United States)

    Hosseini, Maryam; Haji-Fatahaliha, Mostafa; Jadidi-Niaragh, Farhad; Majidi, Jafar; Yousefi, Mehdi

    2016-06-01

    Cancer is one of the most important causes of death all over the world, which has not yet been treated efficiently. Although several therapeutic approaches have been used, some side effects such as toxicity and drug resistance have been observed in patients, particularly with chemotherapy. The nanoparticle-mediated drug delivery systems (DDS) have a great potential to improve cancer treatment by transferring therapeutic factors directly to the tumor site. Such a treatment significantly decreases the adverse effects associated with cancer therapy on healthy tissues. Two main strategies, including passive and active methods, have been considered to be effective techniques which can target the drugs to the tumor sites. The current review sheds some light on the place of nanotechnology in cancer drug delivery, and introduces nanomaterials and their specific characteristics that can be used in tumor therapy. Moreover, passive and active targeting approaches focus on antibodies, particularly single chain variable fragments (scFv), as a novel and important ligand in a drug delivery system.

  13. Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Zhong-Cheng Xin

    2016-01-01

    Full Text Available Transplanted stem cells (SCs, owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED. However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1 SC niche and SC biological features in vitro; (2 localization and mobilization of endogenous SCs; (3 existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.

  14. Do stone size and impaction influence therapeutic approach to proximal ureteral stones?

    Directory of Open Access Journals (Sweden)

    Radulović Slobodan

    2009-01-01

    Full Text Available Background/Aim. Primary therapeutic approach to lumbar ureteral stones is still contraversial. The aim of the study was to investigate the influence of stone impaction and size on the effectiveness of proximal ureteral stone lithotripsy. Methods. A total of 123 patients with proximal ureteral stones were investigated in this prospective study performed in a 10- month period. The patients were divided into the group I - 86 patients treated with extracorporeal shock wave lithotripsy (ESWL and the group II - 37 patients treated with 'Swiss' Lithoclast. In the group I, 49 stones (57% were classified as impacted, while 20 stones (23.3% were larger than 100 mm2. In the group II, 26 stones (70.3% were impacted, and 11 stones (29.7% were larger than 100 mm2. Stones were defined as impacted by the radiographic, echosonographic as well as endoscopic findings in the group II of patients. Stone size was presented in mm2. Chemical composition of stones were almost the same in both groups of the patients. Results. Generally, there was no statistically significant difference in the treatment success between the groups. However, stones larger than 100 mm2 were statistically more successfully treated endoscopically, while there was no statistical difference in the treatment success of impacted stones between these two groups. Conclusion. ESWL can by considered as primary first therapeutic approach in treatment of all proximal ureteral stones except for stones larger than 100 mm2 that should primarily be treated endoscopically.

  15. Consideration of therapeutic approach to advanced colorectal cancer in elderly patients

    Directory of Open Access Journals (Sweden)

    Yasuhiro Inoue

    2014-02-01

    Full Text Available Colorectal cancer (CRC is predominantly a disease of elderly and is a major cause of morbidity and mortality in the elderly population. The increased availability of treatment options for CRC has made it more difficult for clinicians to decide on the optimal therapeutic approach in elderly patients, because of the potential for poorer outcomes due to an increased burden of comorbidities, functional dependency, and limited life expectancy. It is necessary to determine which elderly patients are likely to benefit from active cancer therapy, and the establishment of treatment markers for multimodality approaches is eagerly awaited. Elderly cancer patients are at risk of exposure to various intrinsic inflammatory mediators, such as tumor-generating cytokines and surgery-induced pro-inflammatory cytokines. It is therefore important to understand the immunological changes occurring in the elderly and to adjust treatment strategies accordingly to reduce the morbidity and mortality associated with multimodality therapy for CRC that induce systemic inflammation. Several inflammation-based factors such as the Glasgow Prognostic Score (GPS may reflect the balance between tumor progression and host-related immunity, especially in elderly CRC patients. Appropriate selection criteria for multimodality therapy in elderly CRC patients may include not only tumor characteristics, but also host- and/or treatment-related factors such as comorbidities or surrogate markers using inflammation-based factors.----------------------------------------------Cite this article as: Inoue Y, Toiyama Y, Tanaka K, Mohri Y, Kusunoki M. Consideration of therapeutic approach to advanced colorectal cancer in elderly patients. Int J Cancer Ther Oncol 2014; 2(1:02014.DOI: http://dx.doi.org/10.14319/ijcto.0201.4

  16. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  17. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  18. Retrospective analysis of 104 histologically proven adult brainstem gliomas: clinical symptoms, therapeutic approaches and prognostic factors

    International Nuclear Information System (INIS)

    Reithmeier, Thomas; Kuzeawu, Aanyo; Hentschel, Bettina; Loeffler, Markus; Trippel, Michael; Nikkhah, Guido

    2014-01-01

    Adult brainstem gliomas are rare primary brain tumors (<2% of gliomas). The goal of this study was to analyze clinical, prognostic and therapeutic factors in a large series of histologically proven brainstem gliomas. Between 1997 and 2007, 104 patients with a histologically proven brainstem glioma were retrospectively analyzed. Data about clinical course of disease, neuropathological findings and therapeutic approaches were analyzed. The median age at diagnosis was 41 years (range 18-89 years), median KPS before any operative procedure was 80 (range 20-100) and median survival for the whole cohort was 18.8 months. Histopathological examinations revealed 16 grade I, 31 grade II, 42 grade III and 14 grade IV gliomas. Grading was not possible in 1 patient. Therapeutic concepts differed according to the histopathology of the disease. Median overall survival for grade II tumors was 26.4 months, for grade III tumors 12.9 months and for grade IV tumors 9.8 months. On multivariate analysis the relative risk to die increased with a KPS ≤ 70 by factor 6.7, with grade III/IV gliomas by the factor 1.8 and for age ≥ 40 by the factor 1.7. External beam radiation reduced the risk to die by factor 0.4. Adult brainstem gliomas present with a wide variety of neurological symptoms and postoperative radiation remains the cornerstone of therapy with no proven benefit of adding chemotherapy. Low KPS, age ≥ 40 and higher tumor grade have a negative impact on overall survival

  19. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update

    Directory of Open Access Journals (Sweden)

    Pragya Tiwari

    2015-01-01

    Full Text Available Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management.

  20. Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

    Science.gov (United States)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

    2016-11-01

    In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially misfolded intermediates aggregate via the interaction with the complementary intermediates and consequently enhance oligomers formation that grows into fibrils and proto-fibrils. The amyloid fibrils for example, accumulate in the brain and central nervous system (CNS) as amyloid deposits in the Parkinson's disease (PD), Alzheimer's disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other neurodegenerative diseases. Treatment of such misfolding maladies is considered as one of the most important challenges of the 21st century. Currently, several treatments strategies have been and are being discovered. These therapeutic interventions partly reversed or prevented the pathological state. More recently, a new approach was discovered, which employs nanobodies that targets multisteps in fibril formation pathway that may possibly completely cure these misfolding diseases. Keeping the above views in mind in the current review, we have comprehensively discussed the different mechanisms underlying protein misfolding thereby leading to diseases conditions and their therapeutic interventions.

  1. Nano-particles for therapeutical purposes: an innovative approach for the radiotherapy of cancer

    International Nuclear Information System (INIS)

    Borghi, E.; Said, P.; Pottier, A.; Levy, L.

    2010-01-01

    Nano-technology can be used to manage and assemble substances in unprecedented ways in the history of products for human health. Underlying this revolution are the possibilities for using new therapeutic processes and separating a drug's various functions (distribution, effects, etc.). This is not possible with classical drugs. Nano-medicine has made it possible to develop new approaches to treating cancer, by using nano-particles with physical effects at the scale of the malignant cell. Hard metallic oxide nano-particles have been designed so that they can play a therapeutic role when activated by x-rays. The x-rays irradiation will free electrons from the metallic oxide, these electrons will lose energy through collisions with water molecules and will create free radicals in the cells. These free radicals are very reactive and will damage the covalent bounds of the molecules located around the nano-particles. Clinical tests on man are expected to begin very soon. These 'x-ray-activable' nano-particles might set off a revolution in the practice of radiotherapy for destroying or controlling malignant tumors

  2. Medicinal plants growing in the Judea region: network approach for searching potential therapeutic targets

    Directory of Open Access Journals (Sweden)

    Arie Budovsky

    2012-09-01

    Full Text Available Plants growing in the Judea region are widely used in traditional medicine of the Levant region. Nevertheless, they have not so far been sufficiently analyzed and their medicinal potential has not been evaluated. This study is the first attempt to fill the gap in the knowledge of the plants growing in the region. Comprehensive data mining of online botanical databases and peer-reviewed scientific literature including ethno-pharmacological surveys from the Levant region was applied to compile a full list of plants growing in the Judea region, with the focus on their medicinal applications. Around 1300 plants growing in the Judea region were identified. Of them, 25% have medicinal applications which were analyzed in this study. Screening for chemical-protein interactions, together with the network-based analysis of potential targets, will facilitate discovery and therapeutic applications of the Judea region plants. Such an approach could also be applied as an integrative platform for further searching the potential therapeutic targets of plants growing in other regions of the world.

  3. [Research on Depression in the GDR - Historical Lines of Development and Therapeutic Approaches].

    Science.gov (United States)

    Thormann, J; Himmerich, H; Steinberg, H

    2014-02-01

    Historical research has raised the issue of whether GDR psychiatry was isolated from Western influences to such an extent that an autonomous East German psychiatry developed. Taking a chronological approach and being based on a clearly defined range of topics, the objective of this paper is to identify specific contributions made by GDR psychiatry to academic research as well as the degree of its international orientation by focusing on the treatment and research on depression. We have performed a systematic review of the East German psychiatric journal "Psychiatrie, Neurologie und medizinische Psychologie" and a screening of all psychiatric textbooks that appeared in the GDR. Although East German psychiatry was oriented towards Soviet as well as Western developments, some internationally used therapeutic or conceptual innovations reached East German clinics only with some delay. Yet, East German psychiatrists have also contributed their own, independent nosological and therapeutic concepts to research on depression. Pivotal figures included, among others, R. Lemke (Jena), D. Müller-Hegemann (Leipzig) or K. Leonhard (Berlin). With regard to research on depression one cannot truly speak of an autonomous East German psychiatry. Developments in East and West were largely running in parallel. © Georg Thieme Verlag KG Stuttgart · New York.

  4. How noninvasive investigation has modified our therapeutic approach in vascular medicine

    Directory of Open Access Journals (Sweden)

    Antignani PL

    2013-03-01

    Full Text Available PL AntignaniItalian Society for Vascular InvestigationNoninvasive diagnostic methods have modified our therapeutic decision-making in several vascular diseases. In particular, many forms of surgical treatment, both endovascular and open, are performed based exclusively on evaluation with duplex scanning. The purpose of noninvasive ultrasound testing is to distinguish normal from pathological vessels, to classify a wide range of disease states, to assess the collateral circulation, and to do so in a safe and cost-effective manner. The primary aim is to identify patients who are at risk for acute and chronic vascular disease and who may require specific treatment. A secondary aim is to document progressive or recurrent disease in patients already known to be at risk. Of course, individual vascular laboratories must validate their own results against a suitable gold standard, and they have to guarantee the best quality and maximum accuracy.1     With regard to diseases of the carotid artery, color flow duplex scanning is the investigation of choice for diagnosis and measurement of carotid stenosis, provided that objective criteria are used and scanning is done by experienced operators. Several velocity criteria used to detect the presence and severity of carotid artery disease and the morphological evaluation of lesions allow us to have a specificity of 90% and a sensitivity of 99% when all categories of carotid disease are considered. On the basis of these criteria, we can identify the best therapeutic approach for specific pathological conditions.

  5. Exploring miRNA based approaches in cancer diagnostics and therapeutics.

    Science.gov (United States)

    Mishra, Shivangi; Yadav, Tanuja; Rani, Vibha

    2016-02-01

    MicroRNAs (miRNAs), a highly conserved class of tissue specific, small non-protein coding RNAs maintain cell homeostasis by negative gene regulation. Proper controlling of miRNA expression is required for a balanced physiological environment, as these small molecules influence almost every genetic pathway from cell cycle checkpoint, cell proliferation to apoptosis, with a wide range of target genes. Deregulation in miRNAs expression correlates with various cancers by acting as tumor suppressors and oncogenes. Although promising therapies exist to control tumor development and progression, there is a lack of efficient diagnostic and therapeutic approaches for delineating various types of cancer. The molecularly different tumors can be differentiated by specific miRNA profiling as their phenotypic signatures, which can hence be exploited to surmount the diagnostic and therapeutic challenges. Present review discusses the involvement of miRNAs in oncogenesis with the analysis of patented research available on miRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Generalised pustular psoriasis – a case report and review of therapeutic approaches

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    Agnieszka Osmola-Mańkowska

    2014-11-01

    Full Text Available Introduction. Generalised pustular psoriasis (GPP is regarded as a rare clinical subtype of psoriasis. The severity of GPP varies from a benign, chronic course to severe and widespread, life-threatening disease. Due to the uncommon nature of GPP, establishing treatment guidelines for this variant of psoriasis is challenging. Objective. To present the case of a patient with GPP with a short review of therapeutic approaches. Case report. Our patient was treated with standard methods such as acitretin, then cyclosporine and methotrexate as well as with biologic drug – infliximab. During the last and the most severe flare, combination therapy with systemic retinoid and PUVA (Re-PUVA was used. Conclusions. The treatment in GPP should be determined individually according to the severity of the disease, age, gender and comorbidities, as well as according to the physician’s experience with particular methods and their side effects. In addition, the availability of therapeutic options should be taken into consideration.

  7. New Therapeutic Approaches to Prevent or Delay Beta-Cell Failure in Diabetes

    Directory of Open Access Journals (Sweden)

    Ionica Floriana Elvira

    2015-09-01

    Full Text Available Background and aims: The most recent estimates of International Diabetes Federation indicate that 382 million people have diabetes, and the incidence of this disease is increasing. While in type 1 diabetes mellitus (T1DM beta-cell death is autoimmunemediated, type 2 diabetes mellitus (T2DM results from an interaction between genetic and environmental factors that impair beta-cell function and insulin action. Many people with T2DM remain unaware of their illness for a long time because symptoms may take years to appear or be recognized, while the body is affected by excess blood glucose. These patients are often diagnosed only when diabetes complications have already developed. The aim of this article was to perform a review based on literature data on therapeutic modalities to prevent/delay beta cell function decline. Material and Methods: We searched MEDLINE from 2000 to the present to identify the therapeutic approaches to prevent or delay beta-cell failure in patients with T2DM. Results and conclusions: Several common polymorphisms in genes linked to monogenic forms of diabetes appear to influence the response to T2DM pharmacotherapy. Recent studies report the role of the G protein coupled receptor 40 (GPR40, also known as Free Fatty Acids Receptor 1 (FFAR1 in the regulation of beta-cell function- CNX-011-67 (a GPR40 agonist has the potential to provide good and durable glycemic control in T2DM patients.

  8. Promising novel therapeutic approaches in the management of gastrointestinal stromal tumors.

    Science.gov (United States)

    Szucs, Zoltan; Thway, Khin; Fisher, Cyril; Bulusu, Ramesh; Constantinidou, Anastasia; Benson, Charlotte; van der Graaf, Winette Ta; Jones, Robin L

    2017-01-01

    Primary and secondary resistance to currently available licensed tyrosine kinase inhibitors poses a real clinical challenge in the management of advanced gastrointestinal stromal tumors. Within the frame of early phase clinical trials novel systemic treatments are currently being evaluated to target both the well explored and novel emerging downstream effectors of KIT and PDGFRA signaling. Alternative therapeutic approaches also include exploring novel inhibitors of the KIT/PDGFRA receptors, immune checkpoint and cyclin-dependent kinase inhibitors. The final clinical trial outcome data for these agents are highly anticipated. Integration of new diagnostic techniques into routine clinical practice can potentially guide tailored delivery of agents in the treatment of a highly polyclonal, heterogeneous disease such as heavily pretreated advanced gastrointestinal stromal tumor.

  9. Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

    Science.gov (United States)

    Rahman, Wahida; Dickenson, Anthony H

    2015-06-01

    Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics. Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy. Somatosensory phenotyping of chronic pain patients, as a surrogate of putative pain generating mechanisms, may predict patient response to treatment. Identification of new targets will inform and guide future research, aiding the development of more effective analgesics. Future clinical trial designs should implement sensory phenotyping of patients, as an inclusion or stratification criterion, in order to establish an individualized, mechanism-based treatment of osteoarthritis pain.

  10. An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

    Directory of Open Access Journals (Sweden)

    Syed Babar Jamal

    Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

  11. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

  12. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

  13. The third international meeting on genetic disorders in the RAS/MAPK pathway: towards a therapeutic approach.

    Science.gov (United States)

    Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D; Gripp, Karen W; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo; MacRae, Calum A; Messiaen, Ludwine; Mulero-Navarro, Sonia; Neel, Benjamin; Plotkin, Scott; Rauen, Katherine A; Roberts, Amy; Silva, Alcino J; Sittampalam, Sitta G; Zhang, Chao; Schoyer, Lisa

    2015-08-01

    "The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. © 2015 Wiley Periodicals, Inc.

  14. Systems Bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches.

    Science.gov (United States)

    Oulas, Anastasis; Minadakis, George; Zachariou, Margarita; Sokratous, Kleitos; Bourdakou, Marilena M; Spyrou, George M

    2017-11-27

    Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics. Systems Bioinformatics is the framework in which systems approaches are applied to such data, setting the level of resolution as well as the boundary of the system of interest and studying the emerging properties of the system as a whole rather than the sum of the properties derived from the system's individual components. A key approach in Systems Bioinformatics is the construction of multiple networks representing each level of the omics spectrum and their integration in a layered network that exchanges information within and between layers. Here, we provide evidence on how Systems Bioinformatics enhances computational therapeutics and diagnostics, hence paving the way to precision medicine. The aim of this review is to familiarize the reader with the emerging field of Systems Bioinformatics and to provide a comprehensive overview of its current state-of-the-art methods and technologies. Moreover, we provide examples of success stories and case studies that utilize such methods and tools to significantly advance research in the fields of systems biology and systems medicine. © The Author 2017. Published by Oxford University Press.

  15. [Therapeutic approaches to improve blood glucose control in a patient with type 2 diabetes on a metformin-sulfonylurea combination].

    Science.gov (United States)

    Scheen, A J; Paquot, N

    2011-04-01

    Beyond lifestyle changes, the management of type 2 diabetes comprises the administration of oral glucose-lowering agents, especially the classical metformin-sulfonylurea combination. If such a dual oral therapy could not (any more) obtain an adequate glucose control, intensified management becomes mandatory. Several therapeutic approaches may be proposed at this stage, with some advantages and disadvantages of each of them. The present clinical case aims at illustrating such difficult therapeutic choice. We will provide the pro-contra arguments concerning each therapeutic alternative and describe the practical modalities of an appropriate management according to the patient's characteristics.

  16. New therapeutic approaches for management of sport-induced muscle strains.

    Science.gov (United States)

    De Carli, Angelo; Volpi, Piero; Pelosini, Iva; Ferretti, Andrea; Melegati, Gianluca; Mossa, Luigi; Tornese, Davide; de Girolamo, Laura; Scarpignato, Carmelo

    2009-12-01

    Muscle strains are one of the most common sports-induced injuries. Depending on the severity and location of the muscle strain, different treatment approaches can be taken. This review highlights recent trends in conservative, pharmacologic, and surgical approaches to the management of sports-induced muscle injuries as presented at a symposium held during the 93rd Annual Congress of the Italian Society of Orthopedics and Traumatology (SIOT) in Rome, Italy in November 2008. Conservative approaches now include growth factor therapy and administration of autologous platelet-rich plasma during the early postinjury period; however, its use is currently considered a doping violation under the World Anti-Doping Agency code, therefore restricting its use to nonelite sports people only. Topical anti-inflammatory therapy is a promising therapeutic strategy, since it allows local analgesic and anti-inflammatory effects while minimizing systemic adverse events. As the drug delivery system is critical to clinical effectiveness, the advent of a new delivery system for ketoprofen via a new-generation plaster with a marked increase in tissue penetration and a clinical efficacy comparable with that of oral administration, provides a viable option in the treatment of single sport lesions. Surgical treatment of muscle lesions is less common than conservative and topical therapies and indications are limited to more serious injuries. Presentations from SIOT 2008 show that advances in our understanding of the healing process and in conservative, pharmacologic, and surgical treatment approaches to the management of sports-induced muscle strains contribute to better clinical outcomes, faster healing, and a swifter return to normal training and activity levels.

  17. Early hypopharyngeal cancer treated with different therapeutic approaches: a single-institution cohort analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nalee; Lee, Jeong Shin; Kim, Kyung Hwan; Park, Jong Eon; Lee, Chang Geol; Keum, Ki Chang [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    Early hypopharyngeal squamous cell carcinoma (HPSCC) is a rarely diagnosed disease, for which the optimal treatment has not been defined yet. We assessed patterns of failure and outcomes in early HPSCC treated with various therapeutic approaches to identify its optimal treatment. Thirty-six patients with stage I (n = 10) and II (n = 26) treated between January 1992 and March 2014 were reviewed. Patients received definitive radiotherapy (RT) (R group, n = 10), surgery only (S group, n = 19), or postoperative RT (PORT group, n = 7). All patients in both the R and PORT groups received elective bilateral neck irradiation. In the S group, 7 patients had ipsilateral and 8 had bilateral dissection, while 4 patients had no elective dissection. At a median follow-up of 48 months, the 5-year locoregional control (LRC) rate was 65%. Six patients had local failure, 1 regional failure (RF), 3 combined locoregional failures, and 2 distant failures. There was no difference in 5-year LRC among the R, S, and PORT groups (p = 0.17). The presence with a pyriform sinus apex extension was a prognosticator related to LRC (p = 0.01) in the multivariate analysis. Patients with a bilaterally treated neck showed a trend toward a lower RF rate (p = 0.08). This study shows that patients with early stage HPSCC involving the pyriform sinus apex might need a tailored approach to improve LRC. Additionally, our study confirms elective neck treatment might have an efficacious role in regional control.

  18. Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches.

    Science.gov (United States)

    Bonnet, Crystel; El-Amraoui, Aziz

    2012-02-01

    Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies. Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing. Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.

  19. The Roles of Carcinoembryonic Antigen in Liver Metastasis and Therapeutic Approaches

    Science.gov (United States)

    2017-01-01

    Metastasis is a highly complicated and sequential process in which primary cancer spreads to secondary organic sites. Liver is a well-known metastatic organ from colorectal cancer. Carcinoembryonic antigen (CEA) is expressed in most gastrointestinal, breast, and lung cancer cells. Overexpression of CEA is closely associated with liver metastasis, which is the main cause of death from colorectal cancer. CEA is widely used as a diagnostic and prognostic tumor marker in cancer patients. It affects many steps of liver metastasis from colorectal cancer cells. CEA inhibits circulating cancer cell death. CEA also binds to heterogeneous nuclear RNA binding protein M4 (hnRNP M4), a Kupffer cell receptor protein, and activates Kupffer cells to secrete various cytokines that change the microenvironments for the survival of colorectal cancer cells in the liver. CEA also activates cell adhesion-related molecules. The close correlation between CEA and cancer has spurred the exploration of many CEA-targeted approaches as anticancer therapeutics. Understanding the detailed functions and mechanisms of CEA in liver metastasis will provide great opportunities for the improvement of anticancer approaches against colorectal cancers. In this report, the roles of CEA in liver metastasis and CEA-targeting anticancer modalities are reviewed. PMID:28588612

  20. National Heart, Lung, and Blood Institute and the translation of cardiovascular discoveries into therapeutic approaches.

    Science.gov (United States)

    Galis, Zorina S; Black, Jodi B; Skarlatos, Sonia I

    2013-04-26

    The molecular causes of ≈4000 medical conditions have been described, yet only 5% have associated therapies. For decades, the average time for drug development through approval has taken 10 to 20 years. In recent years, the serious challenges that confront the private sector have made it difficult to capitalize on new opportunities presented by advances in genomics and cellular therapies. Current trends are disturbing. Pharmaceutical companies are reducing their investments in research, and biotechnology companies are struggling to obtain venture funds. To support early-stage translation of the discoveries in basic science, the National Institutes of Health and the National Heart, Lung, and Blood Institute have developed new approaches to facilitating the translation of basic discoveries into clinical applications and will continue to develop a variety of programs that create teams of academic investigators and industry partners. The goal of these programs is to maximize the public benefit of investment of taxpayer dollars in biomedical research and to lessen the risk required for industry partners to make substantial investments. This article highlights several examples of National Heart, Lung, and Blood Institute-initiated translational programs and National Institutes of Health translational resources designed to catalyze and enable the earliest stages of the biomedical product development process. The translation of latest discoveries into therapeutic approaches depends on continued federal funding to enhance the early stages of the product development process and to stimulate and catalyze partnerships between academia, industry, and other sources of capital.

  1. Chitosan and thiolated chitosan: Novel therapeutic approach for preventing corneal haze after chemical injuries.

    Science.gov (United States)

    Zahir-Jouzdani, Forouhe; Mahbod, Mirgholamreza; Soleimani, Masoud; Vakhshiteh, Faezeh; Arefian, Ehsan; Shahosseini, Saeed; Dinarvand, Rasoul; Atyabi, Fatemeh

    2018-01-01

    Corneal haze, commonly caused by deep physical and chemical injuries, can greatly impair vision. Growth factors facilitate fibroblast proliferation and differentiation, which leads to haze intensity. In this study, the potential effect of chitosan (CS) and thiolated-chitosan (TCS) nanoparticles and solutions on inhibition of fibroblast proliferation, fibroblast to myofibroblast differentiation, neovascularization, extracellular matrix (ECM) deposition, and pro-fibrotic cytokine expression was examined. Transforming growth factor beta-1 (TGFβ 1 ) was induced by interleukin-6 (IL6) in human corneal fibroblasts and expression levels of TGFβ 1 , Platelet-derived growth factor (PDGF), α-smooth muscle actins (α-SMA), collagen type I (Col I), fibronectin (Fn) and vascular endothelial growth factor (VEGF) were quantified using qRT-PCR. To assess wound-healing capacity, TCS-treated mice were examined for α-SMA positive cells, collagen deposition, inflammatory cells and neovascularization through pathological immunohistochemistry. The results revealed that CS and TCS could down-regulate the expression levels of TGFβ 1 and PDGF comparable to that of TGFβ 1 knockdown experiment. However, down-regulation of TGFβ 1 was not regulated through miR29b induction. Neovascularization along with α-SMA and ECM deposition were significantly diminished. According to these findings, CS and TCS can be considered as potential anti-fibrotic and anti-angiogenic therapeutics. Furthermore, TCS, thiolated derivative of CS, will increase mucoadhesion of the polymer at the corneal surface which makes the polymer efficient and non-toxic therapeutic approach for corneal injuries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept.

    Science.gov (United States)

    Peyrode, Caroline; Weber, Valérie; Voissière, Aurélien; Maisonial-Besset, Aurélie; Vidal, Aurélien; Auzeloux, Philippe; Gaumet, Vincent; Borel, Michèle; Dauplat, Marie-Mélanie; Quintana, Mercedes; Degoul, Françoise; Rédini, Françoise; Chezal, Jean-Michel; Miot-Noirault, Elisabeth

    2016-11-01

    To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosarcoma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [ 3 H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99m Tc-NTP 15-5 scintigraphic imaging of PGs, 1 H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the tolerability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma. Mol Cancer Ther; 15(11); 2575-85. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

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    Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

    2015-01-01

    This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

  4. Therapeutic approaches to genetic ion channelopathies and perspectives in drug discovery

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    Paola eImbrici

    2016-05-01

    Full Text Available In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets.

  5. [First SIBEN clinical consensus: diagnostic and therapeutic approach to patent ductus arteriosus in premature newborns].

    Science.gov (United States)

    Golombek, S G; Sola, A; Baquero, H; Borbonet, D; Cabañas, F; Fajardo, C; Goldsmit, G; Lemus, L; Miura, E; Pellicer, A; Pérez, J M; Rogido, M; Zambosco, G; van Overmeire, B

    2008-11-01

    To report the process and results of the first neonatal clinical consensus of the Ibero-American region. Two recognized experts in the field (Clyman and Van Overmeire) and 45 neonatologists from 23 countries were invited for active participation and collaboration. We developed 46 questions of clinical-physiological relevance in all aspects of patent ductus arteriosus (PDA). Guidelines for consensus process, literature search and future preparation of educational material and authorship were developed, reviewed and agreed by all. Participants from different countries were distributed in groups, and assigned to interact and work together to answer 3-5 questions, reviewing all global literature and local factors. Answers and summaries were received, collated and reviewed by 2 coordinators and the 2 experts. Participants and experts met in Granada, Spain for 4.5 h (lectures by experts, presentations by groups, discussion, all literature available). 31 neonatologists from 16 countries agreed to participate. Presentations by each group and general discussion were used to develop a consensus regarding: general management, availability of drugs (indomethacin vs. ibuprofen), costs, indications for echo/surgery, etc. Many steps were learnt by all present in a collaborative forum. This first consensus group of Ibero-American neonatologists SIBEN led to active and collaborative participation of neonatologists of 16 countries, improved education of all participants and ended with consensus development on clinical approaches to PDA. Furthermore, it provides recommendations for clinical care reached by consensus. Additionally, it will serve as a useful foundation for future SIBEN Consensus on other topics and it could become valuable as a model to decrease disparity in care and improve outcomes in this and other regions.

  6. The role of biological sciences in understanding the genesis and a new therapeutic approach to Alzheimer’s disease

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    Eugenia Tęgowska

    2011-01-01

    Full Text Available The paper contrasts the historical view on causal factors in Alzheimer’s disease (AD with the modern concept of the symptoms’ origin. Biological sciences dealing with cell structure and physiology enabled comprehension of the role of mitochondrial defects in the processes of formation of neurofibrillary tangles and β-amyloid, which in turn gives hope for developing a new, more effective therapeutic strategy for AD. It has been established that although mitochondria constantly generate free radicals, from which they are protected by their own defensive systems, in some situations these systems become deregulated, which leads to free radical-based mitochondrial defects. This causes an energetic deficit in neurons and a further increase in the free radical pool. As a result, due to compensation processes, formation of tangles and/or acceleration of β-amyloid production takes place. The nature of these processes is initially a protective one, due to their anti-oxidative action, but as the amount of the formations increases, their beneficial effect wanes. They become a storage place for substances enhancing free radical processes, which makes them toxic themselves. It is such an approach to the primary causal factor for AD which lies at the roots of the new view on AD therapy, suggesting the use of methylene blue-based drugs, laser or intranasally applied insulin. A necessary condition, however, for these methods’ effectiveness is definitely an earlier diagnosis of the disease. Although there are numerous diagnostic methods for AD, their low specificity and high price, often accompanied by a considerable level of patient discomfort, make them unsuitable for early, prodromal screening. In this matter a promising method may be provided using an olfactory test, which is an inexpensive and non-invasive method and thus suitable for screening, although as a test of low specificity, it should be combined with other methods. Introducing new methods

  7. Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room

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    Miguel Gus

    1999-03-01

    Full Text Available OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3% complained of high BP, and 61 (76.3% received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%. One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5% were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits. Currently, the therapeutic approach is not recommended, even in specialized clinics.

  8. Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2012-02-01

    Histone deacetylases (HDACs and RNA polymerase III (POLR3 play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A and an inhibitor of Polr3 (ML-60218 synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.

  9. Mining the Proteome of subsp. ATCC 25586 for Potential Therapeutics Discovery: An Approach

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    Abdul Musaweer Habib

    2016-12-01

    Full Text Available The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG Automated Annotation Server (KAAS resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

  10. The role of surgery in the therapeutic approach of gastric cancer liver metastases.

    Science.gov (United States)

    Mastoraki, Aikaterini; Benetou, Christina; Mastoraki, Sotiria; Papanikolaou, Ioannis S; Danias, Nikolaos; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

    2016-09-01

    Gastric cancer (GC) currently prevails as the second cause of death by malignancy worldwide. Estimations suggest that 35 % of affected patients appear with synchronous distant metastases. The vast majority of patients present with hepatic metastatic disease, sometimes accompanied by synchronous peritoneal and lung dissemination. The disease mostly remains asymptomatic at an early stage, with few reported cases of incidental abdominal discomfort. As the cancer advances, symptoms such as nausea or vomiting arise, along with indigestion and dysphagia, blood loss in the form of melena or hematemesis, as well as anorexia and weight loss. Having spread to the liver, it also causes jaundice due to hepatomegaly and general inanition. Despite recent research on the therapeutic strategies against GC metastatic disease, surgical resection appears the only potentially curative approach. Unfortunately, the majority of patients are not eligible to undergo surgical intervention. With regard to treatment modalities of the advanced stage disease, the role of metastasectomy is still debatable and quite unclear, while prolonged survival was succeeded only under certain specific circumstances. Systemic chemotherapy remains however another option, as well as local management in the form of cryotherapy, radiofrequency ablation, or transcatheter arterial chemoembolization. The aims of this review were to evaluate the results of surgical treatment for metastatic GC with special reference to the extent of its histological spread and to present the recent literature in order to provide an update on the current concepts of advanced surgical management of this entity. Relevant publications in the last two decades are briefly reviewed.

  11. Dapoxetine: An Innovative Approach in the Therapeutic Management In Animal Model of Depression

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    Hira Rafi

    2016-01-01

    Full Text Available Stress is a complicated condition that effects on person’s mental and physical health, and it is the precursor of other psychological disorders mainly depression. Serotonin (5-Hydroxytryptamine; 5-HT is well known to have hypofunction in unpredictable chronic mild stress whereas, unpredictable chronic mild stress (UCMS has produced the most steady and continuous results of anhedonia and learned helplessness particularly in rats. The stress-induced depressive like behavior can be reversed by many antidepressants such as SSRIs. Selective serotonin [5-hydroxytryptamine (5-HT] reuptake inhibitors (SSRIs is mostly prescribed antidepressant that can deplete neurochemical and behavioral deficits. The present study was designed to investigate whether repeated administration of dapoxetine at dose (1.0 mg/kg could reverse the behavioral deficits induced by UCMS in rat model of depression. UCMS induced behavioral deficits. Locomotor  activity in familiar environment (home cage, novel (open field environment and anxiolytic behavior in light/dark activity box were greater in unstressed group than stressed group. The inhibition of serotonin reuptake at pre-synaptic receptors by repeated dapoxetine administration is mainly the mechanism involved and discussed. This particular study may assist in novel approach for understanding the interaction between stress and behavioral functions and extending the therapeutic use of dapoxetine.

  12. Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach.

    Science.gov (United States)

    Korsten, Peter; Strohmayer, Katharina; Baughman, Robert P; Sweiss, Nadera J

    2016-03-01

    Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach.

  13. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation.

    Science.gov (United States)

    Langdon, Amy; Crook, Nathan; Dantas, Gautam

    2016-04-13

    The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food. Therefore, it is now more important than ever to revisit how we use antibiotics. This review summarizes current research on the short-term and long-term consequences of antibiotic use on the human microbiome, from early life to adulthood, and its effect on diseases such as malnutrition, obesity, diabetes, and Clostridium difficile infection. Motivated by the consequences of inappropriate antibiotic use, we explore recent progress in the development of antivirulence approaches for resisting infection while minimizing resistance to therapy. We close the article by discussing probiotics and fecal microbiota transplants, which promise to restore the microbiota after damage of the microbiome. Together, the results of studies in this field emphasize the importance of developing a mechanistic understanding of gut ecology to enable the development of new therapeutic strategies and to rationally limit the use of antibiotic compounds.

  14. Insomnia in childhood and adolescence: clinical aspects, diagnosis, and therapeutic approach.

    Science.gov (United States)

    Nunes, Magda Lahorgue; Bruni, Oliviero

    2015-01-01

    To review the clinical characteristics, comorbidities, and management of insomnia in childhood and adolescence. This was a non-systematic literature review carried out in the PubMed database, from where articles published in the last five years were selected, using the key word "insomnia" and the pediatric age group filter. Additionally, the study also included articles and classic textbooks of the literature on the subject. During childhood, there is a predominance of behavioral insomnia as a form of sleep-onset association disorder (SOAD) and/or limit-setting sleep disorder. Adolescent insomnia is more associated with sleep hygiene problems and delayed sleep phase. Psychiatric (anxiety, depression) or neurodevelopmental disorders (attention deficit disorder, autism, epilepsy) frequently occur in association with or as a comorbidity of insomnia. Insomnia complaints in children and adolescents should be taken into account and appropriately investigated by the pediatrician, considering the association with several comorbidities, which must also be diagnosed. The main causes of insomnia and triggering factors vary according to age and development level. The therapeutic approach must include sleep hygiene and behavioral techniques and, in individual cases, pharmacological treatment. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  15. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    Science.gov (United States)

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  16. Mechanisms of atherosclerosis and cardiovascular disease in antiphospholipid syndrome and systemic lupus erythematosus. New therapeutic approaches.

    Science.gov (United States)

    Lopez-Pedrera, Chary; Aguirre-Zamorano, M Ángeles; Pérez-Sánchez, Carlos

    2017-08-22

    Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are 2 highly related autoimmune-rheumatic diseases associated with an increased risk of developing cardiovascular (CV) diseases. Despite the great progresses made in understanding the pathological mechanisms leading to CV diseases in those pathologies, there is still the unmet need to improve long term prognosis. CV diseases in SLE and APS is thought to happen as the result of a complex interaction between traditional CV risk factors, immune deregulation and disease activity, including the synergic effect of cytokines, chemokines, adipokines, proteases, autoantibodies, adhesion receptors, oxidative stress and a plethora of intracellular signalling molecules. Genomic and epigenomic analyses have further allowed the identification of specific signatures explaining the proathero-thrombotic profiles of APS and SLE patients. This review examines the complex role of these heterogeneous factors, and analyses new therapeutic approaches under study to reduce the CV risk in these autoimmune disorders. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  17. Xeroderma pigmentosum: diagnostic procedures, interdisciplinary patient care, and novel therapeutic approaches.

    Science.gov (United States)

    Lehmann, Janin; Schubert, Steffen; Emmert, Steffen

    2014-10-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disease, caused by a gene defect in the nucleotide-excision-repair (NER) pathway or in translesional DNA synthesis. At the age of eight, patients already develop their first skin cancers due to this DNA repair defect. In contrast, in the Caucasian population the first tumor formation in UV exposed skin regions occurs at a mean age of 60. The clinical picture among patients suffering from XP is highly diverse and includes signs of accelerated skin aging, and UV-induced skin cancers, as well as ophthalmologic and neurological symptoms. Patients should therefore receive interdisciplinary care. This includes dermatologists, ophthalmologists, ENT specialists, neurologists, and human geneticists. Patients with XP are clinically diagnosed, but this may be supported by molecular-genetic and functional analyses. These analyses allow pinpointing the exact disease-causing gene defect (complementation group assignment, detection of the type and location of the mutation within the gene). The resulting information is already relevant to predict the course of disease and symptoms and probably will be utilized for individualized therapeutic approaches in the future. Recently, enhanced repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons by certain antibiotics could be demonstrated. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  18. A multidisciplinary approach to therapeutic risk management of the suicidal patient

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    Grant CL

    2015-06-01

    Full Text Available Cynthia L Grant,1,2 Jaimie L Lusk3 1Arapahoe/Douglas Mental Health Network, Englewood, CO, 2School of Education and Human Development, University of Colorado Denver, Denver, CO, 3Mental Health Service, VA Portland Health Care System, Portland, OR, USA Abstract: As health care trends toward a system of care approach, providers from various disciplines strive to collaborate to provide optimal care for their patients. While a multidisciplinary approach to suicide risk assessment and management has been identified as important for reducing suicidality, standardized clinical guidelines for such an approach do not yet exist. In this article, the authors propose the adoption of the therapeutic risk management of the suicidal patient (TRMSP to improve suicide risk assessment and management within multidisciplinary systems of care. The TRMSP, which has been fully articulated in previous articles, involves augmenting clinical risk assessment with structured instruments, stratifying risk in terms of both severity and temporality, and developing and documenting a safety plan. Augmenting clinical risk assessments with reliable and valid structured instruments serves several functions, including ensuring important aspects of suicide are addressed, establishing a baseline for suicidal thoughts and behaviors, facilitating interprofessional communication, and mitigating risk. Similarly, a two-dimensional risk stratification qualifying suicide risk in terms of both severity and temporality can enhance communication across providers and settings and improve understanding of acute crises in the context of chronic risk. Finally, safety planning interventions allow providers and patients to collaboratively create a personally meaningful plan for managing a suicidal crisis that can be continually modified across time with multiple providers in different care settings. In a busy care environment, the TRMSP can provide concrete guidance on conducting clinically and

  19. Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure.

    Science.gov (United States)

    George, Jeffy; Mattapallil, Joseph J

    2018-01-01

    Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus. Interferon-α (IFN-α) is an innate cytokine that has been shown to activate intracellular defenses capable of restricting and controlling HIV. IFN-α, however, harbors numerous functional subtypes that have been reported to display different binding affinities and potency. Recent studies have suggested that certain subtypes such as IFN-α8 and IFN-α14 have potent anti-HIV activity with little or no immune activation, whereas other subtypes such as IFN-α4, IFN-α5, and IFN-α14 activate NK cells. Could these subtypes be used in combination with other strategies to reduce the latent viral reservoir? Here, we review the role of IFN-α subtypes in HIV infection and discuss the possibility that certain subtypes could be potential adjuncts to a "shock and kill" or therapeutic vaccination strategy leading to better control of the latent reservoir and subsequent functional cure.

  20. Phosphodiesterase-4 inhibition as a therapeutic approach to treat capillary leakage in systemic inflammation.

    Science.gov (United States)

    Schick, Martin Alexander; Wunder, Christian; Wollborn, Jakob; Roewer, Norbert; Waschke, Jens; Germer, Christoph-Thomas; Schlegel, Nicolas

    2012-06-01

    In sepsis and systemic inflammation, increased microvascular permeability and consecutive breakdown of microcirculatory flow significantly contribute to organ failure and death. Evidence points to a critical role of cAMP levels in endothelial cells to maintain capillary endothelial barrier properties in acute inflammation. However, approaches to verify this observation in systemic models are rare. Therefore we tested here whether systemic application of the phosphodiesterase-4-inhibitors (PD-4-Is) rolipram or roflumilast to increase endothelial cAMP was effective to attenuate capillary leakage and breakdown of microcirculatory flow in severe lipopolysaccharide (LPS)-induced systemic inflammation in rats. Measurements of cAMP in mesenteric microvessels demonstrated significant LPS-induced loss of cAMP levels which was blocked by application of rolipram. Increased endothelial cAMP by application of either PD-4-I rolipram or roflumilast led to stabilization of endothelial barrier properties as revealed by measurements of extravasated FITC-albumin in postcapillary mesenteric venules. Accordingly, microcirculatory flow in mesenteric venules was significantly increased following PD-4-I treatment and blood gas analyses indicated improved metabolism. Furthermore application of PD-4-I after manifestation of LPS-induced systemic inflammation and capillary leakage therapeutically stabilized endothelial barrier properties as revealed by significantly reduced volume resuscitation for haemodynamic stabilization. Accordingly microcirculation was significantly improved following treatment with PD-4-Is. Our results demonstrate that inflammation-derived loss of endothelial cAMP contributes to capillary leakage which was blocked by systemic PD-4-I treatment. Therefore these data suggest a highly clinically relevant and applicable approach to stabilize capillary leakage in sepsis and systemic inflammation.

  1. Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach.

    Science.gov (United States)

    Srinivasan, Venkataramanujam; Ahmad, Asma H; Mohamed, Mahaneem; Zakaria, Rahimah

    2012-05-01

    Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin

  2. A forgotten approach after cardiac arrest due to acute myocardial ınfarction: Neuroprotective therapeutic hypothermia

    Directory of Open Access Journals (Sweden)

    Abdullah Özçelik

    2018-02-01

    Full Text Available In patients with spontaneous circulation after cardiopulmonary resuscitation, therapeutic hypothermia is defined as the reduction of body temperature to 32-34 ° C within the first 4-6 hours for neuroprotective purposes and to be maintained at this level for 12-24 hours after reaching the target temperature. Therapeutic hypothermia has been practiced since the 1940s. The aim of therapeutic hypothermia is to reduce cerebral edema, convulsive activity, metabolic demand and associated complications by providing low body heat. Therapeutic hypothermia is applied to increase life expectancy and quality of life. In out-of-hospital cardiac arrest, should be performed in comatose patients where initial rhythm is ventricular fibrillation and spontaneous circulation is returned. Herein, we present a 44 years old patient who had an aborted sudden cardiac death due to acute myocardial infarction and performing cardiopulmonary resuscitation for 30 minutes and discharged after 6 days with a successful therapeutic hypothermia.

  3. The diagnostic and therapeutic approach of a primary bilateral leiomyoma of the ovaries: a case report and a literature review.

    NARCIS (Netherlands)

    Esch, E.M. van; Wijngaarden, S.E. van; Schaafsma, H.E.; Smeets, M.J.; Rhemrev, J.P.

    2011-01-01

    INTRODUCTION: A primary fibroid (leiomyoma) arising from both ovaries is rare and can be difficult to diagnose as a result of the low incidence and its indistinctive presentation. A literature review on the diagnostic and therapeutic approach of this rare benign tumour is presented. We describe a

  4. Semantic Document Image Classification Based on Valuable Text Pattern

    Directory of Open Access Journals (Sweden)

    Hossein Pourghassem

    2011-01-01

    Full Text Available Knowledge extraction from detected document image is a complex problem in the field of information technology. This problem becomes more intricate when we know, a negligible percentage of the detected document images are valuable. In this paper, a segmentation-based classification algorithm is used to analysis the document image. In this algorithm, using a two-stage segmentation approach, regions of the image are detected, and then classified to document and non-document (pure region regions in the hierarchical classification. In this paper, a novel valuable definition is proposed to classify document image in to valuable or invaluable categories. The proposed algorithm is evaluated on a database consisting of the document and non-document image that provide from Internet. Experimental results show the efficiency of the proposed algorithm in the semantic document image classification. The proposed algorithm provides accuracy rate of 98.8% for valuable and invaluable document image classification problem.

  5. Contact refusal by children following acrimonious separation: therapeutic approaches with children and parents.

    Science.gov (United States)

    Dejong, Margaret; Davies, Hilary

    2013-04-01

    This paper aims to build on the existing literature, by presenting some thoughts based on clinical experience with nine families of children referred for intractable contact refusal with one parent following marital separation. This particular group of high-conflict divorce cases engenders an inordinate amount of frustration both within the courts and therapeutic agencies. We outline here our assessment process and therapeutic strategies, as well as consideration of the role of the wider professional system and the courts. We conclude that whether or not direct contact with the rejected parent is achieved, useful therapeutic work can be carried out to assist children in moving on with their lives.

  6. Evaluating statistical approaches to leverage large clinical datasets for uncovering therapeutic and adverse medication effects.

    Science.gov (United States)

    Choi, Leena; Carroll, Robert J; Beck, Cole; Mosley, Jonathan D; Roden, Dan M; Denny, Joshua C; Van Driest, Sara L

    2018-04-18

    Phenome-wide association studies (PheWAS) have been used to discover many genotype-phenotype relationships and have the potential to identify therapeutic and adverse drug outcomes using longitudinal data within electronic health records (EHRs). However, the statistical methods for PheWAS applied to longitudinal EHR medication data have not been established. In this study, we developed methods to address two challenges faced with reuse of EHR for this purpose: confounding by indication, and low exposure and event rates. We used Monte Carlo simulation to assess propensity score (PS) methods, focusing on two of the most commonly used methods, PS matching and PS adjustment, to address confounding by indication. We also compared two logistic regression approaches (the default of Wald vs. Firth's penalized maximum likelihood, PML) to address complete separation due to sparse data with low exposure and event rates. PS adjustment resulted in greater power than propensity score matching, while controlling Type I error at 0.05. The PML method provided reasonable p-values, even in cases with complete separation, with well controlled Type I error rates. Using PS adjustment and the PML method, we identify novel latent drug effects in pediatric patients exposed to two common antibiotic drugs, ampicillin and gentamicin. R packages PheWAS and EHR are available at https://github.com/PheWAS/PheWAS and at CRAN (https://www.r-project.org/), respectively. The R script for data processing and the main analysis is available at https://github.com/choileena/EHR. leena.choi@vanderbilt.edu. Supplementary data are available at Bioinformatics online.

  7. Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.

    Science.gov (United States)

    Clossen, Bryan L; Reddy, Doodipala Samba

    2017-06-01

    This article describes the recent advances in epileptogenesis and novel therapeutic approaches for the prevention of epilepsy, with a special emphasis on the pharmacological basis of disease-modification of epileptogenesis for curing epilepsy. Here we assess animal studies and human clinical trials of epilepsy spanning 1982-2016. Epilepsy arises from a number of neuronal factors that trigger epileptogenesis, which is the process by which a brain shifts from a normal physiologic state to an epileptic condition. The events precipitating these changes can be of diverse origin, including traumatic brain injury, cerebrovascular damage, infections, chemical neurotoxicity, and emergency seizure conditions such as status epilepticus. Expectedly, the molecular and system mechanisms responsible for epileptogenesis are not well defined or understood. To date, there is no approved therapy for the prevention of epilepsy. Epigenetic dysregulation, neuroinflammation, and neurodegeneration appear to trigger epileptogenesis. Targeted drugs are being identified that can truly prevent the development of epilepsy in at-risk people. The promising agents include rapamycin, COX-2 inhibitors, TRK inhibitors, epigenetic modulators, JAK-STAT inhibitors, and neurosteroids. Recent evidence suggests that neurosteroids may play a role in modulating epileptogenesis. A number of promising drugs are under investigation for the prevention or modification of epileptogenesis to halt the development of epilepsy. Some drugs in development appear rational for preventing epilepsy because they target the initial trigger or related signaling pathways as the brain becomes progressively more prone to seizures. Additional research into the target validity and clinical investigation is essential to make new frontiers in curing epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. [Psychopathology and film: a valuable interaction?].

    Science.gov (United States)

    van Duppen, Z; Summa, M; Fuchs, T

    2015-01-01

    Film or film fragments are often used in psychopathology education. However, so far there have been very few articles that have discussed the benefits and limitations of using films to explain or illustrate psychopathology. Although numerous films involves psychopathology in varying degrees, it is not clear how we can use films for psychopathology education. To examine the advantages, limitations and possible methods of using film as a means of increasing our knowledge and understanding of psychiatric illnesses. We discuss five examples that illustrate the interaction of film and psychopathology. On the one hand we explain how the psychopathological concepts are used in each film and on the other hand we explain which aspects of each film are valuable aids for teaching psychopathology. The use of film makes it possible to introduce the following topics in psychopathological teaching programme: holistic psychiatric reasoning, phenomenology and the subjective experience, the recognition of psychopathological prototypes and the importance of context. There is undoubtedly an analogy between the method we have chosen for teaching psychopathology with the help of films and the holistic approach of the psychiatrist and his or her team. We believe psychopathology education can benefit from films and we would recommend our colleagues to use it in this way.

  9. An Approach to Optimise Therapeutic Vancomycin Dosage in a Haemodialysis Population

    LENUS (Irish Health Repository)

    Gunning, H

    2016-10-01

    Haemodialysis patients are at risk of gram-positive bacteraemia and commonly require intravenous vancomycin. Intravenously administered vancomycin is primarily excreted by the kidney and exhibits complex pharmacokinetics in haemodialysis patients; achieving therapeutic levels can be challenging. An audit in our unit showed current practises of vancomycin administration resulted in a high proportion of sub-therapeutic levels. A new protocol was developed with fixed weight-based loading and subsequent dosing guided by pre-dialysis levels, target levels were 10-20mg\\/L. Its effectiveness was prospectively evaluated between 24th September 2012, and 8th February 2013. During this period 25 patients commenced vancomycin, 15 were included. In total, 112 vancomycin levels were taken, 94 (84%) were therapeutic, this was a significant improvement compared to previous practise (odds ratio 5.4, CI 3.1-9.4, p < 0.0001). In conclusion, our study shows this protocol can consistently and reliably achieve therapeutic vancomycin levels

  10. Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment

    Czech Academy of Sciences Publication Activity Database

    Zarone, M.R.; Misso, G.; Grimaldi, A.; Zappavigna, S.; Russo, M.; Amler, Evžen; Di Martino, M.T.; Amodio, N.; Tagliaferri, P.; Tassone, P.; Caraglia, M.

    2017-01-01

    Roč. 7, dec (2017), s. 17949 ISSN 2045-2322 Institutional support: RVO:68378041 Keywords : gamma-secretase inhibitors * tumor-suppressor network * breast - cancer Subject RIV: FP - Other Medical Disciplines OBOR OECD: Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions (pharmacogenomics, gene-based therapeutics) Impact factor: 4.259, year: 2016

  11. Development of new therapeutic methods of lung cancer through team approach study

    International Nuclear Information System (INIS)

    Park, Jong Ho; Zo, Jae Ill; Baek, Hee Jong; Jung, Jin Haeng; Lee, Jae Cheol; Ryoo, Baek Yeol; Kim, Mi Sook; Choi, Du Hwan; Park, Sun Young; Lee, Hae Young

    2000-12-01

    The aims of this study were to make the lung cancer clinics in Korea Cancer Center Hospital, and to establish new therapeutic methods of lung cancer for increasing the cure rate and survival rate of patients. Also another purpose of this study was to establish a common treatment method in our hospital. All patients who were operated in Korea Cancer Center Hospital from 1987 due to lung cancer were followed up and evaluated. And we have been studied the effect of postoperative adjuvant therapy in stage I, II, IIIA non-small cell lung cancer patients from 1989 with the phase three study form. Follow-up examinations were scheduled in these patients and interim analysis was made. Also we have been studied the effect of chemo-therapeutic agents in small cell lung cancer patients from 1997 with the phase two study form. We evaluated the results of this study. Some important results of this study were as follows. 1. The new therapeutic method (surgery + MVP chemotherapy) was superior to the standard therapeutic one in stage I Non-small cell lung cancer patients. So, we have to change the standard method of treatment in stage I NSCLC. 2. Also, this new therapeutic method made a good result in stage II NSCLC patients. And this result was reported in The Annals of Thoracic Surgery. 3. However, this new therapeutic method was not superior to the standard treatment method (surgery only) in stage IIIA NSCLC patients. So, we must develop new chemo-therapeutic agents in the future for advanced NSCLC patients. 4. In the results of the randomized phase II studies about small cell lung cancer, there was no difference in survival between Etoposide + Carboplatin + Ifosfamide + Cisplatin group and Etoposide + Carboplatin + Ifosfamide + Cisplatin + Tamoxifen group in both the limited and extended types of small cell lung cancer patients

  12. Gene editing in hematopoietic stem cells: a potential therapeutic approach for Fanconi anemia

    International Nuclear Information System (INIS)

    Diez Cabezas, B.

    2015-01-01

    targeting efficiency, due to the toxicity associated with the nucleofection of cells treated with these nanoparticles. In our next step, we moved from healthy donor HSCs to FA hematopoietic cells. Using a therapeutic donor vector carrying the FANCA gene, we demonstrated that gene targeting can correct the phenotype in a FA-A LCL. This was deduced from the restoration of FANCD2 foci formation and the reversion of the sensitivity of FA-A cells to interstrand cross linkers, such as mitomycin C (MMC). To improve the gene targeting efficiency in FA-A hematopoietic cells, we also investigated the effects mediated by the transient inhibition of anti-recombinase PARI. Although the inhibition of PARI increased RAD51 foci, no significant increase of homology directed repair efficiency was observed. In a final set of experiments we demonstrated that our gene targeting approach has also taken place in hematopoietic progenitor cells from FA-A patients, leading to a partial reversion in their hyper-sensitivity to MMC. Our study demonstrates for the first time that gene targeting in the AAVS1 safe harbor locus is feasible in hematopoietic cells from Fanconi anemia-A patients, opening up new perspectives for the future gene therapy of this and other monogenic diseases of the hematopoietic system.(Author)

  13. Gene editing in hematopoietic stem cells: a potential therapeutic approach for Fanconi anemia

    Energy Technology Data Exchange (ETDEWEB)

    Diez Cabezas, B.

    2015-07-01

    targeting efficiency, due to the toxicity associated with the nucleofection of cells treated with these nanoparticles. In our next step, we moved from healthy donor HSCs to FA hematopoietic cells. Using a therapeutic donor vector carrying the FANCA gene, we demonstrated that gene targeting can correct the phenotype in a FA-A LCL. This was deduced from the restoration of FANCD2 foci formation and the reversion of the sensitivity of FA-A cells to interstrand cross linkers, such as mitomycin C (MMC). To improve the gene targeting efficiency in FA-A hematopoietic cells, we also investigated the effects mediated by the transient inhibition of anti-recombinase PARI. Although the inhibition of PARI increased RAD51 foci, no significant increase of homology directed repair efficiency was observed. In a final set of experiments we demonstrated that our gene targeting approach has also taken place in hematopoietic progenitor cells from FA-A patients, leading to a partial reversion in their hyper-sensitivity to MMC. Our study demonstrates for the first time that gene targeting in the AAVS1 safe harbor locus is feasible in hematopoietic cells from Fanconi anemia-A patients, opening up new perspectives for the future gene therapy of this and other monogenic diseases of the hematopoietic system.(Author)

  14. Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach

    Directory of Open Access Journals (Sweden)

    Sunee Lertsinudom

    2014-12-01

    Full Text Available Epilepsy is a common public health problem and needs multi-disciplinary treatment. Therapeutic drug monitoring (TDM is one of step of the multi-disciplinary treatment in epilepsy at Epilepsy clinic, Khon Kaen University (Thailand. The TDM service has been established since 2008. Here, we aimed to study the roles of TDM order and epilepsy control. This is a prospective descriptive study in which data collection was done from January 1 to December 31, 2010, the period when pharmacists took part in assessing the appropriateness in measurement and interpretation of TDM in order to provide suggestions for physicians. The 112 patients under study had an average age of 38.21±15.36 years; 254 samples were collected for therapeutic drug monitoring; phenytoin was submitted mostly for drug monitoring at 46.46%; 44.49% of sub-missions for drug level monitoring were made owing to a suspected sub-therapeutic level. Associations were found between reasons of sending samples for drug level monitoring and the measured drug levels, i.e., 66.67% of drug levels found was so low that they were undetectable in sample for patients’ compliance investigation and 38.94% of the drug levels were found to be sub-therapeutic as for the case where submission of samples was done because of suspected sub-therapeutic level, 40% of the cases were found to be in toxicity range in the cases with suspected over-therapeutic levels and monitoring levels, 58.25% were found to be within the therapeutic range. Pharmacists used the interpreted results in patients’ care by recommending physicians to monitor therapeutic drug closely, to adjust the dosage of drugs, and to recommend checking patients’ compliance in their use of drugs at 56.5, 38.9, and 4.3%, respectively. Physicians’ responses were found to be absolute follow, partial follow and not follow at 77.95, 11.03, and 7.48%, respectively. In conclusion, associations were found between reasons of TDM order and measured drug

  15. Maternally Sequestered Therapeutic Polypeptides – A New Approach for the Management of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Eric eGeorge

    2014-09-01

    Full Text Available The last several decades have seen intensive research into the molecular mechanisms underlying the symptoms of preeclampsia. While the underlying cause of preeclampsia is believed to be defective placental development and resulting placental ischemia, it is only recently that the links between the ischemic placenta and maternal symptomatic manifestation have been elucidated. Several different pathways have been implicated in the development of the disorder; most notably production of the anti-angiogenic protein sFlt-1, induction of auto-immunity and inflammation, and production of reactive oxygen species. While the molecular mechanisms are becoming clearer, translating that knowledge into effective therapeutics has proven elusive. Here we describe a number of peptide based therapies we have developed to target theses pathways, and which are currently being tested in preclinical models. These therapeutics are based on a synthetic polymeric carrier elastin-like polypeptide (ELP, which can be synthesized in various sequences and sizes to stabilize the therapeutic peptide and avoid crossing the placental interface. This prevents fetal exposure and potential developmental effects. The therapeutics designed will target known pathogenic pathways, and the ELP carrier could prove to be a versatile delivery system for administration of a variety of therapeutics during pregnancy.

  16. The teaching–learning of Therapeutic Physical Culture from a didactic approach

    Directory of Open Access Journals (Sweden)

    Manuel Alejandro Romero-León

    2017-07-01

    Full Text Available The theoretical analysis of the main references of the Therapeutic Physical Culture, from a didactic perspective, allows to recognize the marked therapeutic intentionality that has prevailed in the teaching-learning of the TPC, to the detriment of the formation for the life and the solution of the problems Which are presented with the disease by the students, independently. Therefore, it is important to promote from the didactics to the teaching of this subject. In order to do so, three fundamental components were elaborated: cultural-procedural, instrumental-executor and an interactive component of personal involvement from which the objectives, contents and methods of the teaching of Therapeutic Physical Culture were strengthened. In this way a process is conceived that enables an active cognitive activity and the formation of abilities for the interaction with the different ailments.

  17. Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.

    Science.gov (United States)

    Del Nogal-Avila, Maria; Donoro-Blazquez, Hector; Saha, Manish K; Marshall, Caroline B; Clement, Lionel C; Macé, Camille E A; Chugh, Sumant S

    2016-07-01

    Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease. Copyright © 2016 the American Physiological Society.

  18. Usefulness of CT-scan in the diagnosis and therapeutic approach of gallstone ileus: report of two surgically treated cases

    OpenAIRE

    Michele, Danzi; Luciano, Grimaldi; Massimiliano, Fabozzi; Stefano, Reggio; Roberta, Danzi; Ernesto, Soscia; Bruno, Amato

    2013-01-01

    Background Gallstone ileus is a rare cause of gastrointestinal obstruction, more frequent in elderly patients, whose treatment is essentially surgical, although some para-surgical and mini-invasive possibilities exist, allowing the solution of such obstructive condition in a completely non-invasive way. Description In our study, after reporting two cases of biliary ileus managed by our surgical division, we will analyze the most suitable diagnostic procedures and the therapeutic approaches to...

  19. Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression

    OpenAIRE

    Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

    2016-01-01

    Background To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Methods Retrospective multicenter study using the Swiss ...

  20. The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Toward a Therapeutic Approach

    OpenAIRE

    Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D.; Gripp, Karen W.; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo

    2015-01-01

    "The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regard...

  1. Disruption of the Interaction of the Androgen Receptor with Chromatin: A Novel Therapeutic Approach in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0543 TITLE: Disruption of the Interaction of the Androgen Receptor with Chromatin : A Novel Therapeutic Approach in...DATES COVERED 8 Sep 2015 - 7 Sep 2016 4. TITLE AND SUBTITLE Disruption of the Interaction of the Androgen Receptor with Chromatin : A Novel 5a. CONTRACT...1: Select and evaluate peptides/peptidomimetics in models of PCa. Aim 2: Determine the molecular action of peptide /peptidomimetics at the chromatin

  2. The therapeutic short story as a way from resilience. A first approach.

    Directory of Open Access Journals (Sweden)

    Mónica Bruder

    2015-09-01

    Full Text Available Starting from the “therapeutic short story” tool, we wonder its possible relationship with the concept of “resiliencia” and the level of influence. Theory is complemented by an experimental study and a model case of example. 

  3. Therapeutic landscapes and postcolonial theory: a theoretical approach to medical tourism.

    Science.gov (United States)

    Buzinde, Christine N; Yarnal, Careen

    2012-03-01

    This paper draws on two conceptual frameworks, therapeutic landscapes and postcolonial theory, to discuss aspects of medical tourism not addressed in extant literature. Building on the intersection between postcolonial and therapeutic landscapes scholarship, it highlights inequalities related to the production of national therapeutic landscapes located in postcolonial regions as well as their discursive (re)positioning as medical tourism destinations. As a framework, therapeutic landscapes can facilitate an understanding of medical tourism sites as curative spaces which combine modern and alternative forms of medicine with travel and leisure. Postcolonial theory critiques the economic, moral and cultural tensions emerging from the intersection between corporations that provide cheaper and more attractive medical services, and the nations on the periphery struggling to offer high medical standards that may not be accessible to their own local populations. In an effort to enhance scholarship on medical tourism, these conceptual frameworks are offered as points of departure, rather than sites of arrival, through which critical dialog on medical tourism can be sustained and broadened. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Computer-Aided Drug Design Approaches to Study Key Therapeutic Targets in Alzheimer’s Disease

    NARCIS (Netherlands)

    Lemos, A.; Melo, Rita; de Sousa Moreira, I.; Cordeiro, Maria Natália D S

    2017-01-01

    Alzheimer’s Disease (AD) is one of the most common and complex age-related neurodegenerative disorders in elderly people. Currently there is no cure for AD, and available therapeutic alternatives only improve both cognitive and behavioral functions. For that reason, the search for anti-AD

  5. Integrative Therapeutic Approaches for the Management and Control of Nausea in Children Undergoing Cancer Treatment: A Systematic Review of Literature.

    Science.gov (United States)

    Momani, Tha'er G; Berry, Donna L

    Chemotherapy-induced nausea and vomiting (CINV) continues to be a common symptom experienced by children undergoing cancer treatment despite the use of contemporary antiemetics. Integrative therapeutic approaches in addition to standard pharmacologic antiemetic regimes offer potential to control CINV. The purpose of this review was to identify current evidence on integrative therapeutic approaches for the control of CINV in children with cancer. Online search engines (PubMed, CINAHL, PsychINFO) were queried using MESH terms. Titles, abstracts, and then full-text articles were reviewed for relevance to the review. The search resulted in 53 studies. Twenty-one studies met our review criteria. Integrative therapies identified included acupuncture/acupressure, aromatherapy, herbal supplements, hypnosis, and other cognitive behavioral interventions. Our review identified little information on the effectiveness and safety of most integrative therapeutic approaches for the control and management of CINV in children with cancer. However, evidence from adult cancer studies and some pediatric studies identify promising interventions for further testing.

  6. Multimodal therapeutic approach of vaginismus: an innovative approach through trigger point infiltration and pulsed radiofrequency of the pudendal nerve

    Directory of Open Access Journals (Sweden)

    Joana Chaves Gonçalves Rodrigues de Carvalho

    Full Text Available Abstract Vaginismus is a poorly understood disorder, characterized by an involuntary muscular spasm of the pelvic floor muscles and outer third of the vagina during intercourse attempt, which results in aversion to penetration. It is reported to affect 1-7% of women worldwide. With this report the authors aim to describe the case of a young patient with vaginismus in whom techniques usually from the chronic pain domain were used as part of her multimodal therapeutic regimen.

  7. Insomnia in childhood and adolescence: clinical aspects, diagnosis, and therapeutic approach

    Directory of Open Access Journals (Sweden)

    Magda Lahorgue Nunes

    2015-11-01

    Full Text Available Objectives: To review the clinical characteristics, comorbidities, and management of insomnia in childhood and adolescence. Sources: This was a non-systematic literature review carried out in the PubMed database, from where articles published in the last five years were selected, using the key word “insomnia” and the pediatric age group filter. Additionally, the study also included articles and classic textbooks of the literature on the subject. Data synthesis: During childhood, there is a predominance of behavioral insomnia as a form of sleep-onset association disorder (SOAD and/or limit-setting sleep disorder. Adolescent insomnia is more associated with sleep hygiene problems and delayed sleep phase. Psychiatric (anxiety, depression or neurodevelopmental disorders (attention deficit disorder, autism, epilepsy frequently occur in association with or as a comorbidity of insomnia. Conclusions: Insomnia complaints in children and adolescents should be taken into account and appropriately investigated by the pediatrician, considering the association with several comorbidities, which must also be diagnosed. The main causes of insomnia and triggering factors vary according to age and development level. The therapeutic approach must include sleep hygiene and behavioral techniques and, in individual cases, pharmacological treatment. Resumo: Objetivos: Revisar as características clinicas, as comorbidades e o manejo da insônia na infância e adolescência. Fonte dos dados: Revisão não sistemática da literatura realizada na base dados PubMed,onde foram selecionados artigos publicados nos últimos 5 anos, selecionados com o uso da palavra chave insônia e o filtro faixa etária pediátrica. Adicionalmente foram também incluídos artigos e livros texto clássicos da literatura sobre o tema. Síntese dos dados: Na infância existe predomínio da insônia comportamental na forma de distúrbio de início do sono por associações inadequadas e

  8. The relationship between clinical findings and therapeutic approach in the treatment of fractured frontal sinus walls

    Directory of Open Access Journals (Sweden)

    Pešić Zoran

    2007-01-01

    Full Text Available Introduction The incidence of fractured frontal sinus walls vary from 6% to 12% of all craniofacial injuries. Objective Estimated relation between clinical findings and performed therapeutic procedures in treating fractured frontal sinus walls. To estimate success in performed therapeutic procedures, according to the incidence of postoperative complications and the integrity of injured regions from the functional and esthetical aspect. Method We analyzed, by retrospective clinical investigation, 19 patients with fractured frontal sinus walls and dislocated fragments, treated at the Department for Maxillofacial Surgery, Clinic of Dentistry in Niš, in the period March 1995 - March 2006. The success of therapy was estimated based on the incidence and type of complications and esthetical results in relation to preoperative findings. Results Predominant etiological factor in fractures of frontal sinus walls is trauma sustained in traffic accidents, which occurred in 52.6% of patients in our investigation. In clinical findings, the impression was the predominant sign, present in 16 patients. In 6 cases soft tissue access through already present lacerations or their extensions was employed, in 4 cases it was done by supraciliary access and in 9 by bicoronal access. As a therapeutic measure, drainage was performed in 5 cases, cranialisation in one, ostheoneogenetic access in 11 cases and a simple reposition of fragments in 2 patients with fractured frontal sinus walls. Infection as a complication was absent. All patients were satisfied with postoperative esthetical appearance of the injured region. Conclusion The infection, the lacerations and the direction of fractured lines are dominant factors in the determination of therapeutic procedures used to treat fractured frontal sinus walls. This will result in the low incidence of infection as a postoperative complication and in patient’s satisfaction with postoperative esthetical result of the injured

  9. Ivacaftor: A Novel Gene-Based Therapeutic Approach for Cystic Fibrosis

    OpenAIRE

    Condren, Michelle E.; Bradshaw, Marquita D.

    2013-01-01

    Ivacaftor is a new therapeutic agent that acts at the cystic fibrosis transmembrane conductance regulator (CFTR) channel to alter activity. It is approved for use in patients 6 years and older with cystic fibrosis who have at least 1 G551D mutation in the CFTR gene. It is unlike any other current pharmacologic agent for cystic fibrosis in that it specifically targets the gene defect associated with cystic fibrosis as opposed to treating resulting symptomology. Mucoactive agents, antibiotics, ...

  10. Breaching the Castle Walls: Hyaluronan-Depletion as a Therapeutic Approach to Cancer Therapy

    Directory of Open Access Journals (Sweden)

    H Michael eShepard

    2015-08-01

    Full Text Available Hyaluronan (HA has many functions in the extracellular milieu of normal and diseased tissues. Disease-associated HA accumulation has been shown to predict a worsened prognosis in cancer patients, with tumors having a high extracellular HA content (HA-high being more aggressive than their HA-low counterparts. HA-high tumor aggressiveness is derived from the specialized biomechanical and molecular properties of the HA-based assembly of HA binding proteins and the growth-promoting factors that accumulate in it. Biophysical characteristics of an HA-high tumor microenvironment include high tumor interstitial pressure, compression of tumor vasculature, and resulting tumor hypoxia. Within the tumor cell membrane, HA receptors, primarily CD44 and RHAMM, anchor the HA-high extracellular network. HA-CD44 association on the tumor cell surface enhances receptor tyrosine kinase activity to drive tumor progression and treatment resistance. Together, malignant cells in this HA-high matrix may evolve dependency on it for growth. This yields the hypothesis that depleting HA in HA-high tumors may be associated with a therapeutic benefit. A pegylated form of recombinant human hyaluronidase PH20 (PEGPH20 has been deployed as a potential cancer therapeutic in HA-high tumors. PEGPH20 can collapse this matrix by degrading the HA-assembled tumor extracellular framework, leading to tumor growth inhibition, preferentially in HA-high tumors. Enzymatic depletion of HA by PEGPH20 results in re-expansion of the tumor vasculature, reduction in tumor hypoxia, and increased penetration of therapeutic molecules into the tumor. Finally, HA depletion results in reduced signaling via CD44/RHAMM. Taken together, HA-depletion strategies accomplish their antitumor effects by multiple mechanisms that include targeting both biophysical and molecular signaling pathways. Ongoing clinical trials are examining the potential of PEGPH20 in combination with partner therapeutics in several

  11. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  12. [Clinical presentation, therapeutic approach and outcomes in acute poisoning treated with activated charcoal. Are there differences between men and women?].

    Science.gov (United States)

    Amigó-Tadín, Montserrat; Nogué-Xarau, Santiago; Miró-Andreu, Oscar

    2010-01-01

    To determine whether there are gender-based differences in the clinical presentation, therapeutic approaches and outcomes in acute poisoning treated with activated charcoal. A descriptive study conducted in the Emergency Department of the Hospital Clínic de Barcelona over the 7 years between the years 2001 and 2008. The study included poisoned patients who had received activated charcoal. The variables included, epidemiological data, clinical and toxicological presentation, therapeutic approach, time in emergency department and outcomes. A total of 575 patients were included in the study. The mean age was 37.8 (SD 14.8) years and 65.7% were females. No differences were observed between males and females with respect to age, number of drugs involved in the poisoning or the number of tablets ingested, but a higher prevalence of benzodiazepine poisoning was observed in females compared to males (69.8 vs. 61.2%; Ppoisoning was more common in males than in females (32.4 vs.18.8%; Ppoisoning was also more common in males than in females (7.9 vs. 3.2%; Ppoisonings, delays in care, hours of emergency department stay, treatment or outcome. Benzodiazepine poisoning was more prevalent in females than in males. Non-drug poisonings and alcohol combined with drug ingestion were more common in males. The clinical outcomes of the poisonings, delays in care, therapeutic requirements and admissions were similar between genders. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  13. [Multimodal therapeutic approach of vaginismus: an innovative approach through trigger point infiltration and pulsed radiofrequency of the pudendal nerve].

    Science.gov (United States)

    Carvalho, Joana Chaves Gonçalves Rodrigues de; Agualusa, Luís Miguel; Moreira, Luísa Manuela Ribeiro; Costa, Joana Catarina Monteiro da

    Vaginismus is a poorly understood disorder, characterized by an involuntary muscular spasm of the pelvic floor muscles and outer third of the vagina during intercourse attempt, which results in aversion to penetration. It is reported to affect 1-7% of women worldwide. With this report the authors aim to describe the case of a young patient with vaginismus in whom techniques usually from the chronic pain domain were used as part of her multimodal therapeutic regimen. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  14. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.

    Science.gov (United States)

    Schaeffer, Evelin L; Forlenza, Orestes V; Gattaz, Wagner F

    2009-01-01

    Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.

  15. Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.

    Science.gov (United States)

    Carmeli, Y; Akova, M; Cornaglia, G; Daikos, G L; Garau, J; Harbarth, S; Rossolini, G M; Souli, M; Giamarellou, H

    2010-02-01

    Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

  16. Radiation protection for innovative diagnostic and therapeutic approaches in nuclear medicine

    International Nuclear Information System (INIS)

    Aubert, B.; Chatal, J.F.

    2006-01-01

    A real technological revolution has deeply modified the field of application and perspectives of nuclear medicine, and nuclear oncology in particular, during the past 5 years. Diagnostic applications such as positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) have had a significant impact on the diagnostic strategy adopted by medical oncologists, with the addition of invaluable functional data to already available anatomical data provided by conventional imaging modalities. Numerous other 18 F-labeled tracers currently under clinical evaluation have been developed to study various tumor functions (tumor proliferation, hypoxia, hemo-therapy-induced apoptosis, etc.). These tracers may have a considerable impact on therapeutic strategies. Other positron-emitting radionuclides, such as copper-64, iodine-124, and yttrium-86 (whose respective half-lives are 12.7 hours, 4.2 days. and 14.7 hours) will soon be available for certain clinical indications, such as immuno-PET (with monoclonal antibodies or antibody fragments used as carriers) or pretreatment dosimetry, which cannot be performed with fluorine-18 due its short half-life. As far as therapeutic applications are concerned, the use of internal radiotherapy, which has been restricted to thyroid cancer for a long time, was recently extended to other cancers as new carriers, such as monoclonal antibodies (radioimmunotherapy) or peptides (radio-peptide therapy), new targeting methods (pre-targeting), and new radionuclides, especially alpha particle emitters (alpha therapy), became available. These technological advances require that specific radiation safety regulations be implemented to protect nuclear medicine personnel, patients' close relatives, and the environment. Most current regulations concern diagnostic applications with technetium-99m and therapeutic applications with iodine-131. Regulations pertaining to the clinical use of 18 F-FDG were recently enacted (2001). Regarding exposure nuclear

  17. Recent progress of diagnostic and therapeutic approach to cancers using polyclonal or monoclonal antibodies

    International Nuclear Information System (INIS)

    Koji, Toshihiko

    1982-01-01

    Among the major topics of interest in cancer immunology, immunodiagnosis and immunotherapy with the antibodies are summarized historically and prospectively. The concept of injecting anti-tumor cell antibodies to localize tumors was first introduced in experimental systems by Pressman (1957). Since then, various trials have been achieved with human tumors using specific or nonspecific tumor-localizing antibodies diagnostically or therapeutically. In 1970's, successes in immunodiagnosis with the antibodies to oncofetal proteins also have been reported. Recently, there are numerous papers dealed with a series of external scanning or serotherapeutic trials by the use of monoclonal antibodies that bind selectively to tumor cells. Various relevant problems with them are discussed. (author)

  18. Angioedema hereditário: considerações sobre terapia Therapeutic approach of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Kélem de Nardi Chagas

    2004-09-01

    HAE ser causado pelo mesmo defeito e acometer membros da mesma família, diferentes critérios têm sido estabelecidos para o tratamento desses pacientes. Foram indicados diferentes esquemas terapêuticos para HAE e alguns dos pacientes puderam ser seguidos sem terapia medicamentosa.PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1-INH. Treatment is indicated for acute attacks or prophylaxis of angioedema which occur in the subcutaneous tissue respiratory or gastrointestinal tracts. Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen, like tranexamic acid or e-aminocaproic acid and the administration of C1-INH concentrate. We describe the peculiarities of the treatment chosen for 10 patients (4 families with HAE and their evolution. METHODS: Ten patients (1-38 years old with HAE were diagnosed by clinical history and laboratory evaluation. The following tests were performed for the complement system: C1-INH, C4 and C3 levels and hemolytic assay (CH50 and APH50 for the classic and alternative pathways. Treatment was initiated considering severity of symptoms, age, gender and therapeutic response of the patient. RESULTS: Clinical evaluation showed: 4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal edema and 3/10 with sporadic symptoms. Different severity of symptoms was verified in the same family. The laboratory evaluation detected: low C1-INH levels (10/10; low serum C4 level (8/10; undetectable CH50 (3/10 and low CH50 levels (6/10; low APH50 levels (2/10. Six out of ten patients did not receive any specific treatment and 2 of them had high risk of asphyxia. One adolescent had been controlled with e-aminocaproic acid, one child had been changed from danazol to tranexamic acid, a 30 year old female patient had received oxandrolone and a 38 year old man had been treated with danazol. CONCLUSIONS: Although

  19. The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Irina Gavrilovskaya

    2012-01-01

    Full Text Available American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS. Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

  20. Non-Clinical Models for Neurodegenerative Diseases: Therapeutic Approach and Drug Validation in Animal Models

    Directory of Open Access Journals (Sweden)

    Caridad Ivette Fernandez

    2017-12-01

    Full Text Available In 2016, 19.8% of the Cuban population was aged 60 or over. As a result, age-associated degenerative diseases and other diseases have become priority targets from a prophylactic, diagnostic and therapeutic perspective. As a result, the Cuban biomedical scientific community has addressed its basic, preclinical and epidemiological research in order to rise up to the challenge. A firm step in this direction has been the international congress “State of the art in non-clinical models for neurodegenerative diseases” which has brought together preclinical and clinical researchers, technicians and regulatory staff members from different countries to review the state of the art in neurodegenerations, find unifying ideas, objectives and collaborations or partnership. The objective is to expose the perspectives of new biotechnological products from Cuba and other countries from the diagnostic, therapeutic and neuroprotective point of view. It is crucial, therefore, that the irreplaceable role of laboratory animals in achieving these objectives is understood but they must be used in rational, adequate and ethical manner. We expose the current development trends in this field, being of common interest to the work directed to the search for potential drugs, diagnostic tools and the promotion of changes in lifestyle as a preventive projection.

  1. Pelvic floor muscle rehabilitation for patients with lifelong premature ejaculation: a novel therapeutic approach.

    Science.gov (United States)

    Pastore, Antonio L; Palleschi, Giovanni; Fuschi, Andrea; Maggioni, Cristina; Rago, Rocco; Zucchi, Alessandro; Costantini, Elisabetta; Carbone, Antonio

    2014-06-01

    Premature ejaculation is the most common male sexual disorder. The aim of the study was to evaluate the possible therapeutic role of pelvic floor muscle rehabilitation in patients affected by lifelong premature ejaculation. We treated 40 men with lifelong premature ejaculation, reporting, a baseline intravaginal ejaculatory latency time (IELT) ≤ 1 min, with 12-week pelvic floor muscle rehabilitation. At the end of the rehabilitation, mean IELTs were calculated to evaluate the effectiveness of the therapy. At the end of the treatment, 33 (82.5%) of the 40 patients gained control of their ejaculatory reflex, with a mean IELT of 146.2 s (range: 123.6-152.4 s). A total of 13 out of 33 (39%) patients were evaluated at 6 months follow up, and they maintained a significant IELT (112.6 s) compared with their initial IELT (mean 39.8 s). The results obtained in our subjects treated with pelvic floor rehabilitation are promising. This therapy represents an important cost reduction compared with the standard treatment (selective serotonin reuptake inhibitors). Based on the present data, we propose pelvic floor muscle rehabilitation as a new, viable therapeutic option for the treatment of premature ejaculation.

  2. Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach.

    Science.gov (United States)

    Franquesa, Alba; Sainz-Cort, Alberto; Gandy, Sam; Soler, Joaquim; Alcázar-Córcoles, Miguel Ángel; Bouso, José Carlos

    2018-04-04

    Ayahuasca is a psychedelic decoction originating from Amazonia. The ayahuasca-induced introspective experience has been shown to have potential benefits in the treatment of several pathologies, to protect mental health and to improve neuropsychological functions and creativity, and boost mindfulness. The underlying psychological processes related to the use of ayahuasca in a psychotherapeutic context are not yet well described in the scientific literature, but there is some evidence to suggest that psychological variables described in psychotherapies could be useful in explaining the therapeutic effects of the brew. In this study we explore the link between ayahuasca use and Decentering, Values and Self, comparing subjects without experience of ayahuasca (n = 41) with subjects with experience (n = 81). Results confirm that ayahuasca users scored higher than non-users in Decentering and Positive self, but not in Valued living, Life fulfillment, Self in social relations, Self in close relations and General self. Scores in Decentering were higher in the more experienced subjects (more than 15 occasions) than in those with less experience (less than 15 occasions). Our results show that psychological process variables may explain the outcomes in ayahuasca psychotherapy. The introduction of these variables is warranted in future ayahuasca therapeutic studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Therapeutic Significance of Loligo vulgaris (Lamarck, 1798) ink Extract: A Biomedical Approach

    Science.gov (United States)

    Nadarajah, Sri Kumaran; Vijayaraj, Radha; Mani, Jayaprakashvel

    2017-01-01

    Background: The squid ink extract is well known for its biomedical properties. Objective: In this study, squid Loligo vulgaris was collected from Tuticorin costal water, Bay of Bengal, India. Materials and Methods: Proximate composition of the crude squid ink was studied and found to have protein as the major component over lipid and carbohydrates. Further, bioactive fractions of squid ink were extracted with ethanol, and therapeutic applications such as hemolytic, antioxidant, antimicrobial, and in vitro anti-inflammatory properties were analyzed using standard methods. Results: In hemolytic assay, the squid ink extract exhibited a maximum hemolytic activity of 128 hemolytic unit against tested erythrocytes. In DPPH assay, the ethanolic extract of squid ink has exhibited an antioxidant activity of 83.5%. The squid ink was found to be potent antibacterial agent against the pathogens tested. 200 μL of L. vulgaris ink extract showed remarkable antibacterial activity as zone of inhibition against Escherichia coli (28 mm), Klebsiella pneumoniae (22 mm), Pseudomonas aeruginosa (21 mm), and Staphylococcus aureus (24 mm). The 68.9% inhibition of protein denaturation by the squid ink extract indicated that it has very good in vitro anti-inflammatory properties. The Fourier transform infrared spectroscopy analysis of the ethanolic extracts of the squid ink indicated the presence of functional groups such as 1° and 2° amines, amides, alkynes (terminal), alkenes, aldehydes, nitriles, alkanes, aliphatic amines, carboxylic acids, and alkyl halides, which complements the biochemical background of therapeutic applications. Conclusion: Hence, results of this study concluded that the ethanolic extract of L. vulgaris has many therapeutic applications such as antimicrobial, antioxidant, and anti-inflammatory activities. SUMMARY Squid ink is very high in a number of important nutrients. It’s particularly high in antioxidants for instance, which as well all know help to protect

  4. Switchgrass a valuable biomass crop for energy

    CERN Document Server

    2012-01-01

    The demand of renewable energies is growing steadily both from policy and from industry which seeks environmentally friendly feed stocks. The recent policies enacted by the EU, USA and other industrialized countries foresee an increased interest in the cultivation of energy crops; there is clear evidence that switchgrass is one of the most promising biomass crop for energy production and bio-based economy and compounds. Switchgrass: A Valuable Biomass Crop for Energy provides a comprehensive guide to  switchgrass in terms of agricultural practices, potential use and markets, and environmental and social benefits. Considering this potential energy source from its biology, breed and crop physiology to its growth and management to the economical, social and environmental impacts, Switchgrass: A Valuable Biomass Crop for Energy brings together chapters from a range of experts in the field, including a foreword from Kenneth P. Vogel, to collect and present the environmental benefits and characteristics of this a ...

  5. BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Da Costa, D; Agathanggelou, A; Perry, T; Weston, V; Petermann, E; Zlatanou, A; Oldreive, C; Wei, W; Stewart, G; Longman, J; Smith, E; Kearns, P; Knapp, S; Stankovic, T

    2013-01-01

    Paediatric B-precursor ALL is a highly curable disease, however, treatment resistance in some patients and the long-term toxic effects of current therapies pose the need for more targeted therapeutic approaches. We addressed the cytotoxic effect of JQ1, a highly selective inhibitor against the transcriptional regulators, bromodomain and extra-terminal (BET) family of proteins, in paediatric ALL. We showed a potent in vitro cytotoxic response of a panel of primary ALL to JQ1, independent of their prognostic features but dependent on high MYC expression and coupled with transcriptional downregulation of multiple pro-survival pathways. In agreement with earlier studies, JQ1 induced cell cycle arrest. Here we show that BET inhibition also reduced c-Myc protein stability and suppressed progression of DNA replication forks in ALL cells. Consistent with c-Myc depletion and downregulation of pro-survival pathways JQ1 sensitised primary ALL samples to the classic ALL therapeutic agent dexamethasone. Finally, we demonstrated that JQ1 reduces ALL growth in ALL xenograft models, both as a single agent and in combination with dexamethasone. We conclude that targeting BET proteins should be considered as a new therapeutic strategy for the treatment of paediatric ALL and particularly those cases that exhibit suboptimal responses to standard treatment

  6. Vulnerability of particularly valuable areas. Summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    This report is part of the scientific basis for the management plan for the North Sea and Skagerrak. The report focuses on the vulnerability of particularly valuable areas to petroleum activities, maritime transport, fisheries, land-based and coastal activities and long-range transboundary pollution. A working group with representatives from many different government agencies, headed by the Institute of Marine Research and the Directorate for Nature Management, has been responsible for drawing up the present report on behalf of the Expert Group for the North Sea and Skagerrak. The present report considers the 12 areas that were identified as particularly valuable during an earlier stage of the management plan process on the environment, natural resources and pollution. There are nine areas along the coast and three open sea areas in the North Sea that were identified according to the same predefined criteria as used for the management plans for the Barents Sea: Lofoten area and the Norwegian Sea. The most important criteria for particularly valuable areas are importance for biological production and importance for biodiversity.(Author)

  7. Vulnerability of particularly valuable areas. Summary

    International Nuclear Information System (INIS)

    2012-01-01

    This report is part of the scientific basis for the management plan for the North Sea and Skagerrak. The report focuses on the vulnerability of particularly valuable areas to petroleum activities, maritime transport, fisheries, land-based and coastal activities and long-range transboundary pollution. A working group with representatives from many different government agencies, headed by the Institute of Marine Research and the Directorate for Nature Management, has been responsible for drawing up the present report on behalf of the Expert Group for the North Sea and Skagerrak. The present report considers the 12 areas that were identified as particularly valuable during an earlier stage of the management plan process on the environment, natural resources and pollution. There are nine areas along the coast and three open sea areas in the North Sea that were identified according to the same predefined criteria as used for the management plans for the Barents Sea: Lofoten area and the Norwegian Sea. The most important criteria for particularly valuable areas are importance for biological production and importance for biodiversity.(Author)

  8. Development of new therapeutic methods of lung cancer through team approach study (II)

    International Nuclear Information System (INIS)

    Zo, Jae Ill; Park, Jong Ho; Baek, Hee Jong

    1999-12-01

    The aims of this study were to make the lung cancer clinics in Korea Cancer Center Hospital, and to establish new therapeutic methods of lung cancer for increasing the cure rate and survival rate of patients. Also another purpose of this study was to establish a common treatment method in our hospital. All patients who were operated in Korea Cancer Center Hospital from 1987 due to lung cancer were followed up and evaluated. And we have been studied the effect of postoperative adjuvant therapy in stage 1, 2, 3A non-small cell lung cancer patients from 1989 with the phase three study form. Follow-up examinations were scheduled in these patients and interim analysis was made. Also we have been studied the effect of chemotherapeutic agents in small cell lung cancer patients from 1997 with the phase two study form. We evaluated the results of this study

  9. Combined approach with therapeutic drug monitoring and pharmacogenomics in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    S Manvizhi

    2013-01-01

    Full Text Available In patients undergoing renal transplantation, dose individualization for tacrolimus is routinely achieved with therapeutic drug monitoring (TDM. The patient started on 5.5 mg/day of tacrolimus had a significantly elevated tacrolimus trough concentration. The tacrolimus dose was regularly reduced following TDM at many time periods in the post transplant period but the tacrolimus concentration was consistently elevated. Genomic analysis done after four years revealed mutations in the genes encoding for CYP3A5 and MDR1 (2677G > T. Pharmacogenomics alongside TDM, will soon emerge as the backbone of dose individualization. But for genomics to be beneficial, it should be advocated in the pre-transplant or early post transplant period.

  10. Sclerosing Angiomatoid Nodular Transformation: Laparoscopic Splenectomy as Therapeutic and Diagnostic Approach at the Same Time

    Directory of Open Access Journals (Sweden)

    Calogero Cipolla

    2018-01-01

    Full Text Available Introduction. Sclerosing angiomatoid nodular transformation (SANT of the spleen is a rare benign vascular lesion with unknown etiopathogenesis and with definite features of imaging, histopathology, and immunohistochemistry. It was first described by Martel et al. in 2004, and to date, only 151 cases have been reported. Case Description. We report a case of SANT of the spleen detected in a 66-year-old Caucasian, without comorbidities, presented to our department with epigastric pain. We, also, presented a review of the literature. Conclusions. SANT is a benign incidentally vascular condition in the majority of cases. The wide age and gender distribution in our review is in accordance with that in previous studies in English literature. In our opinion, splenectomy is the choice treatment because it is at the same time diagnostic and therapeutic in a definitive way.

  11. Sclerosing Angiomatoid Nodular Transformation: Laparoscopic Splenectomy as Therapeutic and Diagnostic Approach at the Same Time.

    Science.gov (United States)

    Cipolla, Calogero; Florena, Ada Maria; Ferrara, Gabriella; Di Gregorio, Riccardo; Unti, Elettra; Giannone, Antonino G; Lazzaro, Luigi A; Graceffa, Giuseppa; Pantuso, Gianni

    2018-01-01

    Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare benign vascular lesion with unknown etiopathogenesis and with definite features of imaging, histopathology, and immunohistochemistry. It was first described by Martel et al. in 2004, and to date, only 151 cases have been reported. We report a case of SANT of the spleen detected in a 66-year-old Caucasian, without comorbidities, presented to our department with epigastric pain. We, also, presented a review of the literature. SANT is a benign incidentally vascular condition in the majority of cases. The wide age and gender distribution in our review is in accordance with that in previous studies in English literature. In our opinion, splenectomy is the choice treatment because it is at the same time diagnostic and therapeutic in a definitive way.

  12. Oral Lichen Planus in a Pediatric Patient: A Novel Therapeutic Approach

    Science.gov (United States)

    Sharma, Gaurav; Vohra, Puneeta; Rehani, Shweta; Nagpal, Archna

    2017-01-01

    Lichen planus is a mucocutaneous disease, predominantly affecting the middle-aged individuals and may be associated with a plethora of signs and symptoms related to the skin, scalp, nails and mucous membranes. The definitive etiology of lichen planus is not yet known and no therapeutic modality has yet been universally accepted. Lichen planus in pediatric patients is a rare phenomenon and its presence in the oral mucosa is even rarer. The aim of this article is to present a rare case of a symptomatic oral lichen planus (OLP) occurring in a 12-year old child that was managed successfully with a novel sequential modality of topical retinoids followed by aloe vera gel application. PMID:29104603

  13. Oral Lichen Planus in a Pediatric Patient: A Novel Therapeutic Approach.

    Science.gov (United States)

    Sharma, Gaurav; Sardana, Divesh; Vohra, Puneeta; Rehani, Shweta; Nagpal, Archna

    2017-03-01

    Lichen planus is a mucocutaneous disease, predominantly affecting the middle-aged individuals and may be associated with a plethora of signs and symptoms related to the skin, scalp, nails and mucous membranes. The definitive etiology of lichen planus is not yet known and no therapeutic modality has yet been universally accepted. Lichen planus in pediatric patients is a rare phenomenon and its presence in the oral mucosa is even rarer. The aim of this article is to present a rare case of a symptomatic oral lichen planus (OLP) occurring in a 12-year old child that was managed successfully with a novel sequential modality of topical retinoids followed by aloe vera gel application.

  14. Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP).

    Science.gov (United States)

    Brennan, Tracy A; Lindborg, Carter M; Bergbauer, Christian R; Wang, Haitao; Kaplan, Frederick S; Pignolo, Robert J

    2018-04-01

    Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies. Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Cromolyn, but not aprepitant, significantly decreases the total number of mast cells in FOP lesions. Furthermore, cromolyn specifically diminishes the number of degranulating and resting degranulated mast cells in pre-osseous lesions. This work demonstrates that consideration of FOP as a type of localized mastocytosis may offer new therapeutic interventions for treatment of this devastating condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Statins as a new therapeutic approach in dedifferentiated thyroid cancer? A case report

    International Nuclear Information System (INIS)

    Hofmann, A.; John, P.; Sinzinger, H.; Staudenherz, A.; Schaffarich, M.P.

    2005-01-01

    Full text: In general differentiated thyroid tumours are removed surgically and afterwards treated with radioiodine. However, still about one third of patients with differentiated tumours, metastasise. Also 30 percent of recurrent thyroid carcinomas do not respond to iodine treatment due to loss of differentiation. Retinoic acid, biological metabolites of vitamin A, are considered to induce re-differentiation of the thyrocyte and thereby induce tumor regression. In follicular carcinoma cells, it also plays an important role in inducing iodine uptake. Retinoids, however, cannot be used in liver disease as they may induce hepatic enzyme increase. In addition 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are reported to induce on the one hand cellular apoptosis and on the other hand, in a lower dosage, differentiation in anaplastic thyroid carcinoma cells in vitro. We are presenting a 79 years old female patient with an oxyphilic follicular thyroid carcinoma and histologically verified autoimmune hepatitis. The first post therapeutic scan, showed only focal cervical localized iodine uptake. Also 3 months later no pathologic iodine uptake was recognized on the diagnostic scan, whereas the FDG-PET showed solid uptake of FDG cervical, in both lungs, in the mediastinum, the pelvis and the right hip. Due to contraindication for retinoic acid the patient was treated with usual dose statin for about 4 weeks to induce re-differentiation. Following, the patient was administered 9,25 GBq I-131 again and the post therapeutic scan showed iodine uptake cervical and in the right femur. We conclude that the administration of Statins, at low dose (20 mg/day) even over a short period of time, only may induce re-differentiation as well as an antiproliferative effect in vivo. (author)

  16. Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach.

    Directory of Open Access Journals (Sweden)

    Christoph Jindra

    Full Text Available Persistent infection with high-risk human papillomavirus (HPV types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c. prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease.

  17. Self-inflicted skin lesions: the importance of a proper diagnostic and therapeutic approach

    Directory of Open Access Journals (Sweden)

    Dimitre Dimitrov

    2016-12-01

    Full Text Available Introduction . Patients with self-inflicted skin lesions (SISL are most often referred to dermatologists. Since psychological and psychiatric conditions might be the underlying reasons for the behavior of these patients, the psychology-associated component should always be kept in mind when approaching such individuals. Objective. To discuss distinctive aspects of the approach towards patients with SISL and emphasize the most relevant issues concerning the management of psychodermatoses. Case report. We present a case of a 13-year-old girl with a 6-month history of skin lesions misdiagnosed as allergic contact dermatitis. Conscientious history taking and physical examination enabled the diagnosis of SISL. Conclusions. The proper approach to patients presenting with psychodermatoses differs from that for other dermatological patients and requires considering several additional aspects. We would like to emphasize the distinguishing aspects and importance of the proper approach to patients with SISL that might aid clinicians in diagnosing and treating these individuals in the future.

  18. Self-inflicted skin lesions: the importance of a proper diagnostic and therapeutic approach

    OpenAIRE

    Dimitre Dimitrov; Radomir Reszke; Jacek Szepietowski

    2016-01-01

    Introduction . Patients with self-inflicted skin lesions (SISL) are most often referred to dermatologists. Since psychological and psychiatric conditions might be the underlying reasons for the behavior of these patients, the psychology-associated component should always be kept in mind when approaching such individuals. Objective. To discuss distinctive aspects of the approach towards patients with SISL and emphasize the most relevant issues concerning the management of psychodermatose...

  19. Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

    Directory of Open Access Journals (Sweden)

    Tania Martins-Marques

    2016-09-01

    Full Text Available Extracellular vesicles (EVs are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox, presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43 in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects.

  20. From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins

    Directory of Open Access Journals (Sweden)

    Aida Verdes

    2016-04-01

    Full Text Available Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1 delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2 identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3 chemical and recombinant synthesis of promising peptide toxins; (4 structural characterization through experimental and computational methods; (5 determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6 optimization of peptide toxin affinity and selectivity to molecular target; and (7 development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

  1. Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in vivo.

    Science.gov (United States)

    Stenner, Frank; Liewen, Heike; Zweifel, Martin; Weber, Achim; Tchinda, Joelle; Bode, Beata; Samaras, Panagiotis; Bauer, Stefan; Knuth, Alexander; Renner, Christoph

    2008-09-01

    Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies, being responsible for the majority of thyroid cancer-related deaths. Despite multimodal therapy including surgery, chemotherapy, and radiotherapy, the outcome of ATC is poor. The human ATC cell line MB1, derived from tumor tissue of a 57-year-old man with thyroid cancer and pronounced neutrophilia, was established from surgically excised tumor tissue. The karyotype of the cell line shows many chromosomal abnormalities. Preclinical investigations have shown antitumor activity and effectiveness of the BRAF kinase inhibitor Sorafenib and the proteasome inhibitor Bortezomib. After establishment of the MB1 cell line these agents were applied in vitro and, showing activity in a cell culture model, were also used for in vivo treatment. Sorafenib had some clinical effect, namely normalization of leucocytosis, but had no sustained impact on subsequent tumor growth and development of distant metastasis. Molecular diagnostics of the tumor demonstrated no BRAF mutations in exons 11 and 15 concordant with a rather modest effect of Sorafenib on MB1 cell growth. Clinical benefit was seen with subsequent bortezomib therapy inducing a temporary halt to lymph node growth and a progression-free interval of 7 weeks. Our observations together with previous data from preclinical models could serve as a rationale for selecting those patients suffering from ATC most likely to benefit from targeted therapy. A prospective controlled randomized trial integrating kinase and proteasome inhibitors into a therapeutic regime for ATC is warranted.

  2. Recurrent parotid swelling secondary to masseter muscle hypertrophy: a multidisciplinary diagnostic and therapeutic approach.

    Science.gov (United States)

    Capaccio, Pasquale; Gaffuri, Michele; Pignataro, Lorenzo; Assandri, Fausto; Pereira, Pollyanna; Farronato, Giampietro

    2016-11-01

    To present a patient with an atypical recurrent parotid swelling due to masseter muscle hypertrophy and the diagnostic/therapeutic assessment to treat this condition. A patient referring recurrent right facial swelling underwent a complete multidisciplinary assessment of the parotid region that revealed masseter muscle hypertrophy, confirmed by means of clinical (otolaryngological and gnathological evaluation), radiological (utrasonography, dynamic magnetic resonance imaging, and cone beam computed tomography), instrumental (electromyography to evaluate the right masseter muscle function and kinesiography to evaluate maximum right deflection - MaxRDefl and maximum opening - MaxMO) and sialendoscopy assessment where T0 indicates the pre-treatment values. All electromyographic and kinesiographic parameters were evaluated six months after the orthodontic application of a neuromuscular orthosis at T1. At T1, the effectiveness of the orthodontic therapy was demonstrated by the complete resolution of symptoms, and instrumental results documented more efficient muscle activity at rest and during clenching and a better mandibular position. At EMG T1, the resting and post-TENS values were, respectively, 1.2 and 1.8 microV. At kinesiography, MaxRDefl increased from 10.2 (T0) to 10.5 mm (T1); maxMO increased from 41.2 (T0) to 48 mm (T1). The proposed multidisciplinary assessment based on otolaryngological, gnathological, and radiological evaluation may be useful in the case of recurrent parotid swelling secondary to masseter muscle hypertrophy to plan an appropriate management with a removable neuromuscular orthosis.

  3. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis.

    Science.gov (United States)

    Bronckaers, Annelies; Hilkens, Petra; Martens, Wendy; Gervois, Pascal; Ratajczak, Jessica; Struys, Tom; Lambrichts, Ivo

    2014-08-01

    Mesenchymal stem cells or multipotent stromal cells (MSCs) have initially captured attention in the scientific world because of their differentiation potential into osteoblasts, chondroblasts and adipocytes and possible transdifferentiation into neurons, glial cells and endothelial cells. This broad plasticity was originally hypothesized as the key mechanism of their demonstrated efficacy in numerous animal models of disease as well as in clinical settings. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly caused by the multitude of bioactive molecules secreted by these remarkable cells. Numerous angiogenic factors, growth factors and cytokines have been discovered in the MSC secretome, all have been demonstrated to alter endothelial cell behavior in vitro and induce angiogenesis in vivo. As a consequence, MSCs have been widely explored as a promising treatment strategy in disorders caused by insufficient angiogenesis such as chronic wounds, stroke and myocardial infarction. In this review, we will summarize into detail the angiogenic factors found in the MSC secretome and their therapeutic mode of action in pathologies caused by limited blood vessel formation. Also the application of MSC as a vehicle to deliver drugs and/or genes in (anti-)angiogenesis will be discussed. Furthermore, the literature describing MSC transdifferentiation into endothelial cells will be evaluated critically. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: A New Therapeutic Approach

    International Nuclear Information System (INIS)

    Muñoz, Miguel; Coveñas, Rafael

    2015-01-01

    Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert an antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC

  5. A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches

    Directory of Open Access Journals (Sweden)

    John G. Bruno

    2013-03-01

    Full Text Available The potential to emulate or enhance antibodies with nucleic acid aptamers while lowering costs has prompted development of new aptamer-protein, siRNA, drug, and nanoparticle conjugates. Specific focal points of this review discuss DNA aptamers covalently bound at their 3' ends to various proteins for enhanced stability and greater pharmacokinetic lifetimes in vivo. The proteins can include Fc tails of IgG for opsonization, and the first component of complement (C1q to trigger complement-mediated lysis of antibiotic-resistant Gram negative bacteria, cancer cells and possibly some parasites during vulnerable stages. In addition, the 3' protein adduct may be a biotoxin, enzyme, or may simply be human serum albumin (HSA or a drug known to bind HSA, thereby retarding kidney and other organ clearance and inhibiting serum exonucleases. In this review, the author summarizes existing therapeutic aptamer conjugate categories and describes his patented concept for PCR-based amplification of double-stranded aptamers followed by covalent attachment of proteins or other agents to the chemically vulnerable overhanging 3' adenine added by Taq polymerase. PCR amplification of aptamers could dramatically lower the current $2,000/gram cost of parallel chemical oligonucleotide synthesis, thereby enabling mass production of aptamer-3'-protein or drug conjugates to better compete against expensive humanized monoclonal antibodies.

  6. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: A New Therapeutic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Miguel, E-mail: mmunoz@cica.es [Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, 41013 Sevilla (Spain); Coveñas, Rafael [Laboratory of Neuroanatomy of the Peptidergic System (Lab. 14), Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, 37008 Salamanca (Spain)

    2015-07-06

    Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)—at high concentrations—is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert an antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC.

  7. Muscle–Bone Crosstalk: Emerging Opportunities for Novel Therapeutic Approaches to Treat Musculoskeletal Pathologies

    Directory of Open Access Journals (Sweden)

    Delphine B. Maurel

    2017-10-01

    Full Text Available Osteoporosis and sarcopenia are age-related musculoskeletal pathologies that often develop in parallel. Osteoporosis is characterized by a reduced bone mass and an increased fracture risk. Sarcopenia describes muscle wasting with an increasing risk of injuries due to falls. The medical treatment of both diseases costs billions in health care per year. With the impact on public health and economy, and considering the increasing life expectancy of populations, more efficient treatment regimens are sought. The biomechanical interaction between both tissues with muscle acting on bone is well established. Recently, both tissues were also determined as secretory endocrine organs affecting the function of one another. New exciting discoveries on this front are made each year, with novel signaling molecules being discovered and potential controversies being described. While this review does not claim completeness, it will summarize the current knowledge on both the biomechanical and the biochemical link between muscle and bone. The review will highlight the known secreted molecules by both tissues affecting the other and finish with an outlook on novel therapeutics that could emerge from these discoveries.

  8. Combined Dynamic Light Scattering and Raman Spectroscopy Approach for Characterizing the Aggregation of Therapeutic Proteins

    Directory of Open Access Journals (Sweden)

    E. Neil Lewis

    2014-12-01

    Full Text Available Determination of the physicochemical properties of protein therapeutics and their aggregates is critical for developing formulations that enhance product efficacy, stability, safety and manufacturability. Analytical challenges are compounded for materials: (1 that are formulated at high concentration, (2 that are formulated with a variety of excipients, and (3 that are available only in small volumes. In this article, a new instrument is described that measures protein secondary and tertiary structure, as well as molecular size, over a range of concentrations and formulation conditions of low volume samples. Specifically, characterization of colloidal and conformational stability is obtained through a combination of two well-established analytical techniques: dynamic light scattering (DLS and Raman spectroscopy, respectively. As the data for these two analytical modalities are collected on the same sample at the same time, the technique enables direct correlation between them, in addition to the more straightforward benefit of minimizing sample usage by providing multiple analytical measurements on the same aliquot non-destructively. The ability to differentiate between unfolding and aggregation that the combination of these techniques provides enables insights into underlying protein aggregation mechanisms. The article will report on mechanistic insights for aggregation that have been obtained from the application of this technique to the characterization of lysozyme, which was evaluated as a function of concentration and pH.

  9. Muscle-Bone Crosstalk: Emerging Opportunities for Novel Therapeutic Approaches to Treat Musculoskeletal Pathologies.

    Science.gov (United States)

    Maurel, Delphine B; Jähn, Katharina; Lara-Castillo, Nuria

    2017-10-24

    Osteoporosis and sarcopenia are age-related musculoskeletal pathologies that often develop in parallel. Osteoporosis is characterized by a reduced bone mass and an increased fracture risk. Sarcopenia describes muscle wasting with an increasing risk of injuries due to falls. The medical treatment of both diseases costs billions in health care per year. With the impact on public health and economy, and considering the increasing life expectancy of populations, more efficient treatment regimens are sought. The biomechanical interaction between both tissues with muscle acting on bone is well established. Recently, both tissues were also determined as secretory endocrine organs affecting the function of one another. New exciting discoveries on this front are made each year, with novel signaling molecules being discovered and potential controversies being described. While this review does not claim completeness, it will summarize the current knowledge on both the biomechanical and the biochemical link between muscle and bone. The review will highlight the known secreted molecules by both tissues affecting the other and finish with an outlook on novel therapeutics that could emerge from these discoveries.

  10. Antisense Oligonucleotide-mediated Exon Skipping as a Systemic Therapeutic Approach for Recessive Dystrophic Epidermolysis Bullosa.

    Science.gov (United States)

    Bremer, Jeroen; Bornert, Olivier; Nyström, Alexander; Gostynski, Antoni; Jonkman, Marcel F; Aartsma-Rus, Annemieke; van den Akker, Peter C; Pasmooij, Anna Mg

    2016-10-18

    The "generalized severe" form of recessive dystrophic epidermolysis bullosa (RDEB-gen sev) is caused by bi-allelic null mutations in COL7A1, encoding type VII collagen. The absence of type VII collagen leads to blistering of the skin and mucous membranes upon the slightest trauma. Because most patients carry exonic point mutations or small insertions/deletions, most exons of COL7A1 are in-frame, and low levels of type VII collagen already drastically improve the disease phenotype, this gene seems a perfect candidate for antisense oligonucleotide (AON)-mediated exon skipping. In this study, we examined the feasibility of AON-mediated exon skipping in vitro in primary cultured keratinocytes and fibroblasts, and systemically in vivo using a human skin-graft mouse model. We show that treatment with AONs designed against exon 105 leads to in-frame exon 105 skipping at the RNA level and restores type VII collagen protein production in vitro. Moreover, we demonstrate that systemic delivery in vivo induces de novo expression of type VII collagen in skin grafts generated from patient cells. Our data demonstrate strong proof-of-concept for AON-mediated exon skipping as a systemic therapeutic strategy for RDEB.

  11. Live-Cell Imaging of Protease Activity: Assays to Screen Therapeutic Approaches.

    Science.gov (United States)

    Chalasani, Anita; Ji, Kyungmin; Sameni, Mansoureh; Mazumder, Samia H; Xu, Yong; Moin, Kamiar; Sloane, Bonnie F

    2017-01-01

    Methodologies to image and quantify the activity of proteolytic enzymes have been developed in an effort to identify protease-related druggable pathways that are involved in malignant progression of cancer. Our laboratory has pioneered techniques for functional live-cell imaging of protease activity in pathomimetic avatars for breast cancer. We analyze proteolysis in the context of proliferation and formation of structures by tumor cells in 3-D cultures over time (4D). In order to recapitulate the cellular composition and architecture of tumors in the pathomimetic avatars, we include other tumor-associated cells (e.g., fibroblasts, myoepithelial cells, microvascular endothelial cells). We also model noncellular aspects of the tumor microenvironment such as acidic pericellular pH. Use of pathomimetic avatars in concert with various types of imaging probes has allowed us to image, quantify, and follow the dynamics of proteolysis in the tumor microenvironment and to test interventions that impact directly or indirectly on proteolytic pathways. To facilitate use of the pathomimetic avatars for screening of therapeutic modalities, we have designed and fabricated custom 3D culture chambers with multiple wells that are either individual or connected by a channel to allow cells to migrate between wells. Optical glass microscope slides underneath an acrylic plate allow the cultures to be imaged with an inverted microscope. Fluid ports in the acrylic plate are at a level above the 3D cultures to allow introduction of culture media and test agents such as drugs into the wells and the harvesting of media conditioned by the cultures for immunochemical and biochemical analyses. We are using the pathomimetic avatars to identify druggable pathways, screen drug and natural product libraries and accelerate entry of validated drugs or natural products into clinical trials.

  12. Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

    Science.gov (United States)

    de Quervain, Dominique J-F; Margraf, Jürgen

    2008-04-07

    Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of

  13. Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes.

    Science.gov (United States)

    Barnes, Peter J

    2015-09-01

    The recognition that there are some patients with features of asthma and chronic obstructive pulmonary disease (COPD) has highlighted the need to develop more specific treatments for these clinical phenotypes. Some patients with COPD have predominantly eosinophilic inflammation and might respond to high doses of inhaled corticosteroids and newly developed specific antieosinophil therapies, including blocking antibodies against IL-5, IL-13, IL-33, and thymic stromal lymphopoietin, as well as oral chemoattractant receptor-homologous molecule expressed on TH2 cells antagonists. Other patients have severe asthma or are asthmatic patients who smoke with features of COPD-induced inflammation and might benefit from treatments targeting neutrophils, including macrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies against IL-1 and IL-17. Other patients appear to have largely fixed obstruction with little inflammation and might respond to long-acting bronchodilators, including long-acting muscarinic antagonists, to reduce hyperinflation. Highly selected patients with severe asthma might benefit from bronchial thermoplasty. Some patients with overlap syndromes can be conveniently treated with triple fixed-dose combination inhaler therapy with an inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist, several of which are now in development. Corticosteroid resistance is a feature of asthma-COPD overlap syndrome, and understanding the various molecular mechanisms of this resistance has identified novel therapeutic targets and presented the prospect of therapies that can restore corticosteroid responsiveness. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes

    DEFF Research Database (Denmark)

    Deacon, Carolyn F; Holst, Jens J

    2005-01-01

    of appetite. Glucagon-like peptide-1 is, however, extremely rapidly inactivated by the serine peptidase, dipeptidyl peptidase IV, so that the native peptide is not useful clinically. A new approach to utilise the beneficial effects of glucagon-like peptide-1 in the treatment of type 2 diabetes has been...... the development of orally active dipeptidyl peptidase IV inhibitors. Preclinical studies have demonstrated that this approach is effective in enhancing endogenous levels of glucagon-like peptide-1, resulting in improved glucose tolerance in glucose-intolerant and diabetic animal models. In recent studies of 3......-12 months duration in patients with type 2 diabetes, dipeptidyl peptidase IV inhibitors have proved efficacious, both as monotherapy and when given in combination with metformin. Fasting and postprandial glucose concentrations were reduced, leading to reductions in glycosylated haemoglobin levels, while...

  15. Burning mouth syndrome: A review on its diagnostic and therapeutic approach

    Directory of Open Access Journals (Sweden)

    R Aravindhan

    2014-01-01

    Full Text Available Burning mouth syndrome (BMS, a chronic and intractable orofacial pain syndrome is characterized by the presence of burning sensation of the oral mucosa in the absence of specific oral lesion. This condition affects chiefly of middle aged and elderly woman with hormonal changes or psychological disorders. In addition to burning sensation, patient with BMS also complains of oral mucosal pain, altered taste sensation, and dry mouth. This condition is probably of multifactorial origin, often idiopathic and its exact etiopathogenesis remains unclear. So far, there is no definitive cure for this condition and most of the treatment approaches, medications remains unsatisfactory. An interdisciplinary and systematic approach is required for better patient management. The purpose of this article is to present a review of epidemiology, clinical presentation, classification, etiopathogenesis, diagnosis and management of BMS.

  16. Burning mouth syndrome: A review on its diagnostic and therapeutic approach

    Science.gov (United States)

    Aravindhan, R.; Vidyalakshmi, Santhanam; Kumar, Muniapillai Siva; Satheesh, C.; Balasubramanium, A. Murali; Prasad, V. Srinivas

    2014-01-01

    Burning mouth syndrome (BMS), a chronic and intractable orofacial pain syndrome is characterized by the presence of burning sensation of the oral mucosa in the absence of specific oral lesion. This condition affects chiefly of middle aged and elderly woman with hormonal changes or psychological disorders. In addition to burning sensation, patient with BMS also complains of oral mucosal pain, altered taste sensation, and dry mouth. This condition is probably of multifactorial origin, often idiopathic and its exact etiopathogenesis remains unclear. So far, there is no definitive cure for this condition and most of the treatment approaches, medications remains unsatisfactory. An interdisciplinary and systematic approach is required for better patient management. The purpose of this article is to present a review of epidemiology, clinical presentation, classification, etiopathogenesis, diagnosis and management of BMS. PMID:25210377

  17. Current psychological therapeutic approaches for gambling disorder with psychiatric comorbidities: A narrative review

    OpenAIRE

    Echeburúa, Enrique; Amor, Pedro J.; Gómez, Montserrat

    2017-01-01

    Abstract: Background: Although the presence of a gambling disorder (GD) together with another mental disorder poses special treatment challenges, such as relapses, severe outcomes for patients and families, and increased number of hospitalizations, there are only a few critical reviews in the literature. Objective: To review empirical evidence of psychological approaches to cope specifically with these dual disorders. Method: A narrative review of the relevant bibliography on this topic wa...

  18. Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo.

    Science.gov (United States)

    Bardhan, Rizia; Chen, Wenxue; Bartels, Marc; Perez-Torres, Carlos; Botero, Maria F; McAninch, Robin Ward; Contreras, Alejandro; Schiff, Rachel; Pautler, Robia G; Halas, Naomi J; Joshi, Amit

    2010-12-08

    Nanoparticle-based therapeutics with local delivery and external electromagnetic field modulation holds extraordinary promise for soft-tissue cancers such as breast cancer; however, knowledge of the distribution and fate of nanoparticles in vivo is crucial for clinical translation. Here we demonstrate that multiple diagnostic capabilities can be introduced in photothermal therapeutic nanocomplexes by simultaneously enhancing both near-infrared fluorescence and magnetic resonance imaging (MRI). We track nanocomplexes in vivo, examining the influence of HER2 antibody targeting on nanocomplex distribution over 72 h. This approach provides valuable, detailed information regarding the distribution and fate of complex nanoparticles designed for specific diagnostic and therapeutic functions.

  19. New diagnostic and therapeutic approach to thyroid-associated orbitopathy based on applied kinesiology and homeopathic therapy.

    Science.gov (United States)

    Moncayo, Roy; Moncayo, Helga; Ulmer, Hanno; Kainz, Hartmann

    2004-08-01

    To investigate pathogenetic mechanisms related to the lacrimal and lymphatic glands in patients with thyroid-associated orbitopathy (TAO), and the potential of applied kinesiology diagnosis and homeopathic therapeutic measures. Prospective. Thyroid outpatient unit and a specialized center for complementary medicine (WOMED, Innsbruck; R.M. and H.M.). Thirty-two (32) patients with TAO, 23 with a long-standing disease, and 9 showing discrete initial changes. All patients were euthyroid at the time of the investigation. Clinical investigation was done, using applied kinesiology methods. Departing from normal reacting muscles, both target organs as well as therapeutic measures were tested. Affected organs will produce a therapy localization (TL) that turns a normal muscle tone weak. Using the same approach, specific counteracting therapies (i.e., tonsillitis nosode and lymph mobilizing agents) were tested. Change of lid swelling, of ocular movement discomfort, ocular lock, tonsil reactivity and Traditional Chinese Medicine criteria including tenderness of San Yin Jiao (SP6) and tongue diagnosis were recorded in a graded fashion. Positive TL reactions were found in the submandibular tonsillar structures, the pharyngeal tonsils, the San Yin Jiao point, the lacrimal gland, and with the functional ocular lock test. Both Lymphdiaral (Pascoe, Giessen, Germany) and the homeopathic preparation chronic tonsillitis nosode at a C3 potency (Spagyra, Grödig, Austria) counteracted these changes. Both agents were used therapeutically over 3-6 months, after which all relevant parameters showed improvement. Our study demonstrates the involvement of lymphatic structures and flow in the pathogenesis of TAO. The tenderness of the San Yin Jiao point correlates to the above mentioned changes and should be included in the clinical evaluation of these patients.

  20. Novel therapeutic strategy in the management of COPD: a systems medicine approach.

    Science.gov (United States)

    Lococo, Filippo; Cesario, Alfredo; Del Bufalo, Alessandra; Ciarrocchi, Alessia; Prinzi, Giulia; Mina, Marco; Bonassi, Stefano; Russo, Patrizia

    2015-01-01

    Respiratory diseases including chronic-obstructive-pulmonary-disease (COPD) are globally increasing, with COPD predicted to become the third leading cause of global mortality by 2020. COPD is a heterogeneous disease with COPD-patients displaying different phenotypes as a result of a complex interaction between various genetic, environmental and life-style factors. In recent years, several investigations have been performed to better define such interactions, but the identification of the resulting phenotypes is still somewhat difficult, and may lead to inadequate assessment and management of COPD (usually based solely on the severity of airflow limitation parameter FEV1). In this new scenario, the management of COPD has been driven towards an integrative and holistic approach. The degree of complexity requires analyses based on large datasets (also including advanced functional genomic assays) and novel computational biology approaches (essential to extract information relevant for the clinical decision process and for the development of new drugs). Therefore, according to the emerging "systems/network medicine", COPD should be re.-evaluated considering multiple network(s) perturbations such as genetic and environmental changes. Systems Medicine (SM) platforms, in which patients are extensively characterized, offer a basis for a more targeted clinical approach, which is predictive, preventive, personalized and participatory ("P4-medicine"). It clearly emerges that in the next future, new opportunities will become available for clinical research on rare COPD patterns and for the identification of new biomarkers of comorbidity, severity, and progression. Herein, we overview the literature discussing the opportunity coming from the adoption of SMapproaches in COPD management, focusing on proteomics and metabolomics, and emphasizing the identification of disease sub-clusters, to improve the development of more effective therapies.

  1. Pelvic belt effects on sacroiliac joint ligaments: a computational approach to understand therapeutic effects of pelvic belts.

    Science.gov (United States)

    Sichting, Freddy; Rossol, Jerome; Soisson, Odette; Klima, Stefan; Milani, Thomas; Hammer, Niels

    2014-01-01

    The sacroiliac joint is a widely described source of low back pain. Therapeutic approaches to relieve pain include the application of pelvic belts. However, the effects of pelvic belts on sacroiliac joint ligaments as potential pain generators are mostly unknown. The aim of our study was to analyze the influence of pelvic belts on ligament load by means of a computer model. Experimental computer study using a finite element method. A computer model of the human pelvis was created, comprising bones, ligaments, and cartilage. Detailed geometries, material properties of ligaments, and in-vivo pressure distribution patterns of a pelvic belt were implemented. The effects of pelvic belts on ligament strain were computed in the double-leg stance. Pelvic belts increase sacroiliac joint motion around the sagittal axis but decrease motion around the transverse axis. With pelvic belt application, most of the strained sacroiliac joint ligaments were relieved, especially the sacrospinous, sacrotuberous, and the interosseous sacroiliac ligaments. Sacroiliac joint motion and ligament strains were minute. These results agree with validation data from other studies. Assigning homogenous and linear material properties and excluding muscle forces are clear simplifications of the complex reality. Pelvic belts alter sacroiliac joint motion and provide partial relief of ligament strain that is subjectively marked, although minimal in absolute terms. These findings confirm theories that besides being mechanical stabilizers, the sacroiliac joint ligaments are likely involved in neuromuscular feedback mechanisms. The results from our computer model help with unraveling the therapeutic mechanisms of pelvic belts.

  2. Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation

    Directory of Open Access Journals (Sweden)

    Kelly Barbosa Gama

    2018-01-01

    Full Text Available Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs, through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL. PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106, CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.

  3. A simple and valuable approach for measuring customer satisfaction.

    Science.gov (United States)

    Kinney, William C

    2005-08-01

    To determine the financial impact of poor customer satisfaction and the value of information gained from using a 1-question customer-satisfaction survey in a medical setting. A single-question customer-satisfaction survey was collected from customers presenting to an academic otolaryngology head and neck surgery outpatient clinic. The overall response rate was 25%, overall net promoter score was 67.3%, lowest net promoter score occurred on Wednesday and Friday, overall net potential referrals were 872, and potential lost revenue from dissatisfied customers equaled US 2.3 million dollars. A single-question customer-satisfaction survey may help identify areas of customer dissatisfaction that lead to a significant source of lost revenue. The competitive forces in today's health care environment require medical practices to address issues related to customer satisfaction.

  4. Imaging and therapeutic approach of hemangiomas and vascular malformations in the pediatric age group

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, J; Garel, L [Dept. of Medical Imaging, Hopital Sainte-Justine, Montreal, QB (Canada)

    1999-12-01

    Terminology regarding the vascular lesions of the soft tissues remains confusing. A single classification is necessary in order to decide on the proper investigation and the best treatment. At the Workshop on Vascular Anomalies in Rome in June 1996, the membership accepted the Mulliken and Glowacki classification, which differentiates vascular lesions into vascular tumors, including hemangiomas and vascular malformations. At Sainte-Justine, we have set up a multidisciplinary clinic for the discussion of problem patients with vascular anomalies, both in terms of diagnosis and treatment. In this review, we present our experience regarding the classification, the imaging modalities and the treatment of vascular anomalies. In our experience, Doppler ultrasound should be the initial imaging modality for recognizing vascular tumors from vascular malformations. CT scan or magnetic resonance imaging is best to evaluate the extent of the lesions prior to treatment. A multidisciplinary approach is essential to establish a correct diagnosis and define accordingly the appropriate treatment and follow-up. (orig.)

  5. Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

    Directory of Open Access Journals (Sweden)

    Stefano Mazzoleni

    2017-01-01

    Full Text Available A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections, modulate neural activity (noninvasive brain stimulation, and enhance motivation (virtual reality in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.

  6. A novel therapeutic approach for the treatment of central sleep apnea: The remedē{sup ®} system

    Energy Technology Data Exchange (ETDEWEB)

    Germany, Robin, E-mail: rgermany@respicardia.com [University of Oklahoma School of Medicine (United States); Joseph, Susan [Washington University School of Medicine (United States); James, Kristofer [Respicardia, Inc., Hopkins, MN (United States); Kao, Andrew [University of Missouri School of Medicine, Kansas City (United States); St. Luke' s Mid-America Heart Institute, Kansas City, MO (United States)

    2014-06-15

    Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē{sup ®} System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA.

  7. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    Science.gov (United States)

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. A novel therapeutic approach for the treatment of central sleep apnea: The remedē® system

    International Nuclear Information System (INIS)

    Germany, Robin; Joseph, Susan; James, Kristofer; Kao, Andrew

    2014-01-01

    Central sleep apnea (CSA) occurs primarily in cardiovascular patients and is associated with high morbidity and mortality. The disorder often is unrecognized due to the overlap of symptoms with those of the underlying cardiac disease. CSA can be easily diagnosed with a sleep study. Following optimization of all co-morbidities, the therapeutic approach available currently focuses on mask-based therapies which suffer from poor patient adherence. A new therapy, the remedē ® System, has been developed; it utilizes a transvenous, fully implantable system providing phrenic nerve stimulation intended to restore a more normal breathing pattern. The therapy demonstrated promising results based on an initial chronic study and a randomized trial is underway to further evaluate safety and efficacy of this novel system in patients with CSA

  9. Doxycycline hinders phenylalanine fibril assemblies revealing a potential novel therapeutic approach in phenylketonuria.

    Science.gov (United States)

    De Luigi, Ada; Mariani, Alessandro; De Paola, Massimiliano; Re Depaolini, Andrea; Colombo, Laura; Russo, Luca; Rondelli, Valeria; Brocca, Paola; Adler-Abramovich, Lihi; Gazit, Ehud; Del Favero, Elena; Cantù, Laura; Salmona, Mario

    2015-10-29

    A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloid-like assemblies in the brains of transgenic mouse models and patients with phenylketonuria, possibly shedding light on the selective cognitive deficit associated with this disease. Paralleling the amyloidogenic route that identifies different stages of peptide aggregation, corresponding to different levels of toxicity, we experimentally address for the first time, the physico-chemical properties of phenylalanine aggregates via Small Angle, Wide Angle X-ray Scattering and Atomic Force Microscopy. Results are consistent with the presence of well-structured, aligned fibres generated by milliMolar concentrations of phenylalanine. Moreover, the amyloid-modulating doxycycline agent affects the local structure of phenylalanine aggregates, preventing the formation of well-ordered crystalline structures. Phenylalanine assemblies prove toxic in vitro to immortalized cell lines and primary neuronal cells. Furthermore, these assemblies also cause dendritic sprouting alterations and synaptic protein impairment in neurons. Doxycycline counteracts these toxic effects, suggesting an approach for the development of future innovative non-dietary preventive therapies.

  10. The blood-brain barrier: structure, function and therapeutic approaches to cross it.

    Science.gov (United States)

    Tajes, Marta; Ramos-Fernández, Eva; Weng-Jiang, Xian; Bosch-Morató, Mònica; Guivernau, Biuse; Eraso-Pichot, Abel; Salvador, Bertrán; Fernàndez-Busquets, Xavier; Roquer, Jaume; Muñoz, Francisco J

    2014-08-01

    The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.

  11. An Unusual Endovascular Therapeutic Approach for a Rare Case of May-Thurner Syndrome.

    Science.gov (United States)

    DaSilva-DeAbreu, Adrian; Masha, Luke; Peerbhai, Shareez

    2017-03-06

    BACKGROUND The etiology of deep venous thrombosis (DVT) may pose a significant diagnostic challenge because truly reversible causes of DVT are rare. In this regard, known pelvic anatomic abnormalities such as aortic and iliac aneurysms should be seriously considered as a complicating factor in patients presenting with acute DVT so as not to miss a potentially curable etiology of May-Thurner syndrome (MTS). CASE REPORT We report the case of a 69-year-old man with a known abdominal aortic aneurysm and bilateral iliac artery aneurysms who presented with an acute DVT. A computed tomography scan of the abdomen and pelvis showed increased dilation of his aneurysmal disease with new resultant compression of the left iliac vein representing acquired MTS. The patient underwent endovascular aneurysm repair of the infra-renal abdominal aortic aneurysm and right common iliac artery aneurysm with a Gore Excluder endoprosthesis in lieu of venous stenting, with resolution of symptoms. CONCLUSIONS Infra-renal aortic and iliac aneurysms causing MTS are extremely rare, and patients at risk for MTS through these mechanisms do not fit the classical demographics associated with this syndrome. Furthermore, this is the first case described in which MTS was treated by addressing the aneurysm through an endoprosthetic approach instead of venous stenting, which is the conventional intervention for MTS.

  12. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches.

    Science.gov (United States)

    Belizário, José E; Napolitano, Mauro

    2015-01-01

    The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.

  13. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

    Science.gov (United States)

    Masson, Patrick

    2011-09-25

    After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Type 2 diabetes: epidemiologic trends, evolving pathogenetic [corrected] concepts, and recent changes in therapeutic approach.

    Science.gov (United States)

    Rizvi, Ali A

    2004-11-01

    The prevalence of type 2 diabetes has assumed epidemic dimensions. Children are now vulnerable to a disease that was once the exclusive domain of adulthood. Increased body weight and sedentary behavior accelerate insulin resistance and beta-cell dysfunction, leading to the clinical manifestation of hyperglycemia. Other cardiovascular risk factors tend to cluster in this milieu, setting the stage for vastly increased macrovascular morbidity. Many more people have impaired glucose tolerance ('prediabetes'). They are not only at risk for frank diabetes but also for the recently recognized entity of 'metabolic syndrome,' which is further characterized by hypertension, dyslipidemia, and central adiposity. A multifactorial approach addressing these aspects in addition to intensive glycemic control is the most efficacious therapy, optimally achieved through a team effort comprising the clinician, diabetes nurse, dietitian, and other professionals. Early use of oral-agent combinations is gaining favor. Insulin is best utilized in a basal-bolus fashion to manage both fasting and postprandial glycemia, delivered with multiple-dose injections or continuously via the pump. In hospitalized patients, good diabetic control reduces mortality. Finally, recent trials show that optimal weight maintenance and regular exercise can prevent or delay type 2 diabetes. Such information can serve as the foundation for large-scale preventive endeavors at the community level.

  15. HUMAN MICROBIOMES AND THEIR ROLES IN DYSBIOSIS, COMMON DISEASES AND NOVEL THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Jose Ernesto Belizario

    2015-10-01

    Full Text Available The human body is the residence of a large number of commensal (non-pathogenic and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics as well as phages engineered with CRISPR/cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community and common diseases (e.g. diabetes and obesity. The designing and production of pharmaceuticals based on our own body’s microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.

  16. Prevention and treatment of allergic asthma in pregnancy: from conventional drugs to new therapeutical approaches.

    Science.gov (United States)

    Cadavid, Angela P; Bannenberg, Gérard L; Arck, Petra C; Fitzgerald, Justine S; Markert, Udo R

    2011-05-01

    Different conventional anti-asthmatic and anti-allergic drugs are commonly used in pregnancy, including inhaled corticosteroids, long- and short-acting β-agonists, leukotriene modifiers, cromolyn, and theophylline. Alternatively, immunotherapy with allergens before and during pregnancy is accepted as a causal treatment of allergies, but the allergy specifity and severity in combination with a variety of application protocols and procedures cause wide heterogenity of this treatment principle. Furthermore, the pharmacokinetic characteristics and the US Food and Drug Administration (FDA) classification of conventional anti-allergic drugs and immunological implications of immunotherapy are summarized in this review, and insights on fetal programming of allergies are introduced. We propose a potential perspective of treatment with anti-inflammatory and pro-resolving mediators, such as lipoxins, resolvins and protectins; these are lipid mediators physiologically generated during the immune response from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. This proposal fits with the recently appreciated approaches to allergy prevention for the newborn child by a balanced maternal nutrition and omega-3 long-chain polyunsaturated fatty acid consumption.

  17. Recovery and utilization of valuable metals from spent nuclear fuel. 3: Mutual separation of valuable metals

    International Nuclear Information System (INIS)

    Kirishima, K.; Shibayama, H.; Nakahira, H.; Shimauchi, H.; Myochin, M.; Wada, Y.; Kawase, K.; Kishimoto, Y.

    1993-01-01

    In the project ''Recovery and Utilization of Valuable Metals from Spent Fuel,'' mutual separation process of valuable metals recovered from spent fuel has been studied by using the simulated solution contained Pb, Ru, Rh, Pd and Mo. Pd was separated successfully by DHS (di-hexyl sulfide) solvent extraction method, while Pb was recovered selectively from the raffinate by neutralization precipitation of other elements. On the other hand, Rh was roughly separated by washing the precipitate with alkaline solution, so that Rh was refined by chelate resin CS-346. Outline of the mutual separation process flow sheet has been established of the combination of these techniques. The experimental results and the process flow sheet of mutual separation of valuable metals are presented in this paper

  18. Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm.

    Science.gov (United States)

    Philippe, Laure; Ceroi, Adam; Bôle-Richard, Elodie; Jenvrin, Alizée; Biichle, Sabeha; Perrin, Sophie; Limat, Samuel; Bonnefoy, Francis; Deconinck, Eric; Saas, Philippe; Garnache-Ottou, Francine; Angelot-Delettre, Fanny

    2017-11-01

    Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematologic malignancy with a poor prognosis. No consensus regarding optimal treatment modalities is currently available. Targeting the nuclear factor-kappa B pathway is considered a promising approach since blastic plasmacytoid dendritic cell neoplasm has been reported to exhibit constitutive activation of this pathway. Moreover, nuclear factor-kappa B inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines, achieved using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib, interferes in vitro with leukemic cell proliferation and survival. Here we extended these data by showing that primary blastic plasmacytoid dendritic cell neoplasm cells from seven patients were sensitive to bortezomib-induced cell death. We confirmed that bortezomib efficiently inhibits the phosphorylation of the RelA nuclear factor-kappa B subunit in blastic plasmacytoid dendritic cell neoplasm cell lines and primary cells from patients in vitro and in vivo in a mouse model. We then demonstrated that bortezomib can be associated with other drugs used in different chemotherapy regimens to improve its impact on leukemic cell death. Indeed, when primary blastic plasmacytoid dendritic cell neoplasm cells from a patient were grafted into mice, bortezomib treatment significantly increased the animals' survival, and was associated with a significant decrease of circulating leukemic cells and RelA nuclear factor-kappa B subunit expression. Overall, our results provide a rationale for the use of bortezomib in combination with other chemotherapy for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm. Based on our data, a prospective clinical trial combining proteasome inhibitor with classical drugs could be envisaged. Copyright© Ferrata Storti Foundation.

  19. Recovering valuable metals from recycled photovoltaic modules.

    Science.gov (United States)

    Yi, Youn Kyu; Kim, Hyun Soo; Tran, Tam; Hong, Sung Kil; Kim, Myong Jun

    2014-07-01

    Recovering valuable metals such as Si, Ag, Cu, and Al has become a pressing issue as end-of-life photovoltaic modules need to be recycled in the near future to meet legislative requirements in most countries. Of major interest is the recovery and recycling of high-purity silicon (> 99.9%) for the production of wafers and semiconductors. The value of Si in crystalline-type photovoltaic modules is estimated to be -$95/kW at the 2012 metal price. At the current installed capacity of 30 GW/yr, the metal value in the PV modules represents valuable resources that should be recovered in the future. The recycling of end-of-life photovoltaic modules would supply > 88,000 and 207,000 tpa Si by 2040 and 2050, respectively. This represents more than 50% of the required Si for module fabrication. Experimental testwork on crystalline Si modules could recover a > 99.98%-grade Si product by HNO3/NaOH leaching to remove Al, Ag, and Ti and other metal ions from the doped Si. A further pyrometallurgical smelting at 1520 degrees C using CaO-CaF2-SiO2 slag mixture to scavenge the residual metals after acid leaching could finally produce > 99.998%-grade Si. A process based on HNO3/NaOH leaching and subsequent smelting is proposed for recycling Si from rejected or recycled photovoltaic modules. Implications: The photovoltaic industry is considering options of recycling PV modules to recover metals such as Si, Ag, Cu, Al, and others used in the manufacturing of the PV cells. This is to retain its "green" image and to comply with current legislations in several countries. An evaluation of potential resources made available from PV wastes and the technologies used for processing these materials is therefore of significant importance to the industry. Of interest are the costs of processing and the potential revenues gained from recycling, which should determine the viability of economic recycling of PV modules in the future.

  20. PICKLED PUMPKIN IS VALUABLE FOOD PRODUCT

    Directory of Open Access Journals (Sweden)

    T. A. Sannikova

    2017-01-01

    Full Text Available One of the main directions of the food industry development is the production of functional food products. Changes in the human’s diet structure cause that none of population group does receive necessary amount of vitamins, macro and microelements in healthy routine diet. To solve this problem, food stuffs enhanced by different ingredients enable to improve the biological and food value. The pumpkin is a valuable source of such important substances as carotene and pectin. Addition of garlic and hot pepper ingredients to process of pumpkin pickling enables to enrich the products with carbohydrates, proteins, microelements, which have low or no content in the pumpkin fruit. Therefore, the study of the influence of the different quantities of garlic and hot pepper additions on chemical composition of finished product is very important. The influence of plant additions used on chemical composition of finished product had been well determined. It was shown that through increased doses of garlic and hot pepper ingredients as compared with control, the carotene and dry matter content then decreased by 1.16%-3.43% in pickled pumpkin, while the pectin content depended on added component. The highest pectin content, 0.71% was observed at addition of 10 g. garlic ingredient per 1 kg. of raw matter, that was 4.1 times higher than control. With increased addition of hot pepper ingredient the pectin accumulation was decreasing from 0.58% in control to 0.36% in variant 10g. per 1kg. of raw matter.

  1. Valuable metals - recovery processes, current trends, and recycling strategies

    Energy Technology Data Exchange (ETDEWEB)

    Froehlich, Peter; Lorenz, Tom; Martin, Gunther; Brett, Beate; Bertau, Martin [Institut fuer Technische Chemie, TU Bergakademie Freiberg, Leipziger Strasse 29, 09599, Freiberg (Germany)

    2017-03-01

    This Review provides an overview of valuable metals, the supply of which has been classified as critical for Europe. Starting with a description of the current state of the art, novel approaches for their recovery from primary resources are presented as well as recycling processes. The focus lies on developments since 2005. Chemistry strategies which are used in metal recovery are summarized on the basis of the individual types of deposit and mineral. In addition, the economic importance as well as utilization of the metals is outlined. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach.

    Science.gov (United States)

    Duffau, Hugues; Taillandier, Luc

    2015-03-01

    Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. [Common physiological basis for post-traumatic stress disorder and dependence to drugs of abuse: Implications for new therapeutic approaches].

    Science.gov (United States)

    Gisquet-Verrier, Pascale; Tolédano, Daniel; Le Dorze, Claire

    2017-06-01

    Post-traumatic stress disorder (PTSD) and addiction to drugs of abuse are two common diseases, showing high comorbidity rates. This review presents a number of evidence showing similarities between these two pathologies, especially the hyper-responsiveness to environmental cues inducing a reactivation of the target memory leading either to re-experiencing (PTSD), or drug craving. Accordingly, PTSD and addiction to drug of abuse might by considered as memory pathologies, underlined by the same physiological process. We propose that these two pathologies rely on an uncoupling of the monoaminergic systems. According to this hypothesis, exposure to extreme conditions, either negative (trauma) or positive (drugs) induced a loss of the reciprocal control that one system usually exerts on the other monoaminergic system, resulting to an uncoupling between the noradrenergic and the serotonergic systems. Results obtained in our laboratory, using animal models of these pathologies, demonstrate that after a trauma, such as after repeated drug injections, rats developed both a behavioral sensitization (increases of the locomotion in response to a stimulation of the monoaminergic systems) and a pharmacological sensitization (increases of noradrenergic release within the prefrontal cortex). These results support our hypothesis and led us to propose new and innovative therapeutic approaches consisting either to induce a re-coupling of the monoaminergic systems, or to modify the pathological memories by using an emotional memory remodeling. Extremely encouraging results have already been obtained in rats and in humans, opening new and promising therapeutic avenues. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  4. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin

    Directory of Open Access Journals (Sweden)

    Seufert J

    2015-11-01

    Full Text Available Jochen SeufertDepartment of Endocrinology and Diabetology, Clinic for Internal Medicine II, Freiburg University Hospital, Freiburg, GermanyAbstract: Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2 inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These "concomitant effects" are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand

  5. Obesity, Metabolic Syndrome, and Dietary Therapeutical Approaches with a Special Focus on Nutraceuticals (Polyphenols): A Mini-Review.

    Science.gov (United States)

    Ríos-Hoyo, Alejandro; Cortés, María José; Ríos-Ontiveros, Huguette; Meaney, Eduardo; Ceballos, Guillermo; Gutiérrez-Salmeán, Gabriela

    2014-01-01

    More than half of all global deaths in 2010 were related to non-communicable diseases, including obesity, cancers, diabetes, and cardiovascular illnesses. It has been suggested that the alarming increase in the incidence of cardiovascular disease is the epidemiologic result of a nutrition transition characterized by dietary patterns featuring an increase in the intake of total fat, cholesterol, sugars, and other refined carbohydrates, concomitant with low consumption of polyunsaturated fatty acids and fiber. Although traditional dietary approaches have proven successful as part of the treatment for obesity and cardiometabolic derangements within clinical trial scenarios, they lack effectiveness in the long term, mainly due to poor compliance. Research has thus turned its attention to nutraceutics, nutrients that have the ability to modulate physiological and pathophysiological molecular mechanisms, thus resulting in favorable health outcomes. Polyphenols have been considered as among the bioactive molecules as they are thought to yield beneficial effects by exerting antioxidant activity; however, there are other--and even more robust--metabolic pathways through which polyphenols enhance cardiovascular health, such as via promoting vasodilatory, anti-atherogenic, antithrombotic, and anti-inflammatory effects. No standard dose has yet been determined, as the effects greatly vary among polyphenols and food sources; thus, there is an imperative need to generate more evidence in order to support dietary recommendations aimed at the prevention and therapeutics of obesity and its associated cardiometabolic diseases.

  6. The Impact of CRISPR/Cas9 Technology on Cardiac Research: From Disease Modelling to Therapeutic Approaches

    Science.gov (United States)

    Pramstaller, Peter P.; Hicks, Andrew A.; Rossini, Alessandra

    2017-01-01

    Genome-editing technology has emerged as a powerful method that enables the generation of genetically modified cells and organisms necessary to elucidate gene function and mechanisms of human diseases. The clustered regularly interspaced short palindromic repeats- (CRISPR-) associated 9 (Cas9) system has rapidly become one of the most popular approaches for genome editing in basic biomedical research over recent years because of its simplicity and adaptability. CRISPR/Cas9 genome editing has been used to correct DNA mutations ranging from a single base pair to large deletions in both in vitro and in vivo model systems. CRISPR/Cas9 has been used to increase the understanding of many aspects of cardiovascular disorders, including lipid metabolism, electrophysiology and genetic inheritance. The CRISPR/Cas9 technology has been proven to be effective in creating gene knockout (KO) or knockin in human cells and is particularly useful for editing induced pluripotent stem cells (iPSCs). Despite these progresses, some biological, technical, and ethical issues are limiting the therapeutic potential of genome editing in cardiovascular diseases. This review will focus on various applications of CRISPR/Cas9 genome editing in the cardiovascular field, for both disease research and the prospect of in vivo genome-editing therapies in the future. PMID:29434642

  7. Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

    International Nuclear Information System (INIS)

    Salo, Tuula; Vered, Marilena; Bello, Ibrahim O.; Nyberg, Pia; Bitu, Carolina Cavalcante; Zlotogorski Hurvitz, Ayelet; Dayan, Dan

    2014-01-01

    The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed. - Highlights: • Tumor depth and budding, hypoxia and TME cells associate with worse prognosis. • Pro-tumoral CAFs and CAI cells aid proliferation, invasion and spread hypoxia. • Some ECM-bound factors exert pro-angiogenic or pro-tumor activities. • Tumor spread is greatly dependent on ECM proteolysis, mediated by TME cells. • Direct targeting of TME components for treatment is still experimental

  8. Intermittent hypoxia initiated plasticity in humans: A multipronged therapeutic approach to treat sleep apnea and overlapping co-morbidities.

    Science.gov (United States)

    Mateika, Jason H; Komnenov, Dragana

    2017-01-01

    Over the past three decades exposure to intermittent hypoxia (IH) has generally been considered a stimulus associated with a number of detrimental outcomes. However, there is sufficient evidence to link IH to many beneficial outcomes but they have largely been ignored, particularly in the field of sleep medicine in the United States. Recent reviews have postulated that this apparent contradiction is related to the severity and duration of exposure to IH; mild forms of IH initiate beneficial outcomes while severe forms of IH are coupled to detrimental consequences. In the present review we explore the role that IH has in initiating respiratory plasticity and the potential this form of plasticity has to mitigate obstructive sleep apnea (OSA) in humans. In taking this approach, we address the possibility that IH could serve as an adjunct therapy coupled with continuous positive airway pressure (CPAP) to treat OSA. Our working hypothesis is that exposure to mild IH leads to respiratory plasticity that manifests in increased stability of the upper airway, which could ultimately reduce the CPAP required to treat OSA. In turn, this reduction could increase CPAP compliance and extend the length of treatment each night, which might improve the magnitude of outcome measures. Improved treatment compliance coupled with the direct effect that IH has on numerous overlapping conditions (i.e. asthma, chronic obstructive pulmonary disease, spinal cord injury) may well lead to substantial improvements that exceed outcomes following treatment with CPAP alone. Overall, this review will consider evidence from the published literature which suggests that IH could serve as an effective multipronged therapeutic approach to treat sleep apnea and its overlapping co-morbidities. Published by Elsevier Inc.

  9. Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

    Energy Technology Data Exchange (ETDEWEB)

    Salo, Tuula, E-mail: Tuula.salo@oulu.fi [Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu (Finland); Oulu University Central Hospital, Oulu (Finland); Institute of Dentistry, University of Helsinki, Helsinki (Finland); Vered, Marilena [Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan (Israel); Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel); Bello, Ibrahim O. [Department of Oral Medicine and Diagnostic Sciences, King Saud University, Riyadh (Saudi Arabia); Nyberg, Pia [Oulu University Central Hospital, Oulu (Finland); Bitu, Carolina Cavalcante [Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu (Finland); Zlotogorski Hurvitz, Ayelet [Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel); Department of Oral and Maxillofacial Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva (Israel); Dayan, Dan [Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel)

    2014-07-15

    The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed. - Highlights: • Tumor depth and budding, hypoxia and TME cells associate with worse prognosis. • Pro-tumoral CAFs and CAI cells aid proliferation, invasion and spread hypoxia. • Some ECM-bound factors exert pro-angiogenic or pro-tumor activities. • Tumor spread is greatly dependent on ECM proteolysis, mediated by TME cells. • Direct targeting of TME components for treatment is still experimental.

  10. Insomnio: enfoque diagnóstico y terapéutico Diagnostic and therapeutic approach to insomnia

    Directory of Open Access Journals (Sweden)

    Johanna Diago García

    2005-01-01

    Full Text Available El sueño excesivo, insuficiente o desbalanceado disminuye la calidad de vida y afecta el funcionamiento biopsicosocial de la persona. Entre 20 y 50% de los adultos refieren una alteración en su dormir, y esta frecuencia aumenta con la edad. El insomnio es la queja más común en la población general y en los pacientes psiquiátricos; de ahí la importancia de enfocar adecuadamente, desde los puntos de vista diagnóstico y terapéutico, este problema de salud. El insomnio es un síntoma y se deben corregir primero sus causas; el estudio debe incluir el diario del sueño y la información de un testigo del dormir del paciente. El tratamiento varía según el tipo de insomnio y su etiología; las medidas generales pueden o no ser de tipo farmacológico e incluyen: higiene del sueño, intervenciones cognitivo-conductuales, restricción del sueño, técnicas de relajación y administración de medicamentos. En general se acepta que cuando el insomnio lleva menos de tres semanas de evolución no requiere ninguna intervención excepto las medidas sobre higiene del sueño; si esto no es suficiente, se perpetúa en el tiempo o se identifican otras causas, se deberá hacer un manejo de tipo específico. Excessive, insufficient or unbalanced sleep reduces life quality and severely affects the biopsychosocial functioning of the person. Between 20 and 50% of adults suffer from sleep disturbances and their frequency increases withaging. Insomnia is the most common complaint in the general population and in psychiatric patients; therefore, it is important to have an adequate diagnostic and therapeutic approach in order to be able to solve the problem. Insomnia is just a symptom and its causes must be solved in the first place; the diagnostic study must include a sleep diary and the information provided by relatives. Treatment varies depending on the kind of insomnia and its etiology; general measures can be pharmacological or non-pharmacological; they

  11. Sol-gel derived manganese-releasing bioactive glass as a therapeutical approach for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Barrioni, B.R.; Oliveira, A.C.; Leite, M.F.; Pereira, M.M. [Universidade Federal de Minas Gerais (UFMG), MG (Brazil)

    2016-07-01

    Full text: Bioactive glasses (BG) have been highlighted in tissue engineering, due to their high bioactivity and biocompatibility, being potential materials for bone tissue repair. Its composition is variable and quite flexible, allowing the incorporation of therapeutic metallic ions, which has been regarded as a promising approach in the development of BG with superior properties for tissue engineering. These ions can be released in a controlled manner during the dissolution process of the glass, having the advantage of being released at the exactly implant site where they are needed, thus optimizing the therapeutic efficacy and reducing undesired side effects in the patient. Among several ions that have been studied, Manganese (Mn) has been shown to favor osteogenic differentiation. Besides, this ion is also a cofactor for several enzymes involved in remodeling of extracellular matrix, presenting an important role in cell adhesion. Therefore, it is very important to study the Mn role in the BG network and its influence on the glass bioactivity. In this context, new bioactive glass compositions derived from the 58S (60%SiO2-36%CaO-4%P2O5, mol%) were synthesized in this work, using the sol-gel method, by the incorporation of Mn into their structure. FTIR and Raman spectra showed the presence of typical BG chemical groups, whereas the amorphous structure typical of these materials was confirmed by XRD analysis, which also indicated that the Mn incorporation in the glass network was well succeeded, as its precursor did not recrystallize. The role of Mn in the glass network was also evaluated by XPS. The influence of Mn on carbonated hydroxyapatite layer formation after different periods of immersion of the BG powder in Simulated Body Fluid was evaluated using zeta potential, SEM, EDS and FTIR, whereas the controlled ion release was measured through ICP-OES. MTT assay revealed that Mn-containing BG showed no cytotoxic effect on cell culture. All these results indicate

  12. Sol-gel derived manganese-releasing bioactive glass as a therapeutical approach for bone tissue engineering

    International Nuclear Information System (INIS)

    Barrioni, B.R.; Oliveira, A.C.; Leite, M.F.; Pereira, M.M.

    2016-01-01

    Full text: Bioactive glasses (BG) have been highlighted in tissue engineering, due to their high bioactivity and biocompatibility, being potential materials for bone tissue repair. Its composition is variable and quite flexible, allowing the incorporation of therapeutic metallic ions, which has been regarded as a promising approach in the development of BG with superior properties for tissue engineering. These ions can be released in a controlled manner during the dissolution process of the glass, having the advantage of being released at the exactly implant site where they are needed, thus optimizing the therapeutic efficacy and reducing undesired side effects in the patient. Among several ions that have been studied, Manganese (Mn) has been shown to favor osteogenic differentiation. Besides, this ion is also a cofactor for several enzymes involved in remodeling of extracellular matrix, presenting an important role in cell adhesion. Therefore, it is very important to study the Mn role in the BG network and its influence on the glass bioactivity. In this context, new bioactive glass compositions derived from the 58S (60%SiO2-36%CaO-4%P2O5, mol%) were synthesized in this work, using the sol-gel method, by the incorporation of Mn into their structure. FTIR and Raman spectra showed the presence of typical BG chemical groups, whereas the amorphous structure typical of these materials was confirmed by XRD analysis, which also indicated that the Mn incorporation in the glass network was well succeeded, as its precursor did not recrystallize. The role of Mn in the glass network was also evaluated by XPS. The influence of Mn on carbonated hydroxyapatite layer formation after different periods of immersion of the BG powder in Simulated Body Fluid was evaluated using zeta potential, SEM, EDS and FTIR, whereas the controlled ion release was measured through ICP-OES. MTT assay revealed that Mn-containing BG showed no cytotoxic effect on cell culture. All these results indicate

  13. Global habitat preferences of commercially valuable tuna

    KAUST Repository

    Arrizabalaga, Haritz; Dufour, Florence; Kell, Laurence T.; Merino, Gorka; Ibaibarriaga, Leire; Chust, Guillem; Irigoien, Xabier; Santiago, Josu; Murua, Hilario; Fraile, Igaratza; Chifflet, Marina; Goikoetxea, Nerea; Sagarminaga, Yolanda; Aumont, Olivier; Bopp, Laurent; Herrera, Miguel Angel; Marc Fromentin, Jean; Bonhomeau, Sylvain

    2015-01-01

    In spite of its pivotal role in future implementations of the Ecosystem Approach to Fisheries Management, current knowledge about tuna habitat preferences remains fragmented and heterogeneous, because it relies mainly on regional or local studies that have used a variety of approaches making them difficult to combine. Therefore in this study we analyse data from six tuna species in the Pacific, Atlantic and Indian Oceans in order to provide a global, comparative perspective of habitat preferences. These data are longline catch per unit effort from 1958 to 2007 for albacore, Atlantic bluefin, southern bluefin, bigeye, yellowfin and skipjack tunas. Both quotient analysis and Generalised Additive Models were used to determine habitat preference with respect to eight biotic and abiotic variables. Results confirmed that, compared to temperate tunas, tropical tunas prefer warm, anoxic, stratified waters. Atlantic and southern bluefin tuna prefer higher concentrations of chlorophyll than the rest. The two species also tolerate most extreme sea surface height anomalies and highest mixed layer depths. In general, Atlantic bluefin tuna tolerates the widest range of environmental conditions. An assessment of the most important variables determining fish habitat is also provided. © 2014 Elsevier Ltd.

  14. Global habitat preferences of commercially valuable tuna

    KAUST Repository

    Arrizabalaga, Haritz

    2015-03-01

    In spite of its pivotal role in future implementations of the Ecosystem Approach to Fisheries Management, current knowledge about tuna habitat preferences remains fragmented and heterogeneous, because it relies mainly on regional or local studies that have used a variety of approaches making them difficult to combine. Therefore in this study we analyse data from six tuna species in the Pacific, Atlantic and Indian Oceans in order to provide a global, comparative perspective of habitat preferences. These data are longline catch per unit effort from 1958 to 2007 for albacore, Atlantic bluefin, southern bluefin, bigeye, yellowfin and skipjack tunas. Both quotient analysis and Generalised Additive Models were used to determine habitat preference with respect to eight biotic and abiotic variables. Results confirmed that, compared to temperate tunas, tropical tunas prefer warm, anoxic, stratified waters. Atlantic and southern bluefin tuna prefer higher concentrations of chlorophyll than the rest. The two species also tolerate most extreme sea surface height anomalies and highest mixed layer depths. In general, Atlantic bluefin tuna tolerates the widest range of environmental conditions. An assessment of the most important variables determining fish habitat is also provided. © 2014 Elsevier Ltd.

  15. Dual Targeting of Amyloid-beta Clearance and Neuroinflammation as a Novel Therapeutic Approach against Alzheimer's Disease

    Science.gov (United States)

    Batarseh, Yazan S.

    Amyloid-beta (Abeta) cascade hypothesis suggests that Alzheimer's disease (AD) is related to an imbalance between the production and clearance of Abeta peptide. Sporadic AD has been related to faulty clearance of Abeta. Accumulation of Abeta oligomers (Abetao) has been linked to several downstream toxic effects including neuroinflammation, synaptic loss, and cellular death. Abeta transport across the blood-brain barrier (BBB) is one of the primary pathways for reducing Abeta load in the brain, which work hand in hand with other parenchymal mechanisms to reduce Abeta levels including intra and extracellular degradation by a family of Abeta degrading enzymes. Established AD drugs, such as the cholinesterase inhibitor donepezil, have been reported to have several additional non-cholinergic effects that alter Abeta pathology; reduce Abeta load, anti-inflammatory response, and attenuate synaptic loss. However, their limited effect only lead to minor improvements in AD symptoms without improving the prognosis of the disease. The lack of effective medical treatment for AD led to several studies focusing on establishing new therapeutic approaches to reduce Abeta pathology. We aimed to identify and characterize natural products that are capable of enhancing the BBB clearance of Abeta in addition to reducing neuroinflammation. Our first project was to investigate the role of oleocanthal (one of the active ingredients in extra-virgin olive oil; EVOO) on attenuating Abeta toxic effects on neurons and astrocytes. We developed Abeta oligomers (Abetao) induced inflammatory environment by exposing neurons and astrocytes to accumulative doses of Abetao to investigate oleocanthal effect on modulating Abetao pathological changes in neurons and astrocytes. Our findings demonstrated oleocanthal prevented Abetao-induced synaptic proteins, SNAP-25 and PSD-95, down-regulation in neurons, attenuated Abetao-induced inflammation, and restored glutamine transporter (GLT1) and glucose

  16. How valuable is word of mouth?

    Science.gov (United States)

    Kumar, V; Petersen, J Andrew; Leone, Robert P

    2007-10-01

    The customers who buy the most from you are probably not your best marketers. What's more, your best marketers may be worth far more to your company than your most enthusiastic consumers. Those are the conclusions of professors Kumar and Petersen at the University of Connecticut and professor Leone at Ohio State University, who analyzed thousands of customers in research focused on a telecommunications company and a financial services firm. In this article, the authors present a straightforward tool that can be used to calculate both customer lifetime value (CLV), the worth of your customers' purchases, and customer referral value (CRV), the value of their referrals. Knowing both enables you to segment your customers into four constituent parts: those that buy a lot but are poor marketers (which they term Affluents); those that don't buy much but are very strong salespeople for your firm (Advocates); those that do both well (Champions); and those that do neither well (Misers). In a series of one-year experiments, the authors demonstrated the effectiveness of this segmentation approach. Offering purchasing incentives to Advocates, referral incentives to Affluents, and both to Misers, they were able to move significant proportions of all three into the Champions category. Both companies reaped returns on their marketing investments greater than 12-fold--more than double the normal marketing ROI for their industries. The power of this tool is its ability to help marketers decide where to focus their efforts. Rather than waste funds encouraging big spenders to spend slightly more while overlooking the power of customer evangelists who don't buy enough to seem important, you can reap much higher rewards by nudging big spenders to make referrals and urging enthusiastic proponents of your wares to buy a bit more.

  17. Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

    Science.gov (United States)

    Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

    2016-06-02

    To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under

  18. The Therapeutic Approach to a Patient's Criminal Offense in a Forensic Mental Health Nurse-Patient Relationship-The Nurses' Perspectives.

    Science.gov (United States)

    Askola, Riitta; Nikkonen, Merja; Putkonen, Hanna; Kylmä, Jari; Louheranta, Olavi

    2017-07-01

    The purpose of this study is to describe the therapeutic approach to a patient's criminal offense in a forensic mental health nurse-patient relationship from the nurse's perspective. Eight nurses in a Finnish forensic psychiatric hospital were interviewed, and the resultant research material was analyzed by inductive content analysis. The results revealed the process of the therapeutic approach to a patient's offense, which comprises numerous steps and various phases. For the nurse, the process of working through the offense can be divided into stages in which an attempt is made to respond to the patient's behavior and interaction in a manner that leads to working through the criminal act. © 2016 Wiley Periodicals, Inc.

  19. Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

    Science.gov (United States)

    2011-02-01

    Therapeutic and Imaging Agents to Lung Cancer (PI and co-PI: Renata Pasqualini , Ph.D., Wadih Arap, M.D., Ph.D.) The studies outlined in this proposal...with Drs. Pasqualini , Arap, and Wistuba. The IHC staining of lung cancer TMAs (390 cases) has been completed. We are working with investigators to...Project 3, R. Pasqualini ). This project was completed and a manuscript is in preparation by Dr. Pasqualini’s lab. b) Molecular abnormalities

  20. Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus

    Directory of Open Access Journals (Sweden)

    Lilian S.R. Sadeck

    2014-11-01

    Conclusion: The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks.

  1. Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival

    Directory of Open Access Journals (Sweden)

    Schultz Chad R

    2012-04-01

    Full Text Available Abstract Background The current treatment regimen for glioma patients is surgery, followed by radiation therapy plus temozolomide (TMZ, followed by 6 months of adjuvant TMZ. Despite this aggressive treatment regimen, the overall survival of all surgically treated GBM patients remains dismal, and additional or different therapies are required. Depending on the cancer type, SPARC has been proposed both as a therapeutic target and as a therapeutic agent. In glioma, SPARC promotes invasion via upregulation of the p38 MAPK/MAPKAPK2/HSP27 signaling pathway, and promotes tumor cell survival by upregulating pAKT. As HSP27 and AKT interact to regulate the activity of each other, we determined whether inhibition of HSP27 was better than targeting SPARC as a therapeutic approach to inhibit both SPARC-induced glioma cell invasion and survival. Results Our studies found the following. 1 SPARC increases the expression of tumor cell pro-survival and pro-death protein signaling in balance, and, as a net result, tumor cell survival remains unchanged. 2 Suppressing SPARC increases tumor cell survival, indicating it is not a good therapeutic target. 3 Suppressing HSP27 decreases tumor cell survival in all gliomas, but is more effective in SPARC-expressing tumor cells due to the removal of HSP27 inhibition of SPARC-induced pro-apoptotic signaling. 4 Suppressing total AKT1/2 paradoxically enhanced tumor cell survival, indicating that AKT1 or 2 are poor therapeutic targets. 5 However, inhibiting pAKT suppresses tumor cell survival. 6 Inhibiting both HSP27 and pAKT synergistically decreases tumor cell survival. 7 There appears to be a complex feedback system between SPARC, HSP27, and AKT. 8 This interaction is likely influenced by PTEN status. With respect to chemosensitization, we found the following. 1 SPARC enhances pro-apoptotic signaling in cells exposed to TMZ. 2 Despite this enhanced signaling, SPARC protects cells against TMZ. 3 This protection can be reduced

  2. Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.

    Science.gov (United States)

    Basson, Abigail R; Lam, Minh; Cominelli, Fabio

    2017-12-01

    The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  4. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  5. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  6. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  7. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2015-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  8. New Therapies Offer Valuable Options for Patients with Melanoma

    Science.gov (United States)

    Two phase III clinical trials of new therapies for patients with metastatic melanoma presented in June at the 2011 ASCO conference confirmed that vemurafenib and ipilimumab (Yervoy™) offer valuable new options for the disease.

  9. Valuable Internet Advertising and Customer Satisfaction Cycle(VIACSC)

    OpenAIRE

    Muhammad Awais; Tanzila Samin; Muhammad Bilal

    2012-01-01

    Now-a-days it is very important for the business persons to attract their target customers towards their products through valuable mode of promotion and communication. Increasing use of World Wide Web has completely changed the scenario of business sector. Customized products and services, customers preferences, @ and dot com craze have elevated the importance of internet advertising. This research paper investigates valuable internet advertising which will help to enhance the value of intern...

  10. Doll therapy: a therapeutic means to meet past attachment needs and diminish behaviours of concern in a person living with dementia--a case study approach.

    Science.gov (United States)

    Bisiani, Leah; Angus, Jocelyn

    2013-07-01

    The aim of this research study was to examine the impact of the provision of a lifelike baby doll as a therapeutic tool on the behaviour of a person living with dementia. Specifically, this single case study assessed the potential benefits, if any, of the use of doll therapy in reducing behaviours of concern such as anxiety and agitation that may be associated with observed attachment needs of a person living with dementia. A single case study of a female participant, with moderately advanced Alzheimer's disease, was the subject of this research. The case study used both qualitative and quantitative research design and methodology in data collection and analysis. Demonstrated that doll therapy was a positive intervention for the person living with dementia who was the participant in this research. The findings indicate a reduction in behaviours of concern related to the need for attachment and a considerable decline in levels of anxiety and agitation. There was extensive ongoing improvement in social interaction and communication. This research supports doll therapy as a therapeutic intervention that may be utilized within the ongoing care of some persons with dementia to meet needs for attachment and to reduce behaviours of concern. Despite some controversy on this topic, doll therapy should be considered as a therapeutic approach to further dementia care in light of this positive outcome.

  11. Restarting stalled autophagy a potential therapeutic approach for the lipid storage disorder, Niemann-Pick type C1 disease.

    Science.gov (United States)

    Sarkar, Sovan; Maetzel, Dorothea; Korolchuk, Viktor I; Jaenisch, Rudolf

    2014-06-01

    Autophagy is essential for cellular homeostasis and its dysfunction in human diseases has been implicated in the accumulation of misfolded protein and in cellular toxicity. We have recently shown impairment in autophagic flux in the lipid storage disorder, Niemann-Pick type C1 (NPC1) disease associated with abnormal cholesterol sequestration, where maturation of autophagosomes is impaired due to defective amphisome formation caused by failure in SNARE machinery. Abrogation of autophagy also causes cholesterol accumulation, suggesting that defective autophagic flux in NPC1 disease may act as a primary causative factor not only by imparting its deleterious effects, but also by increasing cholesterol load. However, cholesterol depletion treatment with HP-β-cyclodextrin impedes autophagy, whereas pharmacologically stimulating autophagy restores its function independent of amphisome formation. Of potential therapeutic relevance is that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may rescue both the cholesterol and autophagy defects in NPC1 disease.

  12. Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors.

    Science.gov (United States)

    El Harane, Nadia; Kervadec, Anaïs; Bellamy, Valérie; Pidial, Laetitia; Neametalla, Hany J; Perier, Marie-Cécile; Lima Correa, Bruna; Thiébault, Léa; Cagnard, Nicolas; Duché, Angéline; Brunaud, Camille; Lemitre, Mathilde; Gauthier, Jeanne; Bourdillon, Alexandra T; Renault, Marc P; Hovhannisyan, Yeranuhi; Paiva, Solenne; Colas, Alexandre R; Agbulut, Onnik; Hagège, Albert; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

    2018-05-21

    We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left

  13. Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach.

    Science.gov (United States)

    Chade, Alejandro R; Kelsen, Silvia

    2012-05-15

    Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to

  14. Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Jun eWang

    2014-03-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

  15. Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls.

    Science.gov (United States)

    Thevis, Mario; Schänzer, Wilhelm

    2014-12-01

    The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine. Among these compounds, low- and high-molecular mass substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500, hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non-peptidic (selective androgen receptor modulators, hypoxia-inducible factor stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic (cobalt) nature are considered and discussed in terms of specific requirements originating from physicochemical properties, concentration levels, metabolism, and their amenability for chromatographic-mass spectrometric or alternative detection methods. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches.

    Science.gov (United States)

    Morales, Inelia; Guzmán-Martínez, Leonardo; Cerda-Troncoso, Cristóbal; Farías, Gonzalo A; Maccioni, Ricardo B

    2014-01-01

    Alzheimer disease (AD) is the most common cause of dementia in people over 60 years old. The molecular and cellular alterations that trigger this disease are still diffuse, one of the reasons for the delay in finding an effective treatment. In the search for new targets to search for novel therapeutic avenues, clinical studies in patients who used anti-inflammatory drugs indicating a lower incidence of AD have been of value to support the neuroinflammatory hypothesis of the neurodegenerative processes and the role of innate immunity in this disease. Neuroinflammation appears to occur as a consequence of a series of damage signals, including trauma, infection, oxidative agents, redox iron, oligomers of τ and β-amyloid, etc. In this context, our theory of Neuroimmunomodulation focus on the link between neuronal damage and brain inflammatory process, mediated by the progressive activation of astrocytes and microglial cells with the consequent overproduction of proinflammatory agents. Here, we discuss about the role of microglial and astrocytic cells, the principal agents in neuroinflammation process, in the development of neurodegenerative diseases such as AD. In this context, we also evaluated the potential relevance of natural anti-inflammatory components, which include curcumin and the novel Andean Compound, as agents for AD prevention and as a coadjuvant for AD treatments.

  17. Neuroinflammation in the pathogenesis of Alzheimer´s disease. A rational framework for the search of novel therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Ricardo Benjamin Maccioni

    2014-04-01

    Full Text Available Alzheimer disease (AD is the most common cause of dementia in people over 60 years old. The molecular and cellular alterations that trigger this disease are still diffuse, one of the reasons for the delay in finding an effective treatment. In the search for new targets to search for novel therapeutic avenues, clinical studies in patients who used anti-inflammatory drugs indicating a lower incidence of AD have been of value to support the neuroinflammatory hypothesis of the neurodegenerative processes and the role of innate immunity in this disease. Neuroinflammation appears to occur as a consequence of a series of damage signals, including trauma, infection, oxidative agents, redox iron, oligomers of tau and beta amyloid, etc. In this context, our theory of Neuroimmunomodulation focus on the link between neuronal damage and brain inflammatory process, mediated by the progressive activation of astrocytes and microglial cells with the consequent overproduction of proinflammatory agents. Here, we discuss about the role of microglial and astrocytic cells, the principal agents in neuroinflammation process, in the development of neurodegenerative diseases such as AD. In this context, we also evaluated the potential relevance of natural anti-inflammatory components, which include curcumin and the novel Andean Compound, as agents for AD prevention and as a coadjuvant for AD treatments.

  18. Characterization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate Bayesian approach.

    Science.gov (United States)

    Fu, Zhibiao; Baker, Daniel; Cheng, Aili; Leighton, Julie; Appelbaum, Edward; Aon, Juan

    2016-05-01

    The principle of quality by design (QbD) has been widely applied to biopharmaceutical manufacturing processes. Process characterization is an essential step to implement the QbD concept to establish the design space and to define the proven acceptable ranges (PAR) for critical process parameters (CPPs). In this study, we present characterization of a Saccharomyces cerevisiae fermentation process using risk assessment analysis, statistical design of experiments (DoE), and the multivariate Bayesian predictive approach. The critical quality attributes (CQAs) and CPPs were identified with a risk assessment. The statistical model for each attribute was established using the results from the DoE study with consideration given to interactions between CPPs. Both the conventional overlapping contour plot and the multivariate Bayesian predictive approaches were used to establish the region of process operating conditions where all attributes met their specifications simultaneously. The quantitative Bayesian predictive approach was chosen to define the PARs for the CPPs, which apply to the manufacturing control strategy. Experience from the 10,000 L manufacturing scale process validation, including 64 continued process verification batches, indicates that the CPPs remain under a state of control and within the established PARs. The end product quality attributes were within their drug substance specifications. The probability generated with the Bayesian approach was also used as a tool to assess CPP deviations. This approach can be extended to develop other production process characterization and quantify a reliable operating region. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:799-812, 2016. © 2016 American Institute of Chemical Engineers.

  19. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Li-Ching Fan

    2015-09-01

    Full Text Available STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC. Our previous data demonstrated that regorafenib (Stivarga is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1 that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3Tyr705 level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43–induced apoptosis and decreased p-STAT3Tyr705 level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3Tyr705 level. These data suggest that SC-43–induced apoptosis mediated through the loss of p-STAT3Tyr705 was dependent on SHP-1 function. Importantly, SC-43–enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3Tyr705 signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3Tyr705expression in CRC patients (P = .038. Patients with strong SHP-1 and weak p-STAT3Tyr705 expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3Tyr705 expression (P = .029. In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC.

  20. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

    Science.gov (United States)

    Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

    2015-11-01

    Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

  1. The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles: Potential therapeutic approach for Alzheimer disease.

    Science.gov (United States)

    Mancini, Simona; Minniti, Stefania; Gregori, Maria; Sancini, Giulio; Cagnotto, Alfredo; Couraud, Pierre-Olivier; Ordóñez-Gutiérrez, Lara; Wandosell, Francisco; Salmona, Mario; Re, Francesca

    2016-01-01

    We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood-brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the 'brain' side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the 'blood' compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease. From the Clinical Editor: Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.

    Science.gov (United States)

    Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

    2013-01-01

    [Corrected] Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

  3. Genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

    Science.gov (United States)

    Scott, Robert A.; Freitag, Daniel F.; Li, Li; Chu, Audrey Y.; Surendran, Praveen; Young, Robin; Grarup, Niels; Stancáková, Alena; Chen, Yuning; V.Varga, Tibor; Yaghootkar, Hanieh; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Wessel, Jennifer; Wang, Shuai; Maruthur, Nisa; Michailidou, Kyriaki; Pirie, Ailith; van der Lee, Sven J.; Gillson, Christopher; Olama, Ali Amin Al; Amouyel, Philippe; Arriola, Larraitz; Arveiler, Dominique; Aviles-Olmos, Iciar; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Garcia, Sara Benlloch; Bis, Joshua C.; Blankenberg, Stefan; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Borecki, Ingrid B.; Bork-Jensen, Jette; Bowden, Sarah; Caldas, Carlos; Caslake, Muriel; Cupples, L. Adrienne; Cruchaga, Carlos; Czajkowski, Jacek; den Hoed, Marcel; Dunn, Janet A.; Earl, Helena M.; Ehret, Georg B.; Ferrannini, Ele; Ferrieres, Jean; Foltynie, Thomas; Ford, Ian; Forouhi, Nita G.; Gianfagna, Francesco; Gonzalez, Carlos; Grioni, Sara; Hiller, Louise; Jansson, Jan-Håkan; Jørgensen, Marit E.; Jukema, J. Wouter; Kaaks, Rudolf; Kee, Frank; Kerrison, Nicola D.; Key, Timothy J.; Kontto, Jukka; Kote-Jarai, Zsofia; Kraja, Aldi T.; Kuulasmaa, Kari; Kuusisto, Johanna; Linneberg, Allan; Liu, Chunyu; Marenne, Gaëlle; Mohlke, Karen L.; Morris, Andrew P.; Muir, Kenneth; Müller-Nurasyid, Martina; Munroe, Patricia B.; Navarro, Carmen; Nielsen, Sune F.; Nilsson, Peter M.; Nordestgaard, Børge G.; Packard, Chris J.; Palli, Domenico; Panico, Salvatore; Peloso, Gina M.; Perola, Markus; Peters, Annette; Poole, Christopher J.; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Salomaa, Veikko; Sánchez, María-José; Sattar, Naveed; Sharp, Stephen J.; Sims, Rebecca; Slimani, Nadia; Smith, Jennifer A.; Thompson, Deborah J.; Trompet, Stella; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Virtamo, Jarmo; Walker, Mark; Walter, Klaudia; Abraham, Jean E.; Amundadottir, Laufey T.; Aponte, Jennifer L.; Butterworth, Adam S.; Dupuis, Josée; Easton, Douglas F.; Eeles, Rosalind A.; Erdmann, Jeanette; Franks, Paul W.; Frayling, Timothy M.; Hansen, Torben; Howson, Joanna M. M.; Jørgensen, Torben; Kooner, Jaspal; Laakso, Markku; Langenberg, Claudia; McCarthy, Mark I.; Pankow, James S.; Pedersen, Oluf; Riboli, Elio; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schunkert, Heribert; Vollenweider, Peter; O'Rahilly, Stephen; Deloukas, Panos; Danesh, John; Goodarzi, Mark O.; Kathiresan, Sekar; Meigs, James B.; Ehm, Margaret G.; Wareham, Nicholas J.; Waterworth, Dawn M.

    2016-01-01

    Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to inform development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in 6 genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing, and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr;rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and lower T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomised controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. PMID:27252175

  4. A Genetic Approach to the Development of New Therapeutic Phages to Fight Pseudomonas Aeruginosa in Wound Infections

    Directory of Open Access Journals (Sweden)

    Elena Pleteneva

    2012-12-01

    Full Text Available Pseudomonas aeruginosa is a frequent participant in wound infections. Emergence of multiple antibiotic resistant strains has created significant problems in the treatment of infected wounds. Phage therapy (PT has been proposed as a possible alternative approach. Infected wounds are the perfect place for PT applications, since the basic condition for PT is ensured; namely, the direct contact of bacteria and their viruses. Plenty of virulent (“lytic” and temperate (“lysogenic” bacteriophages are known in P. aeruginosa. However, the number of virulent phage species acceptable for PT and their mutability are limited. Besides, there are different deviations in the behavior of virulent (and temperate phages from their expected canonical models of development. We consider some examples of non-canonical phage-bacterium interactions and the possibility of their use in PT. In addition, some optimal approaches to the development of phage therapy will be discussed from the point of view of a biologist, considering the danger of phage-assisted horizontal gene transfer (HGT, and from the point of view of a surgeon who has accepted the Hippocrates Oath to cure patients by all possible means. It is also time now to discuss the possible approaches in international cooperation for the development of PT. We think it would be advantageous to make phage therapy a kind of personalized medicine.

  5. Spatiotemporal PET Imaging of Dynamic Metabolic Changes After Therapeutic Approaches of Induced Pluripotent Stem Cells, Neuronal Stem Cells, and a Chinese Patent Medicine in Stroke.

    Science.gov (United States)

    Zhang, Hong; Song, Fahuan; Xu, Caiyun; Liu, Hao; Wang, Zefeng; Li, Jinhui; Wu, Shuang; YehuaShen; Chen, Yao; Zhu, Yunqi; Du, Ruili; Tian, Mei

    2015-11-01

    This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia-reperfusion injury. Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P PET imaging with (18)F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia-reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  6. Conceptos emergentes de tolerancia y autoinmunidad: Nuevos enfoques terapéuticos Tolerance and autoimmunity: Novel therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Esteban Ciliberti

    2009-10-01

    Full Text Available La función primaria del sistema inmune es resguardar al individuo de los patógenos potencialmente dañinos que invaden el medio ambiente en el cual nos desarrollamos. Este cuenta con dos grandes ramas, la inmunidad innata y la adaptativa, ambas con la propiedad de diferenciar lo peligroso de aquello inofensivo. Estos procesos se hallan regulados por mecanismos homeostáticos que constituyen la tolerancia inmunológica, a los fines de limitar aquellos procesos prolongados y silenciar los potencialmente autoagresivos. Ante la falla de estos mecanismos de control, surgen las enfermedades autoinmunes. Avances en el conocimiento de la fisiopatología de estas entidades, han abierto un nuevo capítulo en el terreno de la inmunofarmacología. Su prometedor potencial actualmente nos ofrece novedosas herramientas terapéuticas para controlar y atenuar el daño causado por este tipo de respuestas. No obstante, debe continuarse la investigación en el campo de los agentes biológicos, ya que ninguno de ellos se encuentra libre de inconvenientes. Seguramente, futuros hallazgos se concretarán en futuros aciertos. Y los aciertos, en Medicina, equivalen a esperanza.The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate

  7. Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes.

    Science.gov (United States)

    Sacramento, Joana F; Chew, Daniel J; Melo, Bernardete F; Donegá, Matteo; Dopson, Wesley; Guarino, Maria P; Robinson, Alison; Prieto-Lloret, Jesus; Patel, Sonal; Holinski, Bradley J; Ramnarain, Nishan; Pikov, Victor; Famm, Kristoffer; Conde, Silvia V

    2018-03-01

    A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function. Herein we characterise the ability of a novel bioelectronic application, classified as kilohertz frequency alternating current (KHFAC) modulation, to suppress neural signals within the CSN of rodents. Rats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60% lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces were bilaterally implanted in the CSNs and attached to an external pulse generator. The rats were then randomised to KHFAC or sham modulation groups. KHFAC modulation variables were defined acutely by respiratory and cardiac responses to hypoxia (10% O 2  + 90% N 2 ). Insulin sensitivity was evaluated periodically through an ITT and glucose tolerance by an OGTT. KHFAC modulation of the CSN, applied over 9 weeks, restored insulin sensitivity (constant of the insulin tolerance test [K ITT ] HFHSu sham, 2.56 ± 0.41% glucose/min; K ITT HFHSu KHFAC, 5.01 ± 0.52% glucose/min) and glucose tolerance (AUC HFHSu sham, 1278 ± 20.36 mmol/l × min; AUC HFHSu KHFAC, 1054.15 ± 62.64 mmol/l × min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin resistance and glucose intolerance returned to normal values within 5 weeks. KHFAC modulation of the CSN improves metabolic control in rat models of type 2 diabetes. These positive outcomes have significant translational potential as a novel therapeutic modality for the purpose of treating metabolic

  8. Sex- and gender-related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome: A review of the literature.

    Science.gov (United States)

    Pucci, Giacomo; Alcidi, Riccardo; Tap, Lisanne; Battista, Francesca; Mattace-Raso, Francesco; Schillaci, Giuseppe

    2017-06-01

    Metabolic syndrome (MS), a cluster of metabolic abnormalities linked to insulin-resistance and abdominal obesity, is associated with an increased risk of Type II diabetes mellitus (DM) and cardiovascular (CV) disease. Its prevalence is high, affecting 20%-30% of the general population, and increases with age in a sex-specific manner: in fact, while below 50 years it is slightly higher in men, it reverses after 50 years. The pronounced age-related increase in the prevalence of MS in women occurs as the result of several factors, which may be classified into sex- and gender-related factors. Sex-related factors, linked to genetical and biological pathways, are mainly driven by hyperandrogenism, insulin-resistance, and the associated increase in abdominal obesity and HDL-cholesterol reduction occurring after menopause. Gender-related factors are sensitive to social and cultural behaviors, dietary habits and psychosocial factors. Women are more prone than men to develop MS in response to work stress and low socio-economic status. Sex and gender differences in the prevalence of MS may translate in different CV risk associated. Prospective studies suggest that the CV risk in women with MS is not only equal but also superior to the CV risk of men with MS. This difference is mostly attenuated when adjusting for the presence of overt DM. Despite similar odds for CV events, the number of CV events may be higher in elderly women because of the higher prevalence of MS compared to men in this age group. Men and women may also have a differential response to treatments for MS, such as lifestyle measures and weight loss. Recent observations suggest that men are better responders than women to non-pharmaceutical therapeutic strategies aimed at reducing the prevalence of MS, although this should be confirmed in large-scale studies. The present review describes the impact of sex and gender on the prevalence, clinical presentation, prognostic significance and treatment of the MS

  9. Radiotherapy in conjunction with 7-hydroxystaurosporine: a multimodal approach with tumor pO2 as a potential marker of therapeutic response.

    Science.gov (United States)

    Khan, Nadeem; Mupparaju, Sriram P; Hou, Huagang; Lariviere, Jean P; Demidenko, Eugene; Swartz, Harold M; Eastman, Alan

    2009-11-01

    Checkpoint inhibitors potentially could be used to enhance cell killing by DNA-targeted therapeutic modalities such as radiotherapy. UCN-01 (7-hydroxystaurosporine) inhibits S and G2 checkpoint arrest in the cells of various malignant cell lines and has been investigated in combination with chemotherapy. However, little is known about its potential use in combination with radiotherapy. We report the effect of 20 Gy radiation given in conjunction with UCN-01 on the pO2 and growth of subcutaneous RIF-1 tumors. Multisite EPR oximetry was used for repeated, non-invasive tumor pO2 measurements. The effect of UCN-01 and/or 20 Gy on tumor pO2 and tumor volume was investigated to determine therapeutic outcomes. Untreated RIF-1 tumors were hypoxic with a tissue pO2 of 5-7 mmHg. Treatment with 20 Gy or UCN-01 significantly reduced tumor growth, and a modest increase in tumor pO2 was observed in tumors treated with 20 Gy. However, irradiation with 20 Gy 12 h after UCN-01 treatment resulted in a significant inhibition of tumor growth and a significant increase in tumor pO2 to 16-28 mmHg from day 1 onward compared to the control, UCN-01 or 20-Gy groups. Treatment with UCN-01 12 h after 20 Gy also led to a similar growth inhibition of the tumors and a similar increase in tumor pO2. The changes in tumor pO2 observed after the treatment correlated inversely with the tumor volume in the groups receiving UCN-01 with 20 Gy. This multimodal approach could be used to enhance the outcome of radiotherapy. Furthermore, tumor pO2 could be a potential marker of therapeutic response.

  10. Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus

    Directory of Open Access Journals (Sweden)

    Lilian S.R. Sadeck

    2014-12-01

    Full Text Available OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g with patent ductus arteriosus (PDA, from the Brazilian Neonatal Research Network (BNRN on: death, bronchopulmonary dysplasia (BPD, severe intraventricular hemorrhage (IVH III/IV, retinopathy of prematurity requiring surgical (ROPsur, necrotizing enterocolitis requiring surgery (NECsur, and death/BPD. METHODS: This was a multicentric cohort study, retrospective data collection, including newborns (BW < 1000 g with gestational age (GA < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment, G2 - pharmacologic (indomethacin or ibuprofen, G3 - surgical ligation (independent of previous treatment. Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II, respiratory distress syndrome (RDS, late sepsis (LS, mechanical ventilation (MV, surfactant (< 2 h of life, and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks, IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI; logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%, G2 - 205 (41.5%, and G3 - 102 (20.6%. The highest mortality was observed in G1 (51.3% and the lowest in G3 (14.7%. The highest frequencies of BPD36wks (70.6% and ROPsur were observed in G3 (23.5%. The lowest occurrence of

  11. Field Trips as Valuable Learning Experiences in Geography Courses

    Science.gov (United States)

    Krakowka, Amy Richmond

    2012-01-01

    Field trips have been acknowledged as valuable learning experiences in geography. This article uses Kolb's (1984) experiential learning model to discuss how students learn and how field trips can help enhance learning. Using Kolb's experiential learning theory as a guide in the design of field trips helps ensure that field trips contribute to…

  12. an assessment of timber trees producing valuable fruits and seeds ...

    African Journals Online (AJOL)

    User

    It is observed that most of the timber trees producing valuable fruits and seeds have low ... sector of the economy by providing major raw materials (saw logs, ... the trees also produce industrial raw materials like latex, ... villagers while avoiding some of the ecological costs of ..... enzymes of rats with carbon tetrachloride.

  13. Ravens reconcile after aggressive conflicts with valuable partners.

    Science.gov (United States)

    Fraser, Orlaith N; Bugnyar, Thomas

    2011-03-25

    Reconciliation, a post-conflict affiliative interaction between former opponents, is an important mechanism for reducing the costs of aggressive conflict in primates and some other mammals as it may repair the opponents' relationship and reduce post-conflict distress. Opponents who share a valuable relationship are expected to be more likely to reconcile as for such partners the benefits of relationship repair should outweigh the risk of renewed aggression. In birds, however, post-conflict behavior has thus far been marked by an apparent absence of reconciliation, suggested to result either from differing avian and mammalian strategies or because birds may not share valuable relationships with partners with whom they engage in aggressive conflict. Here, we demonstrate the occurrence of reconciliation in a group of captive subadult ravens (Corvus corax) and show that it is more likely to occur after conflicts between partners who share a valuable relationship. Furthermore, former opponents were less likely to engage in renewed aggression following reconciliation, suggesting that reconciliation repairs damage caused to their relationship by the preceding conflict. Our findings suggest not only that primate-like valuable relationships exist outside the pair bond in birds, but that such partners may employ the same mechanisms in birds as in primates to ensure that the benefits afforded by their relationships are maintained even when conflicts of interest escalate into aggression. These results provide further support for a convergent evolution of social strategies in avian and mammalian species.

  14. Salt Lakes of the African Rift System: A Valuable Research ...

    African Journals Online (AJOL)

    Salt Lakes of the African Rift System: A Valuable Research Opportunity for Insight into Nature's Concenrtated Multi-Electrolyte Science. JYN Philip, DMS Mosha. Abstract. The Tanzanian rift system salt lakes present significant cultural, ecological, recreational and economical values. Beyond the wealth of minerals, resources ...

  15. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2017-01-01

    Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

  16. Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus.

    Science.gov (United States)

    Sadeck, Lilian S R; Leone, Cléa R; Procianoy, Renato S; Guinsburg, Ruth; Marba, Sergio T M; Martinez, Francisco E; Rugolo, Ligia M S S; Moreira, M Elisabeth L; Fiori, Renato M; Ferrari, Ligia L; Menezes, Jucille A; Venzon, Paulyne S; Abdallah, Vânia Q S; Duarte, José Luiz M B; Nunes, Marynea V; Anchieta, Leni M; Alves Filho, Navantino

    2014-01-01

    To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. This was a multicentric, cohort study, retrospective data collection, including newborns (BW gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  17. Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.

    Science.gov (United States)

    Belaidi, Elise; Morand, Jessica; Gras, Emmanuelle; Pépin, Jean-Louis; Godin-Ribuot, Diane

    2016-12-01

    Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endothelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications

    Science.gov (United States)

    Belaidi, Elise; Morand, Jessica; Gras, Emmanuelle; Pépin, Jean-Louis; Godin-Ribuot, Diane

    2016-01-01

    Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endotelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients. PMID:27492897

  19. A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

    Science.gov (United States)

    Li, Jun; Nekka, Fahima

    2013-02-21

    The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for chronic kidney disease patients.

    Science.gov (United States)

    Aparicio, Michel; Bellizzi, Vincenzo; Chauveau, Philippe; Cupisti, Adamasco; Ecder, Tevfik; Fouque, Denis; Garneata, Liliana; Lin, Shanyan; Mitch, William E; Teplan, Vladimír; Zakar, Gábor; Yu, Xueqing

    2012-03-01

    Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): From preclinical findings to innovative therapeutic approaches in clinical settings.

    Science.gov (United States)

    Berardi, Andrea; Schelling, Gustav; Campolongo, Patrizia

    2016-09-01

    Post-Traumatic Stress Disorder (PTSD) is a psychiatric chronic disease developing in individuals after the experience of an intense and life-threatening traumatic event. The post-traumatic symptomatology encompasses alterations in memory processes, mood, anxiety and arousal. There is now consensus in considering the disease as an aberrant adaptation to traumatic stress. Pharmacological research, aimed at the discovery of new potential effective treatments, has lately directed its attention towards the "so-called" cognitive enhancers. This class of substances, by modulating cognitive processes involved in the development and/or persistence of the post-traumatic symptomatology, could be of great help in improving the outcome of psychotherapies and patients' prognosis. In this perspective, drugs acting on the endocannabinoid system are receiving great attention due to their dual ability to modulate memory processes on one hand, and to reduce anxiety and depression on the other. The purpose of the present review is to offer a thorough overview of both animal and human studies investigating the effects of cannabinoids on memory processes. First, we will briefly describe the characteristics of the endocannabinoid system and the most commonly used animal models of learning and memory. Then, studies investigating cannabinoid modulatory influences on memory consolidation, retrieval and extinction will be separately presented, and the potential benefits associated with each approach will be discussed. In the final section, we will review literature data reporting beneficial effects of cannabinoid drugs in PTSD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. [Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

    Science.gov (United States)

    Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

    2010-03-01

    Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  3. Tools for predicting the PK/PD of therapeutic proteins.

    Science.gov (United States)

    Diao, Lei; Meibohm, Bernd

    2015-07-01

    Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development. A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.

  4. Recent diagnostic and therapeutic approaches to prenatally and perinatally diagnosed hydronephrosis and their implementation in the University Clinical Hospital Mostar.

    Science.gov (United States)

    Mandić, Vjekoslav; Martinović, Vlatka; Kvesić, Ante; Bukvić, Nado; Skitarelić, Nataša; Brekalo, Zdrinko; Ivanković, Krunoslav; Šetka, Violeta

    2015-03-01

    A shift of the diagnostics of urological malformations towards the fetal age by means of ultrasound, especially hydronephrosis which, apart from reflux, is the most frequent developmental urological disorder, opened many dilemmas and debates. In the course of more than three decades the application of this diagnostic approach to the problem of hydrone- phrosis became a routine clinical practice in all modern clinics. In this paper we present the problems related to this diagnostic method and its delayed application in the Mostar University Clinical Hospital. Along with the exposition of a general approach to the problem of hydronephrosis we briefly present our modest collection of cases which points to the most recent trend of a vigorous medical development in this region, despite unfavorable overall conditions which prevailed so far. The observation included 56 children with prenatal, perinatal and early age determination of pyelon dilatation by means of ultrasonic exploration who were treated surgically. Of this number 32 (57.14%) were male, and 24 (42.86%) female children. Of the observed patients 56 had unilateral and 6 had bilateral pyelon dilatation so that 62 kidneys in all were observed and treated. The dilatation was determined prenatally in 24 (38.7%) out of 62 kidneys observed in all, in 7 (11.29%) the disorder was observed perinatally and in remaining 31 cases (49.9%) it manifested during early childhood, school age, even at the age of pre-puberty. Of the children with prenatally and perinatally determined dilatation, in 14 (45.16%) out of 31 (100.0%) observed kidneys the ap radius of the dilated pyelon was between 10-15 mm, and in 17 (54.84%) more than 15 mm. Along with other examinations (MAG3 and DMSA) the patients were followed-up by ultrasonic exploration of the observed kidney for 6 to 30 (average 18) months after postnatal diagnosis; the ultrasonic exploration was repeated in intervals of 6 months. Within 12 months of birth surgical intervention

  5. Recent advances in mass spectrometry-based approaches for proteomics and biologics: Great contribution for developing therapeutic antibodies.

    Science.gov (United States)

    Iwamoto, Noriko; Shimada, Takashi

    2018-05-01

    Since the turn of the century, mass spectrometry (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. The spectral data from MS contain various types of information. The benefits of improving the resolution of MS data include accurate molecular structural-derived information, and as a result, we can obtain a refined biomolecular structure determination in a sequential and large-scale manner. Moreover, in MS data, not only accurate structural information but also the generated ion amount plays an important rule. This progress has greatly contributed a research field that captures biological events as a system by comprehensively tracing the various changes in biomolecular dynamics. The sequential changes of proteome expression in biological pathways are very essential, and the amounts of the changes often directly become the targets of drug discovery or indicators of clinical efficacy. To take this proteomic approach, it is necessary to separate the individual MS spectra derived from each biomolecule in the complexed biological samples. MS itself is not so infinite to perform the all peak separation, and we should consider improving the methods for sample processing and purification to make them suitable for injection into MS. The above-described characteristics can only be achieved using MS with any analytical instrument. Moreover, MS is expected to be applied and expand into many fields, not only basic life sciences but also forensic medicine, plant sciences, materials, and natural products. In this review, we focus on the technical fundamentals and future aspects of the strategies for accurate structural identification, structure-indicated quantitation, and on the challenges for pharmacokinetics of high

  6. Tailored Beta-catenin mutational approach in extra-abdominal sporadic desmoid tumor patients without therapeutic intervention

    International Nuclear Information System (INIS)

    Broekhoven, Danique L.M. van; Grünhagenl, Dirk J.; Dalen, Thijs van; Coevorden, Frits van; Bonenkamp, Han J.; Been, Lukas B.; Bemelmans, Marc H.A.; Dijkstra, Sander D.S.; Colombo, Chiara; Gronchi, Alessandro; Verhoef, Cornelis

    2016-01-01

    The efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of aggressive fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall aggressive fibromatosis, while adhering to a “watchful waiting” policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor. GRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall aggressive fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization. This study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression. The GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number: NTR4714

  7. Valuable human capital: the aging health care worker.

    Science.gov (United States)

    Collins, Sandra K; Collins, Kevin S

    2006-01-01

    With the workforce growing older and the supply of younger workers diminishing, it is critical for health care managers to understand the factors necessary to capitalize on their vintage employees. Retaining this segment of the workforce has a multitude of benefits including the preservation of valuable intellectual capital, which is necessary to ensure that health care organizations maintain their competitive advantage in the consumer-driven market. Retaining the aging employee is possible if health care managers learn the motivators and training differences associated with this category of the workforce. These employees should be considered a valuable resource of human capital because without their extensive expertise, intense loyalty and work ethic, and superior customer service skills, health care organizations could suffer severe economic repercussions in the near future.

  8. VALUABLE AND ORIENTATION FOUNDATIONS OF EDUCATIONAL SYSTEM OF THE COUNTRY

    OpenAIRE

    Vladimir I. Zagvyazinsky

    2016-01-01

    The aim of the investigation is to show that in modern market conditions it is necessary to keep humanistic valuable and orientation installations of domestic education and not to allow its slipping on a line item of utilitarian, quickly achievable, but not long-term benefits. Theoretical significance. The author emphasizes value of forming of an ideal – harmonious development of the personality – and the collectivist beginnings for disclosure of potential of each school student, a student, a...

  9. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism.

    Science.gov (United States)

    Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart

    2015-04-01

    Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  12. Alternative therapeutic approach to renal-cell carcinoma: induction of apoptosis with combination of vitamin K3 and D-fraction.

    Science.gov (United States)

    Degen, Michael; Alexander, Bobby; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

    2013-12-01

    Because of a dismal prognosis for advanced renal-cell carcinoma (RCC), an alternative therapeutic approach, using vitamin K3 (VK3) and D-fraction (DF) was investigated. VK3 is a synthetic VK derivative and DF is a bioactive mushroom extract, and they have been shown to have antitumor activity. We examined if the combination of VK3 and DF would exhibit the improved anticancer effect on RCC in vitro. Human RCC, ACHN cell line, were treated with varying concentrations of VK3, DF, or a combination of the two. Cell viability was assessed at 72 hours by MTT assay. To explore the possible anticancer mechanism, studies on cell cycle, chromatin modifications, and apoptosis were conducted. VK3 alone led to a ~20% reduction in cell viability at 4 μM, while DF alone induced a 20% to 45% viability reduction at ≥ 500 μg/mL. A combination of VK3 (4 μM) and DF (300 μg/mL) led to a drastic >90% viability reduction, however. Cell cycle analysis indicated that VK3/DF treatment induced a G1 cell cycle arrest, accompanied by the up-regulation of p21(WAF1) and p27(Kip1). Histone deacetylase (HDAC) was also significantly (~60%) inactivated, indicating chromatin modifications. In addition, Western blot analysis revealed that the up-regulation of Bax and activation of poly-(ADP-ribose)-polymerase (PARP) were seen in VK3/DF-treated cells, indicating induction of apoptosis. The combination of VK3 and DF can lead to a profound reduction in ACHN cell viability, through a p21(WAF1)-mediated G1 cell cycle arrest, and ultimately induces apoptosis. Therefore, the combination of VK3/DF may have clinical implications as an alternative, improved therapeutic modality for advanced RCC.

  13. A simple bedside approach to therapeutic goals achievement during the management of deceased organ donors--An adapted version of the "VIP" approach.

    Science.gov (United States)

    Westphal, Glauco Adrieno

    2016-02-01

    The disproportion between the supply and demand of transplant organs could be alleviated by improving the quality of clinical management of deceased potential donors. As a large number of donor losses by cardiac arrest occur due to hemodynamic instability, without instituting all essential maintenance measures, it is likely that the application of simplified potential donor maintenance protocols will help to decrease potential donor losses and increase the supply of organs for transplantation. The Ventilation, Infusion and Pumping (VIP) strategy is a mnemonic method that brings together key aspects of the restoration of oxygen delivery to tissues during hemodynamic instability: adequate mechanical Ventilation, volume Infusion and evaluation of heart Pump effectiveness. The inclusion of the additional initials, "P" and "S," refers to Pharmacological treatment and Specificities involved in the etiology of shock. The use of simplified care standards can assist in adhering to essential potential donor management measures. Therefore, using a simplified method as the adapted VIP approach can contribute to improving management standards of potential organ donors and increasing the supply of organs for transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Extraction of toxic and valuable metals from foundry sands

    International Nuclear Information System (INIS)

    Vite T, J.

    1996-01-01

    There were extracted valuable metals from foundry sands such as: gold, platinum, silver, cobalt, germanium, nickel and zinc among others, as well as highly toxic metals such as chromium, lead, vanadium and arsenic. The extraction efficiency was up to 100% in some cases. For this reason there were obtained two patents at the United States, patent number 5,356,601, in October 1994, given for the developed process and patent number 5,376,000, in December 1994, obtained for the equipment employed. Therefore, the preliminary parameters for the installation of a pilot plant have also been developed. (Author)

  15. Toxin-Based Therapeutic Approaches

    OpenAIRE

    Itai Benhar; Assaf Shapira

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmac...

  16. A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

    Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

  17. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.

    Science.gov (United States)

    Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.

  18. Roles of HTLV-1 basic Zip Factor (HBZ in Viral Chronicity and Leukemic Transformation. Potential New Therapeutic Approaches to Prevent and Treat HTLV-1-Related Diseases

    Directory of Open Access Journals (Sweden)

    Jean-Michel Mesnard

    2015-12-01

    Full Text Available More than thirty years have passed since human T-cell leukemia virus type 1 (HTLV-1 was described as the first retrovirus to be the causative agent of a human cancer, adult T-cell leukemia (ATL, but the precise mechanism behind HTLV-1 pathogenesis still remains elusive. For more than two decades, the transforming ability of HTLV-1 has been exclusively associated to the viral transactivator Tax. Thirteen year ago, we first reported that the minus strand of HTLV-1 encoded for a basic Zip factor factor (HBZ, and since then several teams have underscored the importance of this antisense viral protein for the maintenance of a chronic infection and the proliferation of infected cells. More recently, we as well as others have demonstrated that HBZ has the potential to transform cells both in vitro and in vivo. In this review, we focus on the latest progress in our understanding of HBZ functions in chronicity and cellular transformation. We will discuss the involvement of this paradigm shift of HTLV-1 research on new therapeutic approaches to treat HTLV-1-related human diseases.

  19. Manipulation of tumor oxygenation and radiosensitivity through modification of cell respiration. A critical review of approaches and imaging biomarkers for therapeutic guidance.

    Science.gov (United States)

    Gallez, Bernard; Neveu, Marie-Aline; Danhier, Pierre; Jordan, Bénédicte F

    2017-08-01

    Tumor hypoxia has long been considered as a detrimental factor for the response to irradiation. In order to improve the sensitivity of tumors cells to radiation therapy, tumor hypoxia may theoretically be alleviated by increasing the oxygen delivery or by decreasing the oxygen consumption by tumor cells. Mathematical modelling suggested that decreasing the oxygen consumption should be more efficient than increasing oxygen delivery in order to alleviate tumor hypoxia. In this paper, we review several promising strategies targeting the mitochondrial respiration for which alleviation of tumor hypoxia and increase in sensitivity to irradiation have been demonstrated. Because the translation of these approaches into the clinical arena requires the use of pharmacodynamics biomarkers able to identify shift in oxygen consumption and tumor oxygenation, we also discuss the relative merits of imaging biomarkers (Positron Emission Tomography and Magnetic Resonance) that may be used for therapeutic guidance. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Trastorno oposicional desafiante: enfoques diagnóstico y terapéutico y trastornos asociados Oppositional defiant disorder: Diagnostic and therapeutic approaches, and associated disorders

    Directory of Open Access Journals (Sweden)

    Juan David Palacio Ortiz

    2008-01-01

    Full Text Available Se define el trastorno oposicional desafiante (TOD como un patrón recurrente de conducta negativista, desafiante, desobediente y hostil, dirigido a los padres y a las figuras de autoridad. Los estudios en países desarrollados han identificado factores cognitivos y conductuales errados, como los principales determinantes de una actitud negativa, opuesta y contraria a las normas establecidas; mientras que en países en vías de desarrollo, como Colombia, se destacan los factores ambientales como condicionantes de resiliencia y prosocialidad. En este artículo se presenta información general sobre el TOD, sus comorbilidades más frecuentes y su enfoque terapéutico.

    Oppositional-defiant disorder is defined by a repetitive pattern of negative, defiant, disobedient and hostile conduct, against parents and other authority figures. Surveys in developed countries have identified cognitive and misconduct risk factors as the main determinants of a negative attitude, opposed and contrary to social laws; but in developing countries, such as Colombia, environmental factors are the main determinants of resilience and prosociality. In this paper we present general information on TOD, its associated disorders, and its therapeutic approach

  1. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.

  2. Enfoque terapéutico de algunas enfermedades del tiroides en Pediatría Therapeutic approach to some thyroid diseases in pediatrics

    Directory of Open Access Journals (Sweden)

    Cecilia Pérez Gesen

    2012-12-01

    Full Text Available Las enfermedades del tiroides ocupan un lugar importante, por su frecuencia y variedad, entre las afecciones endocrinas del niño y el adolescente, y aunque puedan padecer las mismas enfermedades tiroideas del adulto, presentan afecciones específicas de la edad, cuyo diagnóstico y tratamiento adecuado puede prevenir los efectos devastadores e irreversibles que estas pueden producir. Se presenta, con interés de actualizar y establecer consenso, el enfoque terapéutico de algunas tiroidopatías de la infancia, en orden de importancia y frecuencia, como es el nódulo de tiroides, el bocio y el hipertiroidismo.Thyroid diseases hold an important place because of their frequency and variety in the endocrine diseases affecting the child and the adolescent. Although both can suffer the same thyroid diseases as the adults, there are specific illnesses of the age, the diagnosis and treatment of which may prevent the devastating and irreversible effects that they can bring. For the purpose of updating information and reaching a consensus, this paper presented the therapeutic approach to some thyroid diseases of the childhood by order of importance and frequency, such as the thyroid nodule, the goiter and the hyperthyroidism.

  3. Animals as an indicator of carbon sequestration and valuable landscapes

    Directory of Open Access Journals (Sweden)

    Jan Szyszko

    2011-05-01

    Full Text Available Possibilities of the assessment of a landscape with the use of succession development stages, monitored with the value of the Mean Individual Biomass (MIB of carabid beetles and the occurrence of bird species are discussed on the basis of an example from Poland. Higher variability of the MIB value in space signifies a greater biodiversity. Apart from the variability of MIB, it is suggested to adopt the occurrence of the following animals as indicators, (in the order of importance, representing underlying valuable landscapes: black stork, lesser spotted eagle, white-tailed eagle, wolf, crane and white stork. The higher number of these species and their greater density indicate a higher value of the landscape for biodiversity and ecosystem services, especially carbon sequestration. All these indicators may be useful to assess measures for sustainable land use.

  4. Metagenomes provide valuable comparative information on soil microeukaryotes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Stenbæk, Jonas; Santos, Susana

    2016-01-01

    has been identified. Our analyses suggest that publicly available metagenome data can provide valuable information on soil microeukaryotes for comparative purposes when handled appropriately, complementing the current view provided by ribosomal amplicon sequencing methods......., providing microbiologists with substantial amounts of accessible information. We took advantage of public metagenomes in order to investigate microeukaryote communities in a well characterized grassland soil. The data gathered allowed the evaluation of several factors impacting the community structure......, including the DNA extraction method, the database choice and also the annotation procedure. While most studies on soil microeukaryotes are based on sequencing of PCR-amplified taxonomic markers (18S rRNA genes, ITS regions), this work represents, to our knowledge, the first report based solely...

  5. CORRELATION LINKS BETWEEN SOME ECONOMICALLY VALUABLE SIGNS IN BROCCOLI

    Directory of Open Access Journals (Sweden)

    E. A. Zablotskaya

    2018-01-01

    Full Text Available The study of the correlation relationship between the signs, the informativeness of the indicators makes it possible to conduct a preliminary assessment of the plants and more objectively to identify forms with high economically valuable characteristics. Their integrated assessment will identify the best source material for further selection. In literary sources, information on the correlation in broccoli between yields and its elements are not the same. The purpose of our study was to analyze the contingency of various traits and to identify significant correlation links between quantitative traits in broccoli hybrids (42 samples. They were obtained using doubled haploid lines (DH-line of early maturity at 2 planting dates (spring and summer. Studies were conducted in the Odintsovo district of the Moscow region in field experience in 2015, 2016. Significant influence on growth and development was provided by the developing weather conditions during the growing period. The fluctuation of humidification and temperature conditions differed significantly during the years of study and the time of planting, which is an important circumstance for analyzing the data obtained. Based on the results of the research, it was concluded that the value of the correlation coefficient and the strength of the correlation relationship between the characteristics (mass, diameter, head height, plant height, vegetation period are different and depend on the set of test specimens and growing conditions. A significant stable manifestation of positive correlation was revealed during all the years of research and the time of planting between the diameter and mass of the head (r = 0.45-0.96. The variability of the correlation of other economically valuable traits is marked. 

  6. From therapeutic patient education principles to educative attitude: the perceptions of health care professionals – a pragmatic approach for defining competencies and resources

    Directory of Open Access Journals (Sweden)

    Pétré B

    2017-03-01

    Full Text Available Benoit Pétré,1 Remi Gagnayre,2 Vincent De Andrade,2 Olivier Ziegler,3 Michèle Guillaume1 1Department of Public Health, University of Liège, Liège, Belgium; 2Educations and Health Practices Laboratory (LEPS, (EA 3412, UFR SMBH, Paris 13 University, Sorbonne Paris Cite, Bobigny, 3Department of Diabetes, Metabolic diseases and Nutrition, Nancy University Hospital, Nancy, France Abstract: Educative attitude is an essential, if implicit, aspect of training to acquire competency in therapeutic patient education (TPE. With multiple (or nonexistent definitions in the literature, however, the concept needs clarification. The primary aim of this study was to analyze the representations and transformations experienced by health care professionals in the course of TPE training in order to characterize educative attitude. We conducted an exploratory qualitative study using several narrative research-based tools with participants of two TPE continuing education courses. We then performed an inductive thematic analysis. Thirty-three people participated in the study; the majority were women (n=29, nurses (n=17 working in a hospital setting (n=28. Seven categories of statements were identified: time-related (“the right moment, how much time it takes”, the benefits of TPE (to health care professionals’ personal well-being, emotions and feelings (quality of exchanges, sharing, the professional nature of TPE (educational competencies required, the holistic, interdisciplinary approach (complexity of the person and value of teamwork, the educational nature of the care relationship (education an integral part of care and the ethical dimension (introspection essential. The first three components appear fairly innovative, at least in formulation. The study’s originality rests primarily in its choice of participants – highly motivated novices who expressed themselves in a completely nontheoretical way. Health models see attitude as critical for adopting a

  7. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  8. Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

    International Nuclear Information System (INIS)

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

    2014-01-01

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.

  9. Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Singapore); Synthetic Biology Research Program, National University of Singapore, Singapore (Singapore); Leong, Susanna Su Jan [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Singapore); Synthetic Biology Research Program, National University of Singapore, Singapore (Singapore); Singapore Institute of Technology, Singapore (Singapore); Chang, Matthew Wook, E-mail: bchcmw@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Singapore); Synthetic Biology Research Program, National University of Singapore, Singapore (Singapore)

    2014-12-23

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.

  10. Technologies for Extracting Valuable Metals and Compounds from Geothermal Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen [SIMBOL Materials

    2014-04-30

    Executive Summary Simbol Materials studied various methods of extracting valuable minerals from geothermal brines in the Imperial Valley of California, focusing on the extraction of lithium, manganese, zinc and potassium. New methods were explored for managing the potential impact of silica fouling on mineral extraction equipment, and for converting silica management by-products into commercial products.` Studies at the laboratory and bench scale focused on manganese, zinc and potassium extraction and the conversion of silica management by-products into valuable commercial products. The processes for extracting lithium and producing lithium carbonate and lithium hydroxide products were developed at the laboratory scale and scaled up to pilot-scale. Several sorbents designed to extract lithium as lithium chloride from geothermal brine were developed at the laboratory scale and subsequently scaled-up for testing in the lithium extraction pilot plant. Lithium The results of the lithium studies generated the confidence for Simbol to scale its process to commercial operation. The key steps of the process were demonstrated during its development at pilot scale: 1. Silica management. 2. Lithium extraction. 3. Purification. 4. Concentration. 5. Conversion into lithium hydroxide and lithium carbonate products. Results show that greater than 95% of the lithium can be extracted from geothermal brine as lithium chloride, and that the chemical yield in converting lithium chloride to lithium hydroxide and lithium carbonate products is greater than 90%. The product purity produced from the process is consistent with battery grade lithium carbonate and lithium hydroxide. Manganese and zinc Processes for the extraction of zinc and manganese from geothermal brine were developed. It was shown that they could be converted into zinc metal and electrolytic manganese dioxide after purification. These processes were evaluated for their economic potential, and at the present time Simbol

  11. Inhibiting trophoblast PAR-1 overexpression suppresses sFlt-1-induced anti-angiogenesis and abnormal vascular remodeling: a possible therapeutic approach for preeclampsia.

    Science.gov (United States)

    Zhao, Yin; Zheng, YanFang; Liu, XiaoXia; Luo, QingQing; Wu, Di; Liu, XiaoPing; Zou, Li

    2018-03-01

    Is it possible to improve vascular remodeling by inhibiting the excessive expression of protease-activated receptor 1 (PAR-1) in trophoblast of abnormal placenta? Inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis and vascular remodeling, offering an alternative therapeutic approach for preeclampsia. PAR-1 is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in trophoblast via the activation of PAR-1. It is reported that the expression of both thrombin and PAR-1 expression are increased in placentas of preeclampsia patients compared with normal placentas. Trophoblast cells were transfected with PAR-1 short hairpin RNA (shRNA) or PAR-1 overexpression plasmids in vitro. Tube formation assays and a villus-decidua co-culture system were used to study the effect of PAR-1 inhibition on placental angiogenesis and vascular remodeling, respectively. Placentas from rats with preeclampsia were transfected with PAR-1 shRNA to confirm the effect of inhibiting PAR-1 overexpression in placenta. The trophoblast cell line HTR-8/SVneo was transfected with PAR-1 shRNA or PAR-1 overexpression plasmids. After 48 h, supernatant was collected and the level of sFlt-1 secretion was measured by ELISA. Human umbilical cord epithelial cells and a villus-decidua co-culture system were treated with conditioned media to study the effect of PAR-1 inhibition on tube formation and villi vascular remodeling. A preeclampsia rat model was established by intraperitoneal injection of L-NAME. Plasmids were injected into the placenta of the preeclampsia rats and systolic blood pressure was measured on Days 15 and 19. The effect of different treatments was evaluated by proteinuria, placental weights, fetal weights and fetal numbers in study and control groups. The level of serum sFlt-1 in rats with preeclampsia was also measured. Changes in the placenta microvessels were studied by histopathological staining. PAR-1 shRNA inhibited PAR-1 expression and

  12. Conversion of waste polystyrene through catalytic degradation into valuable products

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Jasmin; Jan, Muhammad Rasul; Adnan [University of Peshawar, Peshawar (Pakistan)

    2014-08-15

    Waste expanded polystyrene (EPS) represents a source of valuable chemical products like styrene and other aromatics. The catalytic degradation was carried out in a batch reactor with a mixture of polystyrene (PS) and catalyst at 450 .deg. C for 30 min in case of Mg and at 400 .deg. C for 2 h both for MgO and MgCO{sub 3} catalysts. At optimum degradation conditions, EPS was degraded into 82.20±3.80 wt%, 91.60±0.20 wt% and 81.80±0.53 wt% liquid with Mg, MgO and MgCO{sub 3} catalysts, respectively. The liquid products obtained were separated into different fractions by fractional distillation. The liquid fractions obtained with three catalysts were compared, and characterized using GC-MS. Maximum conversion of EPS into styrene monomer (66.6 wt%) was achieved with Mg catalyst, and an increase in selectivity of compounds was also observed. The major fraction at 145 .deg. C showed the properties of styrene monomer. The results showed that among the catalysts used, Mg was found to be the most effective catalyst for selective conversion into styrene monomer as value added product.

  13. GC Analyses of Salvia Seeds as Valuable Essential Oil Source

    Directory of Open Access Journals (Sweden)

    Mouna Ben Taârit

    2014-01-01

    Full Text Available The essential oils of seeds of Salvia verbenaca, Salvia officinalis, and Salvia sclarea were obtained by hydrodistillation and analyzed by gas chromatography (GC and GC-mass spectrometry. The oil yields (w/w were 0.050, 0.047, and 0.045% in S. verbenaca, S. sclarea, and S. officinalis, respectively. Seventy-five compounds were identified. The essential oil composition of S. verbenaca seeds showed that over 57% of the detected compounds were oxygenated monoterpenes followed by sesquiterpenes (24.04% and labdane type diterpenes (5.61%. The main essential oil constituents were camphor (38.94%, caryophyllene oxide (7.28%, and 13-epi-manool (5.61%, while those of essential oil of S. officinalis were α-thujone (14.77%, camphor (13.08%, and 1,8-cineole (6.66%. In samples of S. sclarea, essential oil consists mainly of linalool (24.25%, α-thujene (7.48%, linalyl acetate (6.90%, germacrene-D (5.88%, bicyclogermacrene (4.29%, and α-copaene (4.08%. This variability leads to a large range of naturally occurring volatile compounds with valuable industrial and pharmaceutical outlets.

  14. Sea Buckthorn Oil—A Valuable Source for Cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Marijana Koskovac

    2017-10-01

    Full Text Available Sea buckthorn (Hippophae rhamnoides L., Elaeagnaceae. is a thorny shrub that has small, yellow to dark orange, soft, juicy berries. Due to hydrophilic and lipophilic ingredients, berries have been used as food and medicine. Sea buckthorn (SB oil derived from berries is a source of valuable ingredients for cosmeceuticals. The unique combination of SB oil ingredients, in qualitative and quantitative aspects, provides multiple benefits of SB oil for internal and external use. Externally, SB oil can be applied in both healthy and damaged skin (burns or skin damage of different etiology, as it has good wound healing properties. Due to the well-balanced content of fatty acids, carotenoids, and vitamins, SB oil may be incorporated in cosmeceuticals for dry, flaky, burned, irritated, or rapidly ageing skin. There have been more than 100 ingredients identified in SB oil, some of which are rare in the plant kingdom (e.g., the ratio of palmitoleic to γ-linolenic acid. This review discusses facts related to the origin and properties of SB oil that make it suitable for cosmeceutical formulation.

  15. VALUABLE AND ORIENTATION FOUNDATIONS OF EDUCATIONAL SYSTEM OF THE COUNTRY

    Directory of Open Access Journals (Sweden)

    Vladimir I. Zagvyazinsky

    2016-01-01

    Full Text Available The aim of the investigation is to show that in modern market conditions it is necessary to keep humanistic valuable and orientation installations of domestic education and not to allow its slipping on a line item of utilitarian, quickly achievable, but not long-term benefits. Theoretical significance. The author emphasizes value of forming of an ideal – harmonious development of the personality – and the collectivist beginnings for disclosure of potential of each school student, a student, a worker, a specialist; also the author emphasizes on requirement of the stimulating, but not strictly regulated management of education. It is proved that copying of the western model of consecutive individualization of education without preserving the collectivist beginning is unacceptable in training, especially in educational process. In more general, strategic foreshortening this means that parity of the problem resolution of economy and the social sphere with which it is impossible to cope without support and educational development and first of all education, it is especially important during the periods of economic crises and stagnation for providing an exit from a crisis state on the basis of the advancing preparation and rational use of the personnel which neatly are considered as a human capital. Practical significance. Resources and positive tendencies in a development of education, especially elite, and also educational systems of some territories, including the Tyumen region where traditions of the enthusiasts-pioneers mastering the remote territories of oil and gas fields remain are shown. 

  16. Rabeto plus: a valuable drug for managing functional dyspepsia.

    Science.gov (United States)

    Ghosh, Asim; Halder, Susanta; Mandal, Sanjoy; Mandal, Arpan; Basu, Mitali; Dabholkar, Pareen

    2008-11-01

    The aim of the study was to evaluate and document the efficacy and tolerability of rabeto plus (FDC of rabeprazole and itopride) in management of functional dyspepsia. It was an open, prospective, non-comparative, multidose study. The patients with functional dyspepsia (NERD or non-erosive reflux disease) attending OPD of a leading, tertiary care, teaching hospital in West Bengal (BS Medical College, Bankura) were inducted in the study. A total of 46 adult patients of either sex with functional dyspepsia and a clinical diagnosis of NERD were given 1 capsule of rabeto plus before breakfast, for up to 4 weeks. Primary efficacy variables were relief from symptoms of heartburn, nausea, vomiting, waterbrash and fullness. Secondary efficacy variables were global assessment of efficacy and toleration by patients and treating physicians. The tolerability was assessed on the basis of record of spontaneously reported adverse events with their nature, intensity and outcome. Out of 55 patients enrolled in the study, 46 completed the study as planned, while 9 patients were lost to follow-up (dropped). Most patients reported near total symptom relief by the end of study. Total symptom score showed remarkable and significant improvement from baseline to end of the study. Importantly, none of the patients reported any side-effect. All participants tolerated the drug well. Moreover, response to study drug was rated as excellent or good by over 93% patients and their treating physicians. This means that 9 out 10 patients receiving rabeto plus reported desired symptom relief from dyspepsia. Thus it was concluded that rabeto plus is a valuable drug for treatment of functional dyspepsia or NERD.

  17. Whey-derived valuable products obtained by microbial fermentation.

    Science.gov (United States)

    Pescuma, Micaela; de Valdez, Graciela Font; Mozzi, Fernanda

    2015-08-01

    Whey, the main by-product of the cheese industry, is considered as an important pollutant due to its high chemical and biological oxygen demand. Whey, often considered as waste, has high nutritional value and can be used to obtain value-added products, although some of them need expensive enzymatic synthesis. An economical alternative to transform whey into valuable products is through bacterial or yeast fermentations and by accumulation during algae growth. Fermentative processes can be applied either to produce individual compounds or to formulate new foods and beverages. In the first case, a considerable amount of research has been directed to obtain biofuels able to replace those derived from petrol. In addition, the possibility of replacing petrol-derived plastics by biodegradable polymers synthesized during bacterial fermentation of whey has been sought. Further, the ability of different organisms to produce metabolites commonly used in the food and pharmaceutical industries (i.e., lactic acid, lactobionic acid, polysaccharides, etc.) using whey as growth substrate has been studied. On the other hand, new low-cost functional whey-based foods and beverages leveraging the high nutritional quality of whey have been formulated, highlighting the health-promoting effects of fermented whey-derived products. This review aims to gather the multiple uses of whey as sustainable raw material for the production of individual compounds, foods, and beverages by microbial fermentation. This is the first work to give an overview on the microbial transformation of whey as raw material into a large repertoire of industrially relevant foods and products.

  18. Recycled Cell Phones - A Treasure Trove of Valuable Metals

    Science.gov (United States)

    Sullivan, Daniel E.

    2006-01-01

    This U.S. Geological Survey (USGS) Fact Sheet examines the potential value of recycling the metals found in obsolete cell phones. Cell phones seem ubiquitous in the United States and commonplace throughout most of the world. There were approximately 1 billion cell phones in use worldwide in 2002. In the United States, the number of cell phone subscribers increased from 340,000 in 1985 to 180 million in 2004. Worldwide, cell phone sales have increased from slightly more than 100 million units per year in 1997 to an estimated 779 million units per year in 2005. Cell phone sales are projected to exceed 1 billion units per year in 2009, with an estimated 2.6 billion cell phones in use by the end of that year. The U.S. Environmental Protection Agency estimated that, by 2005, as many as 130 million cell phones would be retired annually in the United States. The nonprofit organization INFORM, Inc., anticipated that, by 2005, a total of 500 million obsolete cell phones would have accumulated in consumers' desk drawers, store rooms, or other storage, awaiting disposal. Typically, cell phones are used for only 1 1/2 years before being replaced. Less than 1 percent of the millions of cell phones retired and discarded annually are recycled. When large numbers of cell phones become obsolete, large quantities of valuable metals end up either in storage or in landfills. The amount of metals potentially recoverable would make a significant addition to total metals recovered from recycling in the United States and would supplement virgin metals derived from mining.

  19. Building Your Evaluation Business into a Valuable Asset

    Science.gov (United States)

    Hwalek, Melanie; Barber, Gregory J.

    2006-01-01

    Determining what will occur with a consulting practice becomes a more pressing concern as an evaluator approaches the age of retirement. Typically independent consultants do not have the pension planning services readily available to evaluators in academic settings, governmental agencies, or large corporations. Without prompts such as automatic…

  20. An integral approach to the etiopathogenesis of human neurodegenerative diseases (HNDDs and cancer. Possible therapeutic consequences within the frame of the trophic factor withdrawal syndrome (TFWS

    Directory of Open Access Journals (Sweden)

    Enrique Meléndez Hevia

    2008-10-01

    Full Text Available Salvador Harguindey1, Gorka Orive2,6, Ramón Cacabelos3, Enrique Meléndez Hevia4, Ramón Díaz de Otazu5, et al1Institute of Clinical Biology and Metabolism, Vitoria, Spain; 2Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of The Basque Country, Vitoria, Spain; 3Department of Clinical Neuroscience, EuroEspes Biomedical Research Center, Bergondo, La Coruña, Spain; 4Institute for Cellular Metabolism, Tenerife, Spain; 5Department of Pathology, Hospital Txagorritxu, Vitoria, Spain; 6Biotechnology Institute (BTI, Vitoria, SpainAbstract: A novel and integral approach to the understanding of human neurodegenerative diseases (HNDDs and cancer based upon the disruption of the intracellular dynamics of the hydrogen ion (H+ and its physiopathology, is advanced. From an etiopathological perspective, the activity and/or deficiency of different growth factors (GFs in these pathologies are studied, and their relationships to intracellular acid-base homeostasis reviewed. Growth and trophic factor withdrawal in HNDDs indicate the need to further investigate the potential utilization of certain GFs in the treatment of Alzheimer disease and other neurodegenerative diseases.  Platelet abnormalities and the therapeutic potential of platelet-derived growth factors in these pathologies, either through platelet transfusions or other clinical methods, are considered. Finally, the etiopathogenic mechanisms of apoptosis and antiapoptosis in HNDDs and cancer are viewed as opposite biochemical and biological disorders of cellular acid-base balance and their secondary effects on intracellular signaling pathways and aberrant cell metabolism are considered in the light of the both the seminal and most recent data available. The “trophic factor withdrawal syndrome” is described for the first time in English-speaking medical literature, as well as a Darwinian-like interpretation of cellular behavior related to specific and nonspecific

  1. Catalytic conversion of CO2 into valuable products

    International Nuclear Information System (INIS)

    Pham-Huu, C.; Ledoux, M.J.

    2008-01-01

    inertness the recovery of the active phase is extremely easy, i.e. acidic or basic washing, which reduce the cost investment of the process for the final spent catalyst disposal and the fully re-use of the support. The high thermal conductivity of the SiC support could also allow the reduction of the temperature loss during the reaction taken into account the high endothermicity of the reaction. The aim of the presentation is to report the synthesis and use of SiC-based catalyst for CO 2 reforming which allows the conversion of CO 2 into a more valuable products for further fuel processing via the Fischer-Tropsch synthesis

  2. Microbial Leaching of Some Valuable Elements From Egyptian Phosphate Rock

    International Nuclear Information System (INIS)

    Kamal, H.M.; Hassanein, R.A.; Mahdy, H.M.A.; Mahmoud, K.F.; Abouzeid, M.A.

    2012-01-01

    Four phosphate rock samples representing different phosphate mineralization modes in Egypt were selected from Abu Tartar, Nile valley and Red sea areas. Factors affecting the phosphate rock solubilization and some of the contained valuable elements by Aspergillus niger, Penicillium sp. and Pseudomonas fluorescence, were studied with especial orientation towards the completion of phosphate rock samples solubilization especially die low grade one. Effect of nitrogen source type on leaching efficiency by Aspergillus niger when two nitrogen sources on the phosphate bioleaching efficiency, it is clear that the ammonium chloride is more favorable as nitrogen source than sodium nitrate in the bioleaching of phosphate rocks. When Aspergillus niger was applied under die following conditions: 50 g/1 of sucrose as a carbon source, 0.1 N of ammonium chloride as a nitrogen source, 10 days incubation period, 0.5% solid: liquid ratio for P 2 O 5 and 5% for U and REE and - 270 mesh of grain size. The optimum leaching of P 2 O 5 , U and REE from phosphate rock samples reached (23.27%, 17.4%, 11.4%, respectively), while at -60 mesh they reached to 16.58%, 28.9%, 30.2% respectively. The optimum conditions for the maximal leaching efficiencies of P 2 O 5 , U and REE when applying the Penicillium sp. from the phosphate rock samples were: 100 g/1 of sucrose as a carbon source for P 2 O 5 and U and 10 g/1 for REE, 7,15 and 10 days incubation period for P 2 O 5 , U and REE, respectively, 0.5% solid: liquid ratio for P 2 O 5 and 5% for U and REE. Finally, the application of phosphate rock samples grinded to -270 mesh of grain size for P 2 O 5 and (-60 to -140) for U and REE. The studied leaching efficiency of P 2 O 5 , U and REE gave at -270 mesh 33.66%, 24.3%, 15.9% respectively, while at -60 mesh they gave 33.76%, 26.7%, 17.8% and at -140 mesh gave 31.32%, 27.9%, 17.6%, respectively.The optimum conditions for the P 2 O 5 leaching efficiency when applying the Pseudomonas fluorescence were

  3. Therapeutic Inertia and Treatment Intensification.

    Science.gov (United States)

    Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

    2018-01-29

    This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

  4. Self-Inflicted Lesions in Dermatology: A Management and Therapeutic Approach - A Position Paper From the European Society for Dermatology and Psychiatry

    NARCIS (Netherlands)

    Tomas-Aragones, Lucia; Consoli, Silla M.; Consoli, Sylvie G.; Poot, Francoise; Taube, Klaus-Michael; Linder, M. Dennis; Jemec, Gregor B. E.; Szepietowski, Jacek C.; de Korte, John; Lvov, Andrey; Gieler, Uwe

    2017-01-01

    The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new

  5. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

    LENUS (Irish Health Repository)

    Byrne, A T

    2009-11-03

    Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

  6. GMO quantification: valuable experience and insights for the future.

    Science.gov (United States)

    Milavec, Mojca; Dobnik, David; Yang, Litao; Zhang, Dabing; Gruden, Kristina; Zel, Jana

    2014-10-01

    Cultivation and marketing of genetically modified organisms (GMOs) have been unevenly adopted worldwide. To facilitate international trade and to provide information to consumers, labelling requirements have been set up in many countries. Quantitative real-time polymerase chain reaction (qPCR) is currently the method of choice for detection, identification and quantification of GMOs. This has been critically assessed and the requirements for the method performance have been set. Nevertheless, there are challenges that should still be highlighted, such as measuring the quantity and quality of DNA, and determining the qPCR efficiency, possible sequence mismatches, characteristics of taxon-specific genes and appropriate units of measurement, as these remain potential sources of measurement uncertainty. To overcome these problems and to cope with the continuous increase in the number and variety of GMOs, new approaches are needed. Statistical strategies of quantification have already been proposed and expanded with the development of digital PCR. The first attempts have been made to use new generation sequencing also for quantitative purposes, although accurate quantification of the contents of GMOs using this technology is still a challenge for the future, and especially for mixed samples. New approaches are needed also for the quantification of stacks, and for potential quantification of organisms produced by new plant breeding techniques.

  7. Human Factor in Therapeutic Relationship

    Directory of Open Access Journals (Sweden)

    Ramazan Akdogan

    2011-03-01

    Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

  8. Technologies for the bioconversion of methane into more valuable products.

    Science.gov (United States)

    Cantera, Sara; Muñoz, Raúl; Lebrero, Raquel; López, Juan Carlos; Rodríguez, Yadira; García-Encina, Pedro Antonio

    2018-04-01

    Methane, with a global warming potential twenty five times higher than that of CO 2 is the second most important greenhouse gas emitted nowadays. Its bioconversion into microbial molecules with a high retail value in the industry offers a potential cost-efficient and environmentally friendly solution for mitigating anthropogenic diluted CH 4 -laden streams. Methane bio-refinery for the production of different compounds such as ectoine, feed proteins, biofuels, bioplastics and polysaccharides, apart from new bioproducts characteristic of methanotrophic bacteria, has been recently tested in discontinuous and continuous bioreactors with promising results. This review constitutes a critical discussion about the state-of-the-art of the potential and research niches of biotechnologies applied in a CH 4 biorefinery approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

    Science.gov (United States)

    Kambalapally, Swetha Reddy

    The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as

  10. Is staged external fixation a valuable strategy for war injuries to the limbs?

    Science.gov (United States)

    Lerner, Alexander; Fodor, Lucian; Soudry, Michael

    2006-07-01

    High-energy weapons or blast injuries usually result in substantial tissue damage and are serious medical and public health problems. We report our experience with staged external fixation for war injuries to the extremities. Forty-seven patients with 64 high-energy limb fractures caused by war weapons were retrospectively reviewed. The fractures were associated with severe soft tissue damage. There were 14 Gustilo-Anderson Type IIIA fractures, 40 Type IIIB fractures, and 10 Type IIIC fractures. Soft tissue débridement followed by axial realignment of the fractured bones with immediate skeletal stabilization using the AO/ASIF unilateral tubular external fixator was performed on the day of admission. The primary tubular fixators were exchanged 5 to 7 days later for Ilizarov frames. Delayed primary closure, skin grafts, or flaps were used for soft tissue coverage. The mean followup was 40 months, and the Ilizarov/hybrid external fixator was the definitive treatment in all patients. Bone union was achieved at an average of 8 months in 58 (90.6%) fractures. Three patients had nonunions and one patient required an amputation. Two patients were lost to followup. Staged external fixation is a valuable strategy for treatment of war injuries to the extremities. Therapeutic study, Level IV. See the Guidelines for Authors for a complete description of levels of evidence.

  11. Caprylic Triglyceride as a Novel Therapeutic Approach to Effectively Improve the Performance and Attenuate the Symptoms Due to the Motor Neuron Loss in ALS Disease

    OpenAIRE

    Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approac...

  12. Digital Risk Inventory and Evaluation (RIE) : a Dutch approach offering valuable support for small business owners

    NARCIS (Netherlands)

    Meeuwsen, J.M.

    2008-01-01

    The Dutch Working Conditions Act requires employers to perform a Risk Inventory and Evaluation (RIE). Until recently, small business owners (SMEs) in particular were unhappy about this rather time-consuming obligation. However, the introduction of digital RIE instruments disseminated through the web

  13. Instrumental neutron activation analysis, a valuable link in chemical metrology

    International Nuclear Information System (INIS)

    Zeisler, R.; Lindstrom, R.M.; Greenberg, R.R.

    2002-01-01

    Instrumental neutron activation analysis (INAA) is sufficiently versatile to establish a direct link to the amount of substance determined. The inherent quality parameters of INAA, such as being virtually free of blank, having fully accountable effects of matrix and physical form, and operating over a huge range of amounts, allows the comparison of a mole (or its fraction) of a pure element with the amount of substance in the sample analyzed with the same direct relationship as a beam balance provides. Indeed, varieties of this approach are in common use in INAA in the comparator methods of quantitation. To eliminate possible perturbations of the traceability chain as they may occur in common INAA practice, experimental measurements have been set up that only involve the fraction of a mole of the element(s) of interest in form of the pure element, compound or certified standard and the unknown sample. This principle has been used in INAA measurements for certification value assignment of high temperature alloy SRMs. To further demonstrate the performance parameters of INAA, we selected the determination of chromium in SRM 1152a Stainless Steel by direct non-destructive comparison with the pure metal in form of crystalline chromium. The measurements were validated with weighed aliquots of SRM 3112a dried on filter paper pellets. The experimental results do not show deviations beyond the uncertainties of the SRMs (≤ 0.2 % relative), and the assessment of the uncertainty budget indicates that expanded uncertainties of ≤ 0.3 % are achievable. The measurements demonstrate that INAA can meet the CCQM definition of a primary ratio method of analysis

  14. INFOMAR, Ireland's National Seabed Mapping Programme; Sharing Valuable Insights.

    Science.gov (United States)

    Judge, M. T.; McGrath, F.; Cullen, S.; Verbruggen, K.

    2017-12-01

    Following the successful high-resolution deep-sea mapping carried out as part of the Irish National Seabed Survey (INSS), a strategic, long term programme was established: INtegrated mapping FOr the sustainable development of Ireland MArine Resources (INFOMAR). Funded by Ireland's Department of Communication, Climate Action and Environment, INFOMAR comprises a multi-platform approach to completing Ireland's marine mapping, and is a key action in the integrated marine plan, Harnessing Our Ocean Wealth. Co-managed by Geological Survey Ireland and the Marine Institute, the programme has three work strands: Data Acquisition; Data Exchange and Integration; Value Added Exploitation.The Data Acquisition strand includes collection of geological, hydrographic, oceanographic, habitat and heritage datasets that underpin sustainable development and management of Ireland's marine resources. INFOMAR operates a free data policy; data and outputs are delivered online through the Data Exchange and Integration strand. Uses of data and outputs are wide-ranging and multipurpose. In order to address the evolution and diversification of user requirements, further data product development is facilitated through the Value Added Exploitation strand.Ninety percent of Ireland's territory lies offshore. Therefore, strategic national seabed mapping continues to provide critical, high-resolution baseline datasets for numerous economic sectors and societal needs. From these we can glean important geodynamic knowledge of Ireland's vast maritime territory. INFOMAR remains aligned with national and European policies and directives. Exemplified by our commitment to EMODnet, a European Commission funded project that supports the collection, standardisation and sharing of available marine information, data and data products across all European Seas. As EMODnet Geology Minerals leaders we have developed a framework for mapping marine minerals. Furthermore, collaboration with the international research

  15. Model of metastatic growth valuable for radionuclide therapy

    International Nuclear Information System (INIS)

    Bernhardt, Peter; Ahlman, Haakan; Forssell-Aronsson, Eva

    2003-01-01

    The aim was to make a Monte Carlo simulation approach to estimate the distribution of tumor sizes and to study the curative potential of three candidate radionuclides for radionuclide therapy: the high-energy electron emitter 90 Y, the medium-energy electron emitter 177 Lu and the low-energy electron emitter 103m Rh. A patient with hepatocellular carcinoma with recently published serial CT data on tumor growth in the liver was used. From these data the growth of the primary tumor, and the metastatis formation rate, were estimated. Assuming the same tumor growth of the primary and all metastases and the same metastatis formation rate from both primary and metastases the metastatic size distribution was simulated for various time points. Tumor cure of the metastatic size distribution was simulated for uniform activity distribution of three radionuclides; the high-energy electron emitter 90 Y, the mean-energy electron emitter 177 Lu and the low-energy electron emitter 103m Rh. The simulation of a tumor cure was performed for various time points and tumor-to-normal tissue activity concentrations, TNC. It was demonstrated that it is important to start therapy as early as possible after diagnosis. It was of crucial importance to use an optimal radionuclide for therapy. These simulations demonstrated that 90 Y was not suitable for systemic radionuclide therapy, due to the low absorbed fraction of the emitted electrons in small tumors ( 103m Rh was slightly better than 177 Lu. For high TNC values low-energy electron emitters, e.g., 103m Rh was the best choice for tumor cure. However, the short half-life of 103m Rh (56 min) might not be optimal for therapy. Therefore, other low-energy electron emitters, or alpha emitters, should be considered for systemic targeted therapy

  16. Parasites as valuable stock markers for fisheries in Australasia, East Asia and the Pacific Islands.

    Science.gov (United States)

    Lester, R J G; Moore, B R

    2015-01-01

    Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.

  17. Therapeutic benefits of enhancing permeability barrier for atopic eczema

    Directory of Open Access Journals (Sweden)

    George Man

    2015-06-01

    Full Text Available The regulatory role of epidermal permeability barrier function in cutaneous inflammation has been well appreciated. While barrier disruption induces cutaneous inflammation, improvement of permeability barrier function alleviates inflammation. Studies have demonstrated that improvement of epidermal permeability barrier function not only prevents the development of atopic eczema, but also delays the relapse of these diseases. Moreover, enhancing the epidermal permeability barrier also alleviates atopic eczema. Furthermore, co-applications of barrier enhancing products with glucocorticoids can increase the therapeutic efficacy and reduce the adverse effects of glucocorticoids in the treatment of atopic eczema. Therefore, utilization of permeability barrier enhancing products alone or in combination with glucocorticoids could be a valuable approach in the treatment of atopic eczema. In this review, we discuss the benefits of improving the epidermal permeability barrier in the management of atopic eczema.

  18. Fluvial archives, a valuable record of vertical crustal deformation

    Science.gov (United States)

    Demoulin, A.; Mather, A.; Whittaker, A.

    2017-06-01

    The study of drainage network response to uplift is important not only for understanding river system dynamics and associated channel properties and fluvial landforms, but also for identifying the nature of crustal deformation and its history. In recent decades, geomorphic analysis of rivers has proved powerful in elucidating the tectonic evolution of actively uplifting and eroding orogens. Here, we review the main recent developments that have improved and expanded qualitative and quantitative information about vertical tectonic motions (the effects of horizontal deformation are not addressed). Channel long profiles have received considerable attention in the literature, and we briefly introduce basic aspects of the behaviour of bedrock rivers from field and numerical modelling perspectives, before describing the various metrics that have been proposed to identify the information on crustal deformation contained within their steady-state characteristics. Then, we review the literature dealing with the transient response of rivers to tectonic perturbation, through the production of knickpoints propagating through the drainage network. Inverse modelling of river profiles for uplift in time and space is also shown to be very effective in reconstructing regional tectonic histories. Finally, we present a synthetic morphometric approach for deducing the tectonic record of fluvial landscapes. As well as the erosional imprint of tectonic forcing, sedimentary deposits, such as fluvial terrace staircases, are also considered as a classical component of tectonic geomorphology. We show that these studies have recently benefited from rapid advances in dating techniques, allowing more reliable reconstruction of incision histories and estimation of incision rates. The combination of progress in the understanding of transient river profiles and larger, more rigorous data sets of terrace ages has led to improved understanding of river erosion and the implications for terrace

  19. Yeast Augmented Network Analysis (YANA: a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk

    Directory of Open Access Journals (Sweden)

    David J. Wiley

    2014-06-01

    Full Text Available Genetic interaction networks that underlie most human diseases are highly complex and poorly defined. Better-defined networks will allow identification of a greater number of therapeutic targets. Here we introduce our Yeast Augmented Network Analysis (YANA approach and test it with the X-linked spinal muscular atrophy (SMA disease gene UBA1. First, we express UBA1 and a mutant variant in fission yeast and use high-throughput methods to identify fission yeast genetic modifiers of UBA1. Second, we analyze available protein-protein interaction network databases in both fission yeast and human to construct UBA1 genetic networks. Third, from these networks we identified potential therapeutic targets for SMA. Finally, we validate one of these targets in a vertebrate (zebrafish SMA model. This study demonstrates the power of combining synthetic and chemical genetics with a simple model system to identify human disease gene networks that can be exploited for treating human diseases.

  20. Systems approach for the selection of micro-RNAs as therapeutic biomarkers of anti-EGFR monoclonal antibody treatment in colorectal cancer

    Science.gov (United States)

    Deyati, Avisek; Bagewadi, Shweta; Senger, Philipp; Hofmann-Apitius, Martin; Novac, Natalia

    2015-01-01

    miRNA plays an important role in tumourgenesis by regulating expression of oncogenes and tumour suppressors. Thus affects cell proliferation and differentiation, apoptosis, invasion and angiogenesis. miRNAs are potential biomarkers for diagnosis, prognosis and therapies of different forms of cancer. However, relationship between response of cancer patients towards targeted therapy and the resulting modifications of the miRNA transcriptome in the context of pathway regulation is poorly understood. With ever-increasing pathways and miRNA-mRNA interaction databases, freely available mRNA and miRNA expression data in multiple cancer therapy have produced an unprecedented opportunity to decipher the role of miRNAs in early prediction of therapeutic efficacy in diseases. Efficient translation of -omics data and accumulated knowledge to clinical decision-making are of paramount scientific and public health interest. Well-structured translational algorithms are needed to bridge the gap from databases to decisions. Herein, we present a novel SMARTmiR algorithm to prospectively predict the role of miRNA as therapeutic biomarker for an anti-EGFR monoclonal antibody i.e. cetuximab treatment in colorectal cancer.

  1. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  2. Towards cheminformatics-based estimation of drug therapeutic index: Predicting the protective index of anticonvulsants using a new quantitative structure-index relationship approach.

    Science.gov (United States)

    Chen, Shangying; Zhang, Peng; Liu, Xin; Qin, Chu; Tao, Lin; Zhang, Cheng; Yang, Sheng Yong; Chen, Yu Zong; Chui, Wai Keung

    2016-06-01

    The overall efficacy and safety profile of a new drug is partially evaluated by the therapeutic index in clinical studies and by the protective index (PI) in preclinical studies. In-silico predictive methods may facilitate the assessment of these indicators. Although QSAR and QSTR models can be used for predicting PI, their predictive capability has not been evaluated. To test this capability, we developed QSAR and QSTR models for predicting the activity and toxicity of anticonvulsants at accuracy levels above the literature-reported threshold (LT) of good QSAR models as tested by both the internal 5-fold cross validation and external validation method. These models showed significantly compromised PI predictive capability due to the cumulative errors of the QSAR and QSTR models. Therefore, in this investigation a new quantitative structure-index relationship (QSIR) model was devised and it showed improved PI predictive capability that superseded the LT of good QSAR models. The QSAR, QSTR and QSIR models were developed using support vector regression (SVR) method with the parameters optimized by using the greedy search method. The molecular descriptors relevant to the prediction of anticonvulsant activities, toxicities and PIs were analyzed by a recursive feature elimination method. The selected molecular descriptors are primarily associated with the drug-like, pharmacological and toxicological features and those used in the published anticonvulsant QSAR and QSTR models. This study suggested that QSIR is useful for estimating the therapeutic index of drug candidates. Copyright © 2016. Published by Elsevier Inc.

  3. A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase.

    Science.gov (United States)

    Wu, Shao Ping; Fu, Ai Ling; Wang, Yu Xia; Yu, Lei Ping; Jia, Pei Yuan; Li, Qian; Jin, Guo Zhang; Sun, Man Ji

    2006-07-21

    The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61 kD was successfully transduced (1 microM) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay. An in vivo experiment in rats showed that the iv administered PTD-TH protein (8 mg/kg) permeated across the blood-brain barrier, penetrated into the striatum and midbrain, and peaked at 5-8 h after the injection. The behavioral effects of PTD-TH on the apomorphine-induced rotations in the PD model rats 8 weeks after the 6-OHDA lesion showed that a single bolus of PTD-TH (8 mg/kg) iv injection caused a decrement of 60% of the contralateral turns on day 1 and 40% on days 5-17. The results imply that iv delivery of PTD-TH is therapeutically effective on the 6-OHDA-induced PD in rats, the PTD-mediated human TH treatment opening a promising therapeutic direction in treatment of PD.

  4. A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase

    International Nuclear Information System (INIS)

    Wu Shaoping; Fu Ailing; Wang Yuxia; Yu Leiping; Jia Peiyuan; Li Qian; Jin Guozhang; Sun Manji

    2006-01-01

    The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61 kD was successfully transduced (1 μM) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay. An in vivo experiment in rats showed that the iv administered PTD-TH protein (8 mg/kg) permeated across the blood-brain barrier, penetrated into the striatum and midbrain, and peaked at 5-8 h after the injection. The behavioral effects of PTD-TH on the apomorphine-induced rotations in the PD model rats 8 weeks after the 6-OHDA lesion showed that a single bolus of PTD-TH (8 mg/kg) iv injection caused a decrement of 60% of the contralateral turns on day 1 and 40% on days 5-17. The results imply that iv delivery of PTD-TH is therapeutically effective on the 6-OHDA-induced PD in rats, the PTD-mediated human TH treatment opening a promising therapeutic direction in treatment of PD

  5. Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia

    Directory of Open Access Journals (Sweden)

    Balasubramanian S

    2014-01-01

    Full Text Available Sivakumar Balasubramanian,1 Aswathy Ravindran Girija,1 Yutaka Nagaoka,1 Seiki Iwai,1 Masashi Suzuki,1 Venugopal Kizhikkilot,2 Yasuhiko Yoshida,1 Toru Maekawa,1 Sakthikumar Dasappan Nair1 1Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan; 2Department of Respiratory Medicine, Sooriya Hospital, Chennai, India Abstract: The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU] and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes by initiating early and late apoptosis. Keywords: nanotechnology, curcumin, 5FU, folate, transferrin, PLGA nanoparticle, magnetic hyperthermia

  6. Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Alireza eFaridar

    2011-12-01

    Full Text Available Therapeutic hypothermia (TH is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS and traumatic brain injury (TBI, however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention.Among the various methods for hypothermia induction, intravascular cooling (IVC may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.

  7. Diagnostic and therapeutic peroral cholangioscopy

    Directory of Open Access Journals (Sweden)

    Jong Ho Moon

    2012-01-01

    Full Text Available Peroral cholangioscopy (POC provides direct visualization of the bile duct and facilitates diagnostic or therapeutic intervention. The currently available single-operator POC systems are "Mother-baby" scope system, SpyGlass direct visualization system, and direct POC using a regular ultra-slim upper endoscope. Direct POC using an ultra-slim upper endoscope having a larger 2-mm working channel can provide a valuable and economic solution for evaluating bile-duct lesions. Main diagnostic procedures under direct POC are visual characterization and optically guided target biopsy for the indeterminate bile duct lesion. Image-enhanced endoscopy such as narrow-band imaging has shown promise for more detailed evaluation of mucosal abnormality and can be performed under direct POC. Intracorporeal lithotripsy such as electrohydraulic lithotripsy or laser lithotripsy is a main therapeutic intervention of direct POC for patients with bile duct stones that are resistant to conventional endoscopic stone-removal procedures. Besides, tumor ablation therapy, such as photodynamic therapy and argon plasma coagulation may be also performed using direct POC. Further developments of the endoscope and specialized accessories or devices are expected to facilitate diagnostic and therapeutic role of this cholangioscopic procedure.

  8. RNAi Therapeutics in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Seunghee Cha

    2013-03-01

    Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

  9. Current diagnostic approach of bone tumors in childhood

    International Nuclear Information System (INIS)

    Torre, Marcia Barbosa; Scatigno Neto, Andre

    1995-01-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs

  10. Valuable Virality

    NARCIS (Netherlands)

    Akpinar, E.; Berger, Jonah

    2017-01-01

    Given recent interest in social media, many brands now create content that they hope consumers will view and share with peers. While some campaigns indeed go “viral,” their value to the brand is limited if they do not boost brand evaluation or increase purchase. Consequently, a key question is how

  11. Valuable Connections

    DEFF Research Database (Denmark)

    Kjærsgaard, Mette Gislev; Smith, Rachel Charlotte

    2014-01-01

    , as well as design, production and use, we might need to rethink the role of ethnography within user centred design and business development. Here the challenge is less about ”getting closer” to user needs and real-life contexts, through familiarization, mediation, and facilitation, and more about creating...... a critical theoretically informed distance from which to perceive and reflect upon complex interconnections between people, technology, business and design, as well as our roles as researchers and designers within these....

  12. Integrated Artificial Intelligence Approaches for Disease Diagnostics.

    Science.gov (United States)

    Vashistha, Rajat; Chhabra, Deepak; Shukla, Pratyoosh

    2018-06-01

    Mechanocomputational techniques in conjunction with artificial intelligence (AI) are revolutionizing the interpretations of the crucial information from the medical data and converting it into optimized and organized information for diagnostics. It is possible due to valuable perfection in artificial intelligence, computer aided diagnostics, virtual assistant, robotic surgery, augmented reality and genome editing (based on AI) technologies. Such techniques are serving as the products for diagnosing emerging microbial or non microbial diseases. This article represents a combinatory approach of using such approaches and providing therapeutic solutions towards utilizing these techniques in disease diagnostics.

  13. Antisense targeting of 3' end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: a new gene-silencing approach.

    Science.gov (United States)

    Marsollier, Anne-Charlotte; Ciszewski, Lukasz; Mariot, Virginie; Popplewell, Linda; Voit, Thomas; Dickson, George; Dumonceaux, Julie

    2016-04-15

    Defects in mRNA 3'end formation have been described to alter transcription termination, transport of the mRNA from the nucleus to the cytoplasm, stability of the mRNA and translation efficiency. Therefore, inhibition of polyadenylation may lead to gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting key 3' end elements involved in mRNA processing using antisense oligonucleotide drugs can be used as a strategy for gene silencing within a potentially therapeutic context. FSHD is a gain-of-function disease characterized by the aberrant expression of the Double homeobox 4 (DUX4) transcription factor leading to altered pathogenic deregulation of multiple genes in muscles. Here, we demonstrate that targeting either the mRNA polyadenylation signal and/or cleavage site is an efficient strategy to down-regulate DUX4 expression and to decrease the abnormally high-pathological expression of genes downstream of DUX4. We conclude that targeting key functional 3' end elements involved in pre-mRNA to mRNA maturation with antisense drugs can lead to efficient gene silencing and is thus a potentially effective therapeutic strategy for at least FSHD. Moreover, polyadenylation is a crucial step in the maturation of almost all eukaryotic mRNAs, and thus all mRNAs are virtually eligible for this antisense-mediated knockdown strategy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. [Cost-effectiveness of the clinical treatment of Grave's disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach].

    Science.gov (United States)

    Lima, Nicolau; Knobel, Meyer; Camargo, Rosalinda Y; Tomimori, Eduardo; Medeiros-Neto, Geraldo

    2005-08-01

    The aim of the present study was to evaluate a new proposal for increasing compliance to the clinical management of patients with Graves' disease (GD) in a large and public University Hospital. The patients were carefully selected (no previous GD treatment, goiter volume less than 6 mL must be living in the metro area of São Paulo), received medication at no cost, were contacted frequently by the social worker and alerted for the date of consultation and only referred to a single endocrinologist during all phases of treatment. We recruited 229 patients with GD that were initially treated with methimazole (MMI--60 mg q.d) in a single daily dose followed by a combination of MMI (20 mg) plus L-T4 (100 microg) daily for 24 months. Only 83 patients (36.2%) completed the protocol and were subdivided in: Group 1 (n= 34) that were in remission for 3 years after discontinuation of the MMI and Group 2 (n= 49) that presented recurrence of GD between 2 and 36 months without MMI. Predictive factors associated with remission were: decrease of the glandular volume, serum TG< 40 ng/mL and normal TRAb values. We concluded that in spite of a careful protocol planned to increase compliance, more than 60% of patients with GD did not complete the therapeutic trial and were referred for radioiodine treatment. The solution for this low therapeutic success for GD should be the possible identification of factors that would indicate patients that are not inclined to follow a long period of clinical therapy.

  15. Therapy Talk: Analyzing Therapeutic Discourse

    Science.gov (United States)

    Leahy, Margaret M.

    2004-01-01

    Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

  16. Converting environmental risks to benefits by using spent coffee grounds (SCG) as a valuable resource.

    Science.gov (United States)

    Stylianou, Marinos; Agapiou, Agapios; Omirou, Michalis; Vyrides, Ioannis; Ioannides, Ioannis M; Maratheftis, Grivas; Fasoula, Dionysia

    2018-06-02

    Coffee is perhaps one of the most vital ingredients in humans' daily life in modern world. However, this causes the production of million tons of relevant wastes, i.e., plastic cups, aluminum capsules, coffee chaff (silver skin), and spent coffee grounds (SCG), all thrown untreated into landfills. It is estimated that 1 kg of instant coffee generates around 2 kg of wet SCG; a relatively unique organic waste stream, with little to no contamination, separated directly in the source by the coffee shops. The produced waste has been under researchers' microscope as a useful feedstock for a number of promising applications. SCG is considered a valuable, nutrients rich source of bioactive compounds (e.g., phenolics, flavonoids, carotenoids, lipids, chlorogenic and protocatechuic acid, melanoidins, diterpenes, xanthines, vitamin precursors, etc.) and a useful resource material in other processes (e.g., soil improver and compost, heavy metals absorbent, biochar, biodiesel, pellets, cosmetics, food, and deodorization products). This paper aims to provide a holistic approach for the SCG waste management, highlighting a series of processes and applications in environmental solutions, food industry, and agricultural sector. Thus, the latest developments and approaches of SCG waste management are reviewed and discussed.

  17. Up-Regulation of Endothelin Type A Receptor in Human and Rat Radiation Proctitis: Preclinical Therapeutic Approach With Endothelin Receptor Blockade

    International Nuclear Information System (INIS)

    Jullien, Nicolash; Blirando, Karl; Milliat, Fabien; Sabourin, Jean-Christophe; Benderitter, Marc; Francois, Agnes

    2009-01-01

    Purpose: Rectum radiation damage and fibrosis are often associated with radiation therapy of pelvic tumors. The endothelin (ET) system has been implicated in several fibrotic diseases but never studied in the context of gastrointestinal radiation damage. This study assessed modifications in ET type 1 (ET-1), ET type A receptor (ET A ), and ET type B receptor (ET B ) localization and/or expression in irradiated human rectal tissue and in a rat model of delayed colorectal injury. We also evaluated the therapeutic potential of long-term ET receptor blockade. Methods and Materials: Routine histological studies of sections of healthy and radiation-injured human rectum tissue were done; the sections were also immunostained for ET A and ET B receptors. The rat model involved the delivery of 27 Gy in a single dose to the colons and rectums of the animals. The ET-1/ET A /ET B expression and ET A /ET B localization were studied at 10 weeks postexposure. The abilities of bosentan and atrasentan to protect against delayed rectal injury were also investigated. Results: The immunolocalization of ET A and ET B in healthy human rectums was similar to that in rat rectums. However, strong ET A immunostaining was seen in the presence of human radiation proctitis, and increased ET A mRNA levels were seen in the rat following colorectal irradiation. Immunostaining for ET A was also strongly positive in rats in areas of radiation-induced mucosal ulceration, atypia, and fibroproliferation. However, neither bosentan nor atrasentan prevented radiation damage to the rectum when given long term. The only effect seen for atrasentan was an increased number of sclerotic vessel sections in injured tissues. Conclusions: As the result of the overexpression of ET A , radiation exposure deregulates the endothelin system through an 'ET A profile' in the human and rodent rectum. However, therapeutic interventions involving mixed or specific ET A receptor blockade do not prevent radiation damage

  18. Two approaches to the clinical dilemma of treating TTP with therapeutic plasma exchange in patients with a history of anaphylactic reactions to plasma.

    Science.gov (United States)

    Sidhu, Davinder; Snyder, Edward L; Tormey, Christopher A

    2017-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease caused by autoantibody-mediated deficiency in von Willebrand factor (VWF) cleaving protease, ADAMTS-13. The primary acute treatment is therapeutic plasma exchange (TPE). However, some patients can develop allergic/anaphylactic reactions to the replacement (i.e., donor) plasma over time. Two potential treatment strategies for patients with TTP who demonstrate severe allergic reactions to plasma used for exchange were examined. Two patients with TTP exacerbations who developed severe allergic reactions to donor plasma were identified. One patient's TPE was re-initiated with Octaplas, a lot-batched solvent and detergent treated, type-specific, pooled donor plasma product. The other patient was exchanged with primarily albumin, followed by slow incremental exposures to donor plasma to mitigate exposures and allergic risks. Both patients were assessed for anaphylaxis. Both treatment strategies were successful in preventing any further clinically significant allergic/anaphylactic reactions and facilitated both patients' TTP remissions. Based on our experience with two similar patients with TTP exacerbations and history of anaphylactic reactions to plasma during TPE, we have identified two possible treatment protocols to achieve remission in this clinical dilemma. Substituting Octaplas for standard plasma or, alternatively, using albumin with slowly increasing amounts of standard plasma may help to mitigate the risk of further anaphylactic adverse events. J. Clin. Apheresis 32:158-162, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence.

    Science.gov (United States)

    Coller, Janet K; Hutchinson, Mark R

    2012-05-01

    In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Clinical and metabolic evaluation of one-stage, full-mouth, ultrasonic debridement as a therapeutic approach for uncontrolled type 2 diabetic patients with periodontitis.

    Science.gov (United States)

    Cirano, Fabiano Ribeiro; Pera, Claudia; Ueda, Paulo; Casarin, Renato Correa Viana; Ribeiro, Fernanda Vieira; Pimentel, Suzana Peres; Casati, Marcio Zaffalon

    2012-09-01

    To evaluate the therapeutic potential of one-stage, full-mouth, ultrasonic debridement (FMUD) as a treatment for type 2 diabetic patients with generalized severe chronic periodontitis. Sixteen patients diagnosed with generalized severe chronic periodontitis and type 2 diabetes mellitus were allocated to the diabetic group; another 15 subjects with periodontitis but without metabolic disorders were placed in the nondiabetic group. Both groups were treated using the FMUD protocol, a unique 45-minute session of ultrasonic debridement of all sites presenting periodontal disease. Patients were analyzed for the following parameters: plaque and bleeding indices, gingival recession, probing depth, and clinical attachment level. Further, diabetic subjects were assessed using fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) tests. Patients were evaluated at 3 and 6 months for all parameters. ANOVA and the Tukey test were used for data analysis (P periodontal health after treatment. There were no significant differences between the groups for any of the parameters assessed (P > .05). Diabetic subjects treated with FMUD had a clinical response similar to that of nondiabetic subjects at all pocket depths. No adverse effects or medical disturbances were observed in either group during treatment. FPG and HbA1c levels remained unaltered after treatment. Within the limitations of this study, FMUD promoted clinical improvements in patients with type 2 uncontrolled diabetes and generalized severe chronic periodontitis.

  1. An evaluation of Neuro-Physiological Psychotherapy: An integrative therapeutic approach to working with adopted children who have experienced early life trauma.

    Science.gov (United States)

    McCullough, Elaine; Gordon-Jones, Susi; Last, Anna; Vaughan, Jay; Burnell, Alan

    2016-10-01

    Research into the effectiveness of therapeutic interventions for older children who have experienced multiple forms of trauma within the context of their early development is scant. This article explores the effectiveness of Neuro-Physiological Psychotherapy (NPP): a wrap-around multi-disciplinary, neuro-sequential, attachment-focussed intervention for children and families who present with multiple, clinically significant, emotional and behavioural difficulties. In total, 31 young people and their adoptive parents took part in the study. Baseline measures were repeated and parents and children interviewed. An assessment of the parent/child relationship and child attachment was undertaken but not analysed for this article. Analysis of the repeated measures received statistically significant changes in behavioural regulation, metacognitive executive functioning and externalising and internalising difficulties, alongside an improvement in thought and social problems. An analysis of the parent interviews provided positive results in terms of the children's engagement in education, an absence of further mental health diagnosis or involvement in the criminal justice system. Further hypotheses are posited regarding the impact of the treatment and further research into the effectiveness of the model outlined. © The Author(s) 2016.

  2. [Therapeutic touch and anorexia nervosa].

    Science.gov (United States)

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. Copyright © 2016. Published by Elsevier Masson SAS.

  3. Introduction to metabolic genetic engineering for the production of valuable secondary metabolites in in vivo and in vitro plant systems.

    Science.gov (United States)

    Benedito, Vagner A; Modolo, Luzia V

    2014-01-01

    Plants are capable of producing a myriad of chemical compounds. While these compounds serve specific functions in the plant, many have surprising effects on the human body, often with positive action against diseases. These compounds are often difficult to synthesize ex vivo and require the coordinated and compartmentalized action of enzymes in living organisms. However, the amounts produced in whole plants are often small and restricted to single tissues of the plant or even cellular organelles, making their extraction an expensive process. Since most natural products used in therapeutics are specialized, secondary plant metabolites, we provide here an overview of the classification of the main classes of these compounds, with its biochemical pathways and how this information can be used to create efficient in and ex planta production pipelines to generate highly valuable compounds. Metabolic genetic engineering is introduced in light of physiological and genetic methods to enhance production of high-value plant secondary metabolites.

  4. Novel Therapeutic Approaches for the Treatment of Depression and CognitiveDeficits in a Rodent Model of Gulf War Veterans’ Illness

    Science.gov (United States)

    2016-10-01

    solutions to increase cell viability and was removed 15 min prior to imaging. Hippocampal slices (450 m) were cut on a vibrating microtome (Leica...Treatment Approaches for Neurological Morbidities in Gulf War Illness”. Invited Speaker Seminar Series at Department of Pharmacology and Toxicology

  5. Valuable Nutrients and Functional Bioactives in Different Parts of Olive (Olea europaea L.)—A Review

    Science.gov (United States)

    Ghanbari, Rahele; Anwar, Farooq; Alkharfy, Khalid M.; Gilani, Anwarul-Hassan; Saari, Nazamid

    2012-01-01

    The Olive tree (Olea europaea L.), a native of the Mediterranean basin and parts of Asia, is now widely cultivated in many other parts of the world for production of olive oil and table olives. Olive is a rich source of valuable nutrients and bioactives of medicinal and therapeutic interest. Olive fruit contains appreciable concentration, 1–3% of fresh pulp weight, of hydrophilic (phenolic acids, phenolic alchohols, flavonoids and secoiridoids) and lipophilic (cresols) phenolic compounds that are known to possess multiple biological activities such as antioxidant, anticarcinogenic, antiinflammatory, antimicrobial, antihypertensive, antidyslipidemic, cardiotonic, laxative, and antiplatelet. Other important compounds present in olive fruit are pectin, organic acids, and pigments. Virgin olive oil (VOO), extracted mechanically from the fruit, is also very popular for its nutritive and health-promoting potential, especially against cardiovascular disorders due to the presence of high levels of monounsaturates and other valuable minor components such as phenolics, phytosterols, tocopherols, carotenoids, chlorophyll and squalene. The cultivar, area of production, harvest time, and the processing techniques employed are some of the factors shown to influence the composition of olive fruit and olive oil. This review focuses comprehensively on the nutrients and high-value bioactives profile as well as medicinal and functional aspects of different parts of olives and its byproducts. Various factors affecting the composition of this food commodity of medicinal value are also discussed. PMID:22489153

  6. Combination of palladium nanoparticles and tubastatin-A potentiates apoptosis in human breast cancer cells: a novel therapeutic approach for cancer

    Directory of Open Access Journals (Sweden)

    Yuan YG

    2017-09-01

    that there was a strong synergistic interaction between TUB-A and PdNPs in increasing apoptosis in human breast cancer cells. These data provide an important preclinical basis for future clinical trials on this drug combination. This combinatorial treatment increased therapeutic potentials, thereby demonstrating a relevant targeted therapy for breast cancer. Furthermore, we have provided the first evidence for the combinatorial effect and mechanism of toxicity of TUB-A and PdNPs in human breast cancer cells. The novelties of the study were identification of a combination therapy that consists of suitable therapeutic molecules that kill cancer cells and also exploration of two different possible mechanisms involved to reduce chemoresistance in cancer cells. Keywords: tubastatin A, palladium nanoparticles, cell viability, oxidative stress, mitochondrial membrane potential, caspases, apoptosis

  7. Mycobacterium tuberculosis DinG is a structure-specific helicase that unwinds G4 DNA: implications for targeting G4 DNA as a novel therapeutic approach.

    Science.gov (United States)

    Thakur, Roshan Singh; Desingu, Ambika; Basavaraju, Shivakumar; Subramanya, Shreelakshmi; Rao, Desirazu N; Nagaraju, Ganesh

    2014-09-05

    The significance of G-quadruplexes and the helicases that resolve G4 structures in prokaryotes is poorly understood. The Mycobacterium tuberculosis genome is GC-rich and contains >10,000 sequences that have the potential to form G4 structures. In Escherichia coli, RecQ helicase unwinds G4 structures. However, RecQ is absent in M. tuberculosis, and the helicase that participates in G4 resolution in M. tuberculosis is obscure. Here, we show that M. tuberculosis DinG (MtDinG) exhibits high affinity for ssDNA and ssDNA translocation with a 5' → 3' polarity. Interestingly, MtDinG unwinds overhangs, flap structures, and forked duplexes but fails to unwind linear duplex DNA. Our data with DNase I footprinting provide mechanistic insights and suggest that MtDinG is a 5' → 3' polarity helicase. Notably, in contrast to E. coli DinG, MtDinG catalyzes unwinding of replication fork and Holliday junction structures. Strikingly, we find that MtDinG resolves intermolecular G4 structures. These data suggest that MtDinG is a multifunctional structure-specific helicase that unwinds model structures of DNA replication, repair, and recombination as well as G4 structures. We finally demonstrate that promoter sequences of M. tuberculosis PE_PGRS2, mce1R, and moeB1 genes contain G4 structures, implying that G4 structures may regulate gene expression in M. tuberculosis. We discuss these data and implicate targeting G4 structures and DinG helicase in M. tuberculosis could be a novel therapeutic strategy for culminating the infection with this pathogen. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Novel approaches to improve the therapeutic index of head and neck radiotherapy: An analysis of data from the PARSPORT randomised phase III trial

    International Nuclear Information System (INIS)

    Buettner, Florian; Miah, Aisha B.; Gulliford, Sarah L.; Hall, Emma; Harrington, Kevin J.; Webb, Steve; Partridge, Mike; Nutting, Christopher M.

    2012-01-01

    Purpose: Subjective xerostomia is a common side-effect following radiotherapy for the treatment of head-and-neck cancer. Standard mean dose models previously used to model xerostomia only that partially predict the occurrence of xerostomia. Studies in animal models have suggested that there are regional variations in the radiosensitivity of the parotid glands. In this work we tested the hypothesis that this is also true for the human parotid gland. Methods: We present novel dose–response models explicitly taking the spatial distribution of the radiation dose into account. We considered dose to the submandibular gland and other clinical factors and used a variable-selection algorithm to select the best dose–response model. This methodology was applied to 63 head and neck cancer patients and validated using two independent patient cohorts of 19 and 29 patients, respectively. Results: The predictive accuracy of dose–response models improved significantly when including regional variations of radiosensitivity of the parotid glands compared to standard mean-dose models (p = 0.001, t-test). Beneficial dose-pattern analysis demonstrated the importance of minimising dose to the lateral and cranial component of the human parotid gland in order to avoid xerostomia. Furthermore we found an evidence that surgical removal of the sub-mandibular gland significantly increases the risk of radiation-induced xerostomia. Conclusion: Dose–response models which take the shape of the dose-distribution into account predicted xerostomia significantly better than standard mean-dose models. Our novel model could be used to rank potential treatment plans more reliably according to their therapeutic index and may be useful to generate better treatment plans.

  9. A combined modality therapeutic approach to metastatic anal squamous cell carcinoma with systemic chemotherapy and local therapy to sites of disease: case report and review of literature.

    Science.gov (United States)

    Gnanajothy, Rosana; Warren, Graham W; Okun, Sherry; Peterson, Lindsay L

    2016-06-01

    Cases of metastatic anal carcinoma managed with a combination of systemic chemotherapy and local therapies to both solitary sites of metastases and the primary site have been reported in the literature. We present a case of a 55-year-old male with metastatic anal squamous cell carcinoma to the liver treated with induction chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5FU) followed by liver resection and radiation to the anal primary with concurrent 5FU and mitomycin. This approach resulted in control of disease without evidence of recurrence, and no increased toxicities now 19 months from initial diagnosis to time of reporting. This novel approach resulted in a good treatment response as documented by imaging and symptom improvement and a long disease free interval.

  10. Extracorporeal Life Support and New Therapeutic Strategies for Cardiac Arrest Caused by Acute Myocardial Infarction - a Critical Approach for a Critical Condition

    Directory of Open Access Journals (Sweden)

    Benedek Theodora

    2016-10-01

    Full Text Available This review summarizes the most recent developments in providing advanced supportive measures for cardiopulmonary resuscitation, and the results obtained using these new therapies in patients with cardiac arrest caused by acute myocardial infarction (AMI. Also detailed are new approaches such as extracorporeal cardiopulmonary resuscitation (ECPR, intra-arrest percutaneous coronary intervention, or the regional models for systems of care aiming to reduce the critical times from cardiac arrest to initiation of ECPR and coronary revascularization.

  11. Designing clinically valuable telehealth resources: processes to develop a community-based palliative care prototype.

    Science.gov (United States)

    Tieman, Jennifer Joy; Morgan, Deidre Diane; Swetenham, Kate; To, Timothy Hong Man; Currow, David Christopher

    2014-09-04

    Changing population demography and patterns of disease are increasing demands on the health system. Telehealth is seen as providing a mechanism to support community-based care, thus reducing pressure on hospital services and supporting consumer preferences for care in the home. This study examined the processes involved in developing a prototype telehealth intervention to support palliative care patients involved with a palliative care service living in the community. The challenges and considerations in developing the palliative care telehealth prototype were reviewed against the Center for eHealth Research (CeHRes) framework, a telehealth development model. The project activities to develop the prototype were specifically mapped against the model's first four phases: multidisciplinary project management, contextual inquiry, value specification, and design. This project has been developed as part of the Telehealth in the Home: Aged and Palliative Care in South Australia initiative. Significant issues were identified and subsequently addressed during concept and prototype development. The CeHRes approach highlighted the implicit diversity in views and opinions among participants and stakeholders and enabled issues to be considered, resolved, and incorporated during design through continuous engagement. The CeHRes model provided a mechanism that facilitated "better" solutions in the development of the palliative care prototype by addressing the inherent but potentially unrecognized differences in values and beliefs of participants. This collaboration enabled greater interaction and exchange among participants resulting in a more useful and clinically valuable telehealth prototype.

  12. INFORMATION – A VALUABLE ELEMENT IN THE MANAGEMENT SYSTEM OF THE MARKET ECONOMY

    Directory of Open Access Journals (Sweden)

    Ion SARBU

    2015-12-01

    Full Text Available News. The globalization process has been accelerated by the explosion of information technologies entering into the work of social, production and education enterprises. Thus, in terms of systemic approach, the company is not a production of goods or services tailored to market requirements, but is equally an information unit producing knowledge. Purpose. The fundamental feature of these processes is applied once that the primary element of information processing is generated always in the information system, the information processed and interpreted in its final form as a resource of the management system. Methods. The article exposed the theoretical and methodological organization of information system of market relations and the role of information as a valuable element of business processes. Results. In the modern knowledge-based economy, increasing information needs at all levels of economic units that generate the emergence of new information products, enhancement of the productive resource and service information and transporting it by modern computerized channels.Information as a productive resource and service as the raw material for creating an active instrument of scientific management and virtual education in Moldova.

  13. Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology

    Directory of Open Access Journals (Sweden)

    Jiebin Hou

    2018-06-01

    Full Text Available Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb. Merr (DS has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use.Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein–protein interaction (PPI relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model.Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD, were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was

  14. A new therapeutic approach for type 1 diabetes: rationale for GNbAC1 an anti-HERV-W-Env monoclonal antibody.

    Science.gov (United States)

    Curtin, Francois; Bernard, Corinne; Levet, Sandrine; Perron, Hervé; Porchet, Hervé; Médina, Julie; Malpass, Sam; Lloyd, David; Simpson, Richard

    2018-05-10

    We describe a newly identified therapeutic target for type 1 diabetes: an envelope protein of endogenous retroviral origin called Human Endogenous Retrovirus W Envelope (HERV-W-Env). HERV-W-Env was found to be detected in the blood of around 60% of type 1 diabetes (T1D) patients and is expressed in acinar pancreatic cells of 75% of T1D patients at post-mortem examination. Preclinical experiments showed that this protein displays direct cytotoxicity on human β-islet cells. In vivo HERV-W-Env impairs the insulin and glucose metabolism in transgenic mice expressing HERV-W-Env. GNbAC1, an IgG4 monoclonal antibody has been developed to specifically target HERV-W-Env and to neutralize the effect of HERV-W-Env in vitro and in vivo. GNbAC1 is currently in clinical development for multiple sclerosis and more than 300 subjects have been administered with GNbAC1 so far. GNbAC1 is now tested in T1D in the RAINBOW-T1D study: a randomized placebo controlled study with the objective of showing the safety and pharmacodynamics response of GNbAC1 in patients suffering from T1D with a maximum duration of 4 years. GNbAC1 is tested versus placebo at the dose of 6 mg/kg in 60 patients during 6 repeated administrations during 6 months, a 6-month open-label extension will follow. The primary endpoint will assess safety and secondary endpoints the pharmacodynamic responses to GNbAC1. GNbAC1 targeting HERV-W-Env is currently in clinical development in T1D with the first safety and pharmacodynamic study. If the study results are positive, this may open the door to the development of an innovative non-immunomodulatory disease modifying treatment for T1D. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children.

    Science.gov (United States)

    Zhang, Xiao-Lei; McGlothan, Jennifer L; Miry, Omid; Stansfield, Kirstie H; Loth, Meredith K; Stanton, Patric K; Guilarte, Tomás R

    2018-01-01

    Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits. In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling. The objective of this study was to determine if activation of TrkB, the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular release. Rats were chronically exposed to Pb2+ prenatally and postnatally until 50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the hippocampus, a phenomenon indicative of reduced vesicular release probability. Decreased vesicular release probability was confirmed by both mean-variance analysis and direct 2-photon imaging of vesicular release from hippocampal slices of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses. This study demonstrates for the first time that in vivo pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals, pointing to TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children. © The Author 2017. Published by Oxford University Press on behalf of the Society of

  16. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    DEFF Research Database (Denmark)

    Ali, Amjad; Naz, Anam; Soares, Siomar C.

    2015-01-01

    -genome approach; the predicted conserved gene families (1,193) constitute similar to 77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost....... Pan-genome analyses of the global representative H. pylori isolates consisting of 39 complete genomes are presented in this paper. Phylogenetic analyses have revealed close relationships among geographically diverse strains of H. pylori. The conservation among these genomes was further analyzed by pan...

  17. Feasible conversion of solid waste bauxite tailings into highly crystalline 4A zeolite with valuable application

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Dongyang; Wang, Zhendong; Guo, Min [State Key Laboratory of Advanced Metallurgy, University of Science and Technology Beijing, Beijing 100083 (China); Zhang, Mei, E-mail: zhangmei@ustb.edu.cn [State Key Laboratory of Advanced Metallurgy, University of Science and Technology Beijing, Beijing 100083 (China); Liu, Jingbo [The Department of Chemistry, Texas A and M University-Kingsville, Kingsville, TX 78363 (United States); The Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

    2014-11-15

    Highlights: • Concept to convert waste to valuable product is carried out in this study. • An industrially feasible and cost-effective approach was developed and optimized. • Highly crystalline and well-defined zeolite was produced under moderate conditions. • The zeolite derived from the bauxite tailings displayed high ion exchange capacity. • Bauxite tailings have potential application in heavy metal ions adsorbent. - Abstract: Bauxite tailings are a major type of solid wastes generated in the flotation process. The waste by-products caused significant environmental impact. To lessen this hazardous effect from poisonous mine tailings, a feasible and cost-effective solution was conceived and implemented. Our approach focused on reutilization of the bauxite tailings by converting it to 4A zeolite for reuse in diverse applications. Three steps were involved in the bauxite conversion: wet-chemistry, alkali fusion, and crystallization to remove impurities and to prepare porous 4A zeolite. It was found that the cubic 4A zeolite was single phase, in high purity, with high crystallinity and well-defined structure. Importantly, the 4A zeolite displayed maximum calcium ion exchange capacity averaged at 296 mg CaCO{sub 3}/g, comparable to commercially-available zeolite (310 mg CaCO{sub 3}/g) exchange capacity. Base on the optimal synthesis condition, the reaction yield of zeolite 4A from bauxite tailings achieved to about 38.43%, hence, this study will provide a new paradigm for remediation of bauxite tailings, further mitigating the environmental and health care concerns, particularly in the mainland of PR China.

  18. Feasible conversion of solid waste bauxite tailings into highly crystalline 4A zeolite with valuable application

    International Nuclear Information System (INIS)

    Ma, Dongyang; Wang, Zhendong; Guo, Min; Zhang, Mei; Liu, Jingbo

    2014-01-01

    Highlights: • Concept to convert waste to valuable product is carried out in this study. • An industrially feasible and cost-effective approach was developed and optimized. • Highly crystalline and well-defined zeolite was produced under moderate conditions. • The zeolite derived from the bauxite tailings displayed high ion exchange capacity. • Bauxite tailings have potential application in heavy metal ions adsorbent. - Abstract: Bauxite tailings are a major type of solid wastes generated in the flotation process. The waste by-products caused significant environmental impact. To lessen this hazardous effect from poisonous mine tailings, a feasible and cost-effective solution was conceived and implemented. Our approach focused on reutilization of the bauxite tailings by converting it to 4A zeolite for reuse in diverse applications. Three steps were involved in the bauxite conversion: wet-chemistry, alkali fusion, and crystallization to remove impurities and to prepare porous 4A zeolite. It was found that the cubic 4A zeolite was single phase, in high purity, with high crystallinity and well-defined structure. Importantly, the 4A zeolite displayed maximum calcium ion exchange capacity averaged at 296 mg CaCO 3 /g, comparable to commercially-available zeolite (310 mg CaCO 3 /g) exchange capacity. Base on the optimal synthesis condition, the reaction yield of zeolite 4A from bauxite tailings achieved to about 38.43%, hence, this study will provide a new paradigm for remediation of bauxite tailings, further mitigating the environmental and health care concerns, particularly in the mainland of PR China

  19. Potential Therapeutic Uses of p19ARF Mimics in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hann, Stephen R

    2005-01-01

    Since many breast tumors have deregulated c-Myc we hypothesize that an ARF mimic would be a valuable therapeutic agent for breast cancer to inhibit c-Myc-induced transformation/tumorigenesis without...

  20. A case report on inVALUABLE: insect value chain in a circular bioeconomy

    DEFF Research Database (Denmark)

    Heckmann, L.-H.; Andersen, J.L.; Eilenberg, J.

    2018-01-01

    partners span the entire value chain and include entrepreneurs, experts in biology, biotechnology, automation, processing and food tech and safety. This paper provides an overview of the goal, activities and some preliminary results obtained during the first year of the project.......The vision of inVALUABLE is to create a sustainable resource-efficient industry for animal production based on insects. inVALUABLE has focus on the R&D demand for scaling up production of insects in Denmark and assessing the application potential of particularly mealworms. The inVALUABLE consortium...

  1. Pediatric therapeutics and medicine administration in resource-poor settings: a review of barriers and an agenda for interdisciplinary approaches to improving outcomes.

    Science.gov (United States)

    Craig, Sienna R; Adams, Lisa V; Spielberg, Stephen P; Campbell, Benjamin

    2009-12-01

    The lack of affordable, available pediatric drug formulations presents serious global health challenges. This article argues that successful pharmacotherapy for children demands an interdisciplinary approach. There is a need to develop new medicines to address acute and chronic illnesses of children, but also to produce formulations of essential medicines to optimize stability, bioavailability, palatability, cost, accurate dosing and adherence. This, in turn, requires an understanding of the social ecologies in which treatment occurs. Understanding health worker, caregiver and patient practices, limitations, and expectations with regard to medicines is crucial to guiding effective drug development and administration. Using literature on pediatric tuberculosis as a reference, this review highlights sociocultural, pharmacological, and structural barriers that impede the delivery of medicines to children. It serves as a basis for the development of an intensive survey of patient, caregiver, and health care worker understandings of, and preferences for, pediatric formulations in three East African countries.

  2. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Antonella Borrelli

    2018-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC. Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the “Two Hit Theory” to the “Multiple Hit Theory”. However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS. The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first “Achilles’ heel” of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor. Recently, a new isoform of human manganese superoxide dismutase (MnSOD was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel

  3. Changes in quality of life as a result of ketogenic diet therapy: A new approach to assessment with the potential for positive therapeutic effects.

    Science.gov (United States)

    Bruce, Susan; Devlin, Anita; Air, Linda; Cook, Lucy

    2017-01-01

    There are difficulties inherent in measuring Quality of life (QoL) in patients with chronic illness, including agreement on definitions of quality of life and the type of measure used, disease specific or generic. Well validated QoL instruments for epilepsy exist but focus on capturing common themes pertinent to children and families as a group instead of focusing on themes important to individual patients and their families/carers. In addition, it is common for numerous items on these inventories to be left incomplete or responded to with "not applicable" since many of the items are not suitable for children with disabilities and their families. This led us to devise a way to capture individual quality-of-life measures that are linked to parental/carer expectations in families of children undergoing ketogenic diet therapy for epilepsy. As part of our routine clinical assessment, parents/carers were asked to describe what they would like to see happen or change as a result of their child being on ketogenic diet therapy. A simple unstructured form was designed to facilitate the assessment process. Parents were then asked to rate their own QoL against these criteria on a Likert scale of 0-10 prior to commencement of the diet. This assessment was repeated at subsequent visits with parents/carers initially blinded to their original responses. Our assessments indicated that ketogenic diet therapy improves quality of life over a twelve-month period when measured against parental expectations. This ideographic approach has demonstrated changes in parental Qol and parental perceptions of their child's quality of life that would not have been captured by other validated measures. A lengthy questionnaire is avoided and is replaced by a skilled supportive conversation that identifies goals for treatment that are important to parents. This helps parents to reflect on the progress their child makes on the diet by revisiting their previously stated aspirations, and assessing

  4. Diagnostic and therapeutic approach to cholestatic liver disease Abordaje diagnóstico y terapéutico del síndrome colestásico

    Directory of Open Access Journals (Sweden)

    T. Pérez Fernández

    2004-01-01

    Full Text Available When cholestatic liver disease is present, liver ultrasound should be performed to ascertain if cholestasis is extrahepatic or intrahepatiic. If bile ducts appear dilated and the probability of interventional treatment is high, endoscopic retrograde cholagio-pancreatography (ERCP or trans-hepatic cholangiography (THC should be the next step. If the probability of interventional therapeutics is low, cholangio-MRI should be performed. Once bile duct dilation and space occupying lesions are excluded, a work up for intrahepatic cholestasis should be started. Some especific clinical situations may be helpful in the diagnostic strategy. If cholestasis occurs in the elderly, drug-induced cholestatic disease should be suspected, whereas if it occurs in young people with risk factors, cholestatic viral hepatitis is the most likely diagnosis. During the first trimester of pregnancy cholestasis may occur in hiperemesis gravidorum, and in the third trimester of gestation cholestasis of pregnancy should be suspected. A familial history of recurrent cholestasis points to benign recurrent intrahepatic cholestasis. The occurrence of intrahepatic cholestasis in a mid-dle-aged woman is a frequent presentation of primary biliary cirrhosis, whereas primary sclerosing cholangitis should be suspected in young males with inflammatory bowel disease. The presence of vascular spider nevi, ascites, and a history of alcohol abuse should point to alcoholic hepatitis. Neonatal cholestasis syndromes include CMV, toxoplasma and rubinfections or metabolic defects such as cystic fibrosis, α1-antitripsin deficiency, bile acid synthesis defects, or biliary atresia. The treatment of cholestasis should include a management of complications such as pruritus, osteopenia and correction of fat soluble vitamin deficiencies. When hepatocellular failure or portal hypertension-related complications occur, liver transplantation should be considered.Ante la presencia de colestasis, se debe

  5. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Science.gov (United States)

    Dewji, Nazneen N; Singer, S Jonathan; Masliah, Eliezer; Rockenstein, Edward; Kim, Mihyun; Harber, Martha; Horwood, Taylor

    2015-01-01

    β-Amyloid (Aβ) accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD). Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP) and Presenilin (PS), as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  6. Peptides of presenilin-1 bind the amyloid precursor protein ectodomain and offer a novel and specific therapeutic approach to reduce ß-amyloid in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nazneen N Dewji

    Full Text Available β-Amyloid (Aβ accumulation in the brain is widely accepted to be critical to the development of Alzheimer's disease (AD. Current efforts at reducing toxic Aβ40 or 42 have largely focused on modulating γ-secretase activity to produce shorter, less toxic Aβ, while attempting to spare other secretase functions. In this paper we provide data that offer the potential for a new approach for the treatment of AD. The method is based on our previous findings that the production of Aβ from the interaction between the β-amyloid precursor protein (APP and Presenilin (PS, as part of the γ-secretase complex, in cell culture is largely inhibited if the entire water-soluble NH2-terminal domain of PS is first added to the culture. Here we demonstrate that two small, non-overlapping water-soluble peptides from the PS-1 NH2-terminal domain can substantially and specifically inhibit the production of total Aβ as well as Aβ40 and 42 in vitro and in vivo in the brains of APP transgenic mice. These results suggest that the inhibitory activity of the entire amino terminal domain of PS-1 on Aβ production is largely focused in a few smaller sequences within that domain. Using biolayer interferometry and confocal microscopy we provide evidence that peptides effective in reducing Aβ give a strong, specific and biologically relevant binding with the purified ectodomain of APP 695. Finally, we demonstrate that the reduction of Aβ by the peptides does not affect the catalytic activities of β- or γ-secretase, or the level of APP. P4 and P8 are the first reported protein site-specific small peptides to reduce Aβ production in model systems of AD. These peptides and their derivatives offer new potential drug candidates for the treatment of AD.

  7. Predicting Social Anxiety Treatment Outcome based on Therapeutic Email Conversations

    NARCIS (Netherlands)

    Hoogendoorn, M.; Berger, Thomas; Schulz, Ava; Stolz, Timo; Szolovits, Peter

    2016-01-01

    Predicting therapeutic outcome in the mental health domain is of utmost importance to enable therapists to provide the most effective treatment to a patient. Using information from the writings of a patient can potentially be a valuable source of information, especially now that more and more

  8. Bioactive compounds of sea cucumbers and their therapeutic effects

    Science.gov (United States)

    Shi, Shujuan; Feng, Wenjing; Hu, Song; Liang, Shixiu; An, Nina; Mao, Yongjun

    2016-05-01

    Sea cucumbers belong to the Class Holothuroidea of marine invertebrates. They are commercially valuable and prized as a food and folk medicine in Asia. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as vitamins, minerals and amino acids. A number of unique biological and pharmacological activities/properties, including anticancer, anticoagulant/antithrombotic, antimicrobial, antioxidant, antihyperlipidemic, antihyperglycemic, anti-inflammatory, antihypertension and radioprotective, have been ascribed to various compounds isolated from sea cucumbers. The therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives, especially triterpene glycosides, acid mucopolysaccharide, sphingoid bases, glycolipids, fucosylated chondroitin sulfate, polysaccharides, phospholipids, cerebrosides, phosphatidylcholines, and other extracts and hydrolysates. This review highlights the valuable bioactive components as well as the multiple therapeutic properties of sea cucumbers with a view to exploring their potential uses as functional foods and a natural source of new multifunctional drugs.

  9. Cardiovascular Risk Factors After Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-S): a New Effective Therapeutic Approach?

    Science.gov (United States)

    Torres, Antonio; Rubio, Miguel A; Ramos-Leví, Ana M; Sánchez-Pernaute, Andrés

    2017-11-07

    Obesity and its associated comorbidities entail a significantly increased cardiovascular mortality. Therefore, approaching obesity control must include among its aims the reduction of the associated comorbidities and the higher cardiovascular mortality risk and not only weight loss. Many observational studies indicate that bariatric surgery (BS) is associated with a better long-term survival than standard care. Furthermore, in general, these epidemiological studies included patients who underwent gastric bypass (GB), not biliopancreatic diversion/duodenal switch (BPD/DS), so the potential additional benefit of this latter technique remains unknown. In this regard, in theory, derivative techniques are usually associated to a higher rate of long-term improvement of metabolic comorbidities, so their potential impact on cardiovascular morbidity and mortality could be even greater than what has been published up to date. In 2007, our group proposed a simplification of the bariatric technique based on the duodenal switch, which we termed "single anastomosis duodeno-ileal bypass with sleeve gastrectomy" or SADI-S. In this review, and 10 years later, we describe some of the main results of those patients who underwent this procedure, specifically regarding their outcome on metabolic comorbidities and cardiovascular risk. Considering the findings presented in this review, in which a significant improvement of all metabolic comorbidities was observed, we may confidently suggest that SADI-S seems comparable to a BPD/DS procedure in the mid-term outcome. After all, the SADI-S procedure was conceived as a simplified version of the BPD/DS technique and not necessarily intended to maximize the improvement of cardiovascular and metabolic comorbidities, which is already sufficiently optimal. In this regard, in our experience, we have encountered a new satisfactory result, which combines more pros than cons. In fact, as we have seen, after a follow-up of 3 years, the outcomes of

  10. Identification of Factors Determining Market Value of the Most Valuable Football Players

    Directory of Open Access Journals (Sweden)

    Sebastian Majewski

    2016-03-01

    Full Text Available Purpose: The problem of identifying the most important determinants of the market value of football players is quite well described in the literature. There are many works that try to identify these factors. Some of them are focused on variables to make a set complete and others are on models and methods. The aim of this article is to present the variables influencing the valuation and to build an econometric model valuing footballers playing on the forward position, taking into consideration the assumptions of the econometric modelling. Such an approach indicates managers as other sources for obtaining information. Methodology: Econometric models were used to verify the hypothesis formulated in this research. The database was created on the basis of variables presented on the website www.transfermarkt. de that presents the values of the most valuable football players in the world playing on the forward position. The Gretl program was used in the research. Findings: The literature review showed that there are many independent variables having an impact on the value of the player. There are also many different models used to valuate footballers’ performance rights. The results of estimation of models in the research indicated that such factors as Canadian classification points adjusted the market value of the team and dummy variables describing “goodwill” (only for the best players had an impact on the market value of footballers’ performance rights. Limitations/implications: Information about different factors having an impact on football players’ market value could support the investment decision process of football managers. Originality/value: The results were part of a study concerning economics of sport, particularly processes of management of football clubs and valuation of intangible assets.

  11. Recovery of valuable metals from electroplating sludge with reducing additives via vitrification.

    Science.gov (United States)

    Huang, Ruth; Huang, Kuo-Lin; Lin, Zih-Yi; Wang, Jian-Wen; Lin, Chitsan; Kuo, Yi-Ming

    2013-11-15

    In this study, vitrification was applied to treat Ni-Cu electroplating sludge. The sludge was mixed with additives (limestone:cullet = 4:6) and then heated to 1450 °C. The cooled product could be separated into slag and ingot. An atomic absorption spectrometer was used to determine the metal levels of specimens and toxicity characteristic leaching procedure (TCLP) tests, whereas the crystalline and surface characteristics were examined using quantitative X-ray diffraction (XRD) analysis and scanning electron microscopy, respectively. With a glassy structure, the slag was mainly composed of Ca, Si, and Mg. The TCLP results of slags met the Taiwan regulated standards, suggesting that slag can be used for recycling purposes. With the aid of additives, the crystalline phase of slag was transformed form CaMgSiO4 into CsSiO3. The ingots were mainly composed of Ni (563,000-693,800 mg/kg), Cu (79,900-87,400 mg/kg), and Fe (35,000-43,600 mg/kg) (target metals) due the gravity separation during vitrification. At appropriate additives/sludge ratios (>0.2), >95% of target metals gathered in the ingot as a recoverable form (Ni-Fe alloy). The high Ni level of slag suggests that the ingot can be used as the raw materials for smelters or the additives for steel making. Therefore, the vitrification approach of this study is a promising technology to recover valuable metals from Ni-Cu electroplating sludge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Market Orientation within University Schools of Business: Can a Dynamical Systems Viewpoint Applied to a Non-Temporal Data Set Yield Valuable Insights for University Managers?

    Science.gov (United States)

    Cox, John C.; Webster, Robert L.; Hammond, Kevin L.

    2009-01-01

    This study investigates the use of using complexity theory--the study of nonlinear dynamical systems of which chaos and catastrophe theory are subsets--in the analysis of a non temporal data set to derive valuable insights into the functioning of university schools of business. The approach is unusual in that studies of nonlinearity in complex…

  13. El dolor en los neonatos: enfoque diagnóstico y terapéutico Pain in neonate infants: diagnostic and therapeutic approach

    Directory of Open Access Journals (Sweden)

    2000-04-01

    Dermoeyector, el Bioeyector y similares que suministran la droga para la anestesia local o regional mediante el uso de gases comprimidos; la utilización de matrices o microesferas polimerizadas biodegradables que al colocarlas en sitios específicos como los nervios o plexos nerviosos liberan lentamente hasta por varios días la droga analgésica y anestésica, lo que permite el alivio prolongado del dolor; la colocación de parches para la aplicación transdérmica de drogas; la administración transtraqueal de opioides como el fentanil. En conclusión, es necesario concienciar acerca de que los neonatos experimentan dolor; que se tienen bases fisiológicas para evaluarlo y tratarlo y para disminuir su exposición a estímulos nocivos y minimizar los resultados adversos. Finalmente, se recomienda que las intervenciones sean efectivas y seguras en el alivio del dolor y el estrés. Neonate infants suffer unnecessary pain due to the complexity of their evaluation, the lack of training of health professionals, the fear to secondary effects of medications, and the presumption that they do not feel it. However, behavioural and physiologic indicators lead to conclude that neonates do feel pain, the prevention and treatment of which avoid suffering and harmful future effects. It is now known that neonates unadequately treated for pain will present learning difficulties and disorders of conduct, memory, socialization, self regulation and sentiment expression. Pain treatment should include humanized assistance, good techniques, precise instruments, and pharmacologic as well as nonpharmacologic approaches; included in the former are opioids, and in the latter adequate posture, caresses, lullaby, pleasant images, music, tactile stimulation and movement. Presently, active research is taking place in the development of noninvasive analgesic methods. It is necessary to create awareness about pain in neonate infants, its detection, evaluation, prevention and treatment.

  14. Current diagnostic approach of bone tumors in childhood; Abordagem diagnostica atual dos tumores osseos na infancia

    Energy Technology Data Exchange (ETDEWEB)

    Torre, Marcia Barbosa; Scatigno Neto, Andre [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Hospital das Clinicas

    1995-09-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs.

  15. How to utilize Ca²⁺ signals to rejuvenate the repairative phenotype of senescent endothelial progenitor cells in elderly patients affected by cardiovascular diseases: a useful therapeutic support of surgical approach?

    Science.gov (United States)

    Moccia, Francesco; Dragoni, Silvia; Cinelli, Mariapia; Montagnani, Stefania; Amato, Bruno; Rosti, Vittorio; Guerra, Germano; Tanzi, Franco

    2013-01-01

    Endothelial dysfunction or loss is the early event that leads to a host of severe cardiovascular diseases, such as atherosclerosis, hypertension, brain stroke, myocardial infarction, and peripheral artery disease. Ageing is regarded among the most detrimental risk factor for vascular endothelium and predisposes the subject to atheroscleorosis and inflammatory states even in absence of traditional comorbid conditions. Standard treatment to restore blood perfusion through stenotic arteries are surgical or endovascular revascularization. Unfortunately, ageing patients are not the most amenable candidates for such interventions, due to high operative risk or unfavourable vascular involvement. It has recently been suggested that the transplantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) might constitute an alternative and viable therapeutic option for these individuals. Albeit pre-clinical studies demonstrated the feasibility of EPC-based therapy to recapitulate the diseased vasculature of young and healthy animals, clinical studies provided less impressive results in old ischemic human patients. One hurdle associated to this kind of approach is the senescence of autologous EPCs, which are less abundant in peripheral blood and display a reduced pro-angiogenic activity. Conversely, umbilical cord blood (UCB)-derived EPCs are more suitable for cellular therapeutics due to their higher frequency and sensitivity to growth factors, such as vascular endothelial growth factor (VEGF). An increase in intracellular Ca(2+) concentration is central to EPC activation by VEGF. We have recently demonstrated that the Ca(2+) signalling machinery driving the oscillatory Ca(2+) response to this important growth factor is different in UCB-derived EPCs as compared to their peripheral counterparts. In particular, we focussed on the so-called endothelial colony forming cells (ECFCs), which are the only EPC population belonging to the endothelial lineage and able

  16. Bee Pollen: Chemical Composition and Therapeutic Application

    Directory of Open Access Journals (Sweden)

    Katarzyna Komosinska-Vassev

    2015-01-01

    Full Text Available Bee pollen is a valuable apitherapeutic product greatly appreciated by the natural medicine because of its potential medical and nutritional applications. It demonstrates a series of actions such as antifungal, antimicrobial, antiviral, anti-inflammatory, hepatoprotective, anticancer immunostimulating, and local analgesic. Its radical scavenging potential has also been reported. Beneficial properties of bee pollen and the validity for their therapeutic use in various pathological condition have been discussed in this study and with the currently known mechanisms, by which bee pollen modulates burn wound healing process.

  17. Novel extractants with high selectivity for valuable metals in seawater. Calixarene derivatives

    International Nuclear Information System (INIS)

    Kakoi, Takahiko; Goto, Masahiro

    1997-01-01

    Seawater contains various valuable metals such as uranium and lithium. Therefore, attempts are being made to develop highly selective extractants which recognize target metal ions in reclaimed seawater. In this review, we have focused our study on the application of novel cyclic compound calixarene based extractants. A novel host compound calixarene, which is a cyclic compound connecting some phenol rings, is capable of forming several different extractant ring sizes and introducing various kinds of functional groups towards targeting of metal ions in seawater. Therefore, calixarene derivatives are capable of extracting valuable metals such as uranium, alkaline metals, heavy metals, rare earth metals and noble metals selectively by varying structural ring size and functional groups. The novel host compound calixarene has given promising results which line it up as a potential extractant for the separation of valuable metal ions in seawater. (author)

  18. Effect of Acid Dissolution Conditions on Recovery of Valuable Metals from Used Plasma Display Panel Scrap

    Directory of Open Access Journals (Sweden)

    Kim Chan-Mi

    2017-06-01

    Full Text Available The objective of this particular study was to recover valuable metals from waste plasma display panels using high energy ball milling with subsequent acid dissolution. Dissolution of milled (PDP powder was studied in HCl, HNO3, and H2SO4 acidic solutions. The effects of dissolution acid, temperature, time, and PDP scrap powder to acid ratio on the leaching process were investigated and the most favorable conditions were found: (1 valuable metals (In, Ag, Mg were recovered from PDP powder in a mixture of concentrated hydrochloric acid (HCl:H2O = 50:50; (2 the optimal dissolution temperature and time for the valuable metals were found to be 60°C and 30 min, respectively; (3 the ideal PDP scrap powder to acid solution ratio was found to be 1:10. The proposed method was applied to the recovery of magnesium, silver, and indium with satisfactory results.

  19. Conversational evidence in therapeutic dialogue.

    Science.gov (United States)

    Strong, Tom; Busch, Robbie; Couture, Shari

    2008-07-01

    Family therapists' participation in therapeutic dialogue with clients is typically informed by evidence of how such dialogue is developing. In this article, we propose that conversational evidence, the kind that can be empirically analyzed using discourse analyses, be considered a contribution to widening psychotherapy's evidence base. After some preliminaries about what we mean by conversational evidence, we provide a genealogy of evaluative practice in psychotherapy, and examine qualitative evaluation methods for their theoretical compatibilities with social constructionist approaches to family therapy. We then move on to examine the notion of accomplishment in therapeutic dialogue given how such accomplishments can be evaluated using conversation analysis. We conclude by considering a number of research and pedagogical implications we associate with conversational evidence.

  20. Sleep and cognitive dysfunctions. Therapeutic approach

    Directory of Open Access Journals (Sweden)

    M.G. Poluektov

    2014-01-01

    Full Text Available This review focuses on the possible mechanisms of sleep disorders in patients with cognitive impairment (CI of different severity. The interrelation between CI, emotional disorders and insomnia, as well as the dependence of CI severity on the degree of sleep disorders, are discussed. The issues related to treatment of sleep disorders in patients with CI, the advantages and disadvantages of modern somnogenic medications are studied. Recommendations on management of patients with a combination of sleep disorders and CI are provided. Data on the use of Egb 761 to treat CI no dementia and melatonin-based drugs to treat sleep disorders in patients with CI are presented. 

  1. Novel Therapeutic Approaches Toward Treating Prostate Cancer

    Science.gov (United States)

    2013-05-01

    Kinases, Prostate Cancer, AKT inhibition, Mouse, Prostate Stem Cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...Bearss 0, Wierda WG, Gandhi V (2009) Pim kinase inhibitor, 5GI-1776, induces apoptosis in CLL lymphocytes. Blood 114:4150--4157. 27. Grey R, et aL...PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem eel! transplantation and rituximab: a Cancer and Leukemia

  2. [Diagnostic and therapeutic approach of intraabdominal candidiasis].

    Science.gov (United States)

    Montero, A; Gilsanz, F; Maseda, E

    2016-09-01

    Invasive fungal disease is associated to a high mortality rate on critical ill patients. In the last decades an important epidemiological shift has been described. Early diagnosis and treatment are related with a better prognosis. The key factors lie in a set of predictive scores that allow to identify patients that will benefit of early treatment, as well as using diagnosis techniques that are culture independent. New diagnosis approximations are being developed with promising results: in situ hybridisation using PNA-FISH probes, MALDI-TOF MS and rapid nucleic acids detection assays. The use of echinocandin is recommended as antifungal therapy on critical ill patients with candida peritonitis.

  3. Therapeutic Approaches of Botulinum Toxin in Gynecology

    OpenAIRE

    Marius Alexandru Moga; Oana Gabriela Dimienescu; Andreea Bălan; Ioan Scârneciu; Barna Barabaș; Liana Pleș

    2018-01-01

    Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT...

  4. Therapeutic approaches for survivors of disaster.

    Science.gov (United States)

    Austin, L S; Godleski, L S

    1999-12-01

    Common psychiatric responses to disasters include depression, PTSD, generalized anxiety disorder, substance-abuse disorder, and somatization disorder. These symptom complexes may arise because of the various types of trauma experienced, including terror or horror, bereavement, and disruption of lifestyle. Because different types of disaster produce different patterns of trauma, clinical response should address the special characteristics of those affected. Traumatized individuals are typically resistant to seeking treatment, so treatment must be taken to the survivors, at locations within their communities. Most helpful is to train and support mental health workers from the affected communities. Interventions in groups have been found to be effective to promote catharsis, support, and a sense of identification with the group. Special groups to be considered include children, injured victims, people with pre-existing psychiatric histories, and relief workers.

  5. New Therapeutic Approaches in Diabetic Retinopathy

    Science.gov (United States)

    Vaziri, Kamyar; Schwartz, Stephen G.; Relhan, Nidhi; Kishor, Krishna S.; Flynn Jr, Harry W.

    2015-01-01

    Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. PMID:26676668

  6. Tennis elbow: a biomechanical and therapeutic approach.

    Science.gov (United States)

    Schnatz, P; Steiner, C

    1993-07-01

    Lateral epicondylitis, one of the most common lesions of the arm, affects some 50% of tennis players. This condition poses a problem in clinical management because treatment is dependent not only on proper medical therapy but also on correction of the improper on-court biomechanics. The most common flaw is a late contact on the backhand groundstroke, forcing the player to extend the wrist with the extensor muscles. This action predisposes to trauma of the tendon fibers at the lateral epicondyle. Understanding the biomechanics will better prepare the physician to advise the patient and to communicate with a tennis teaching professional to facilitate long-term relief.

  7. Amblyopia: neural basis and therapeutic approaches.

    Science.gov (United States)

    Bretas, Caio César Peixoto; Soriano, Renato Nery

    2016-01-01

    Abnormalities in visual processing caused by visual deprivation or abnormal binocular interaction may induce amblyopia, which is characterized by reduced visual acuity. Occlusion therapy, the conventional treatment, requires special attention as occlusion of the fellow normal eye may reduce its visual acuity and impair binocular vision. Besides recovering visual acuity, some researchers have recommended restoration of stereoacuity and motor fusion and reverse suppression in order to prevent diplopia. Recent studies have documented that the amblyopic visual cortex has a normal complement of cells but reduced spatial resolution and a disordered topographical map. Changes occurring in the late sensitive period selectively impact the parvocellular pathway. Distinct morphophysiologic and psychophysical deficits may demand individualization of therapy, which might provide greater and longer-lasting residual plasticity in some children.

  8. Amblyopia: neural basis and therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Caio César Peixoto Bretas

    Full Text Available ABSTRACT Abnormalities in visual processing caused by visual deprivation or abnormal binocular interaction may induce amblyopia, which is characterized by reduced visual acuity. Occlusion therapy, the conventional treatment, requires special attention as occlusion of the fellow normal eye may reduce its visual acuity and impair binocular vision. Besides recovering visual acuity, some researchers have recommended restoration of stereoacuity and motor fusion and reverse suppression in order to prevent diplopia. Recent studies have documented that the amblyopic visual cortex has a normal complement of cells but reduced spatial resolution and a disordered topographical map. Changes occurring in the late sensitive period selectively impact the parvocellular pathway. Distinct morphophysiologic and psychophysical deficits may demand individualization of therapy, which might provide greater and longer-lasting residual plasticity in some children.

  9. Diagnostic and therapeutic approach of systemic amyloidosis

    NARCIS (Netherlands)

    Hazenberg, BPC; van Gameren, [No Value; Bijzet, J; Jager, PL; van Rijswijk, MH

    Amyloidosis is a group of diseases, all characterised by deposition of protein fibrils with a beta-sheet structure. This structure generates affinity of amyloid for Congo red dye and is resistant to proteolysis. Three types of systemic amyloidosis are important for the clinician: AA (related to

  10. Therapeutic working alliance: From a psychoanalitical to a pantheoretical conception

    Directory of Open Access Journals (Sweden)

    Peter Praper

    2004-05-01

    Full Text Available Although the concept of therapeutic working alliance was rooted in psychoanalysis, today it is more prominent in psychoanalytic psychotherapies than psychoanalysis. It is rather surprising that we cannot find the concept in the Laplanche and Pontalis Dictionary. During the last two decades a growing body of empirical research material on therapeutic working alliance was published, confirming the idea of the alliance as a separate dimension of therapeutic relationship with few recognisable components. The dimension of the therapeutic working alliance was examined in several approaches and proved as one of the most important therapeutic factors, regardless of the approach, and it has finally been accepted as a pantheoretical concept.

  11. Dental therapeutic systems.

    Science.gov (United States)

    Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in

  12. Permanent foresty plots: a potentially valuable teaching resource in undergraduate biology porgrams for the Caribbean

    Science.gov (United States)

    H. Valles; C.M.S. Carrington

    2016-01-01

    There has been a recent proposal to change the way that biology is taught and learned in undergraduate biology programs in the USA so that students develop a better understanding of science and the natural world. Here, we use this new, recommended teaching– learning framework to assert that permanent forestry plots could be a valuable tool to help develop biology...

  13. Using Psychodynamic Interaction as a Valuable Source of Information in Social Research

    DEFF Research Database (Denmark)

    Schmidt, Camilla

    2012-01-01

    This article will address the issue of using understandings of psychodynamic interrelations as a means to grasp how social and cultural dynamics are processed individually and collectively in narratives. I apply the two theoretically distinct concepts of inter- and intrasubjectivity to gain insight...... are valuable sources of information in understanding the process of becoming a social educator....

  14. Recovery of valuable nitrogen compounds from agricultural liquid wastes: potential possibilities, bottlenecks and future technological challenges.

    NARCIS (Netherlands)

    Rulkens, W.H.; Klapwijk, A.; Willers, H.C.

    1998-01-01

    Agricultural liquid livestock wastes are an important potential source of valuable nitrogen-containing compounds such as ammonia and proteins. Large volumetric quantities of these wastes are produced in areas with a high livestock production density. Much technological research has been carried out

  15. A field guide to valuable underwater aquatic plants of the Great Lakes

    Science.gov (United States)

    Schloesser, Donald W.

    1986-01-01

    Underwater plants are a valuable part of the Great Lakes ecosystem, providing food and shelter for aquatic animals. Aquatic plants also help stabilize sediments, thereby reducing shoreline erosion. Annual fall die-offs of underwater plants provide food and shelter for overwintering small aquatic animals such as insects, snails, and freshwater shrimp.

  16. THERAPEUTIC APPROACH OF THE PAINFUL LUMBO-RADICULAR SYNDROME (SDLR IN THE LACU-SĂRAT RESORT AND THE ”SC FIZITER SRL” BRĂILA PHYSICAL REHABILITATION CENTRE

    Directory of Open Access Journals (Sweden)

    Viorica Lefter

    2010-06-01

    Full Text Available The high frequency of painful lumboradicular syndromes (SDLR is visible in the international specialised literature, bearing upon a diversity of specialisations (orthopedics, rheumatology, neurology, brain surgery, internal medicine, physiotherapy, social assistance services. Material and method .The present study took place in the interval 2007-2009 and comprised 2847 clinical cases of various types of painful lumbar syndromes (44. 43% out of a total of 6517 patients admitted in our service during the three years of the study,aiming at identifying differentiated nosological entities, presenting the clinical diagnosis criteria and singling out the treatment methodologies. The study proves that a careful and competent clinical examination as well as the accurate interpretation of paraclinical results may provide diagnosis elements allowing the isolation of various distinct nosological entities out of the totality of painful lumbar syndromes, which are subsequently enumerated establishing the percentual proportion to the 2 947 S.D.L.R. cases, as well as to the methodologies of kinetic approach of these entities. 1. The lumbar disc hernia (the multi- or single-level discogen lumboradicularsyndrome (phase III st. III 34.60%. 2. The ”lumbago” discogen lumbalgic syndrome (phase II 4.66%. 3. The myofascial syndrome 39.5%. 4. The facetal syndrome 1.53%. 5. The post-surgery HDL syndrome 12.85%. 6. The lumbalgic syndrome in generalised filrositis 4.25%. 7. Lumbar pains of other origins. The conclusions andresults of this research topic provide useful information, in view of a more certain diagnosis, accurate therapeutic orientation, adequate guiding of patients towards the suitable therapy, the kinetic approach of these entities, elements which may avoid prolonging the evolution, the useless increase of temporary work incapacity,applying precipitous treatments and patient’s iatrogenisation.

  17. Sustainable production of valuable compound 3-succinoyl-pyridine by genetically engineering Pseudomonas putida using the tobacco waste.

    Science.gov (United States)

    Wang, Weiwei; Xu, Ping; Tang, Hongzhi

    2015-11-17

    Treatment of solid and liquid tobacco wastes with high nicotine content remains a longstanding challenge. Here, we explored an environmentally friendly approach to replace tobacco waste disposal with resource recovery by genetically engineering Pseudomonas putida. The biosynthesis of 3-succinoyl-pyridine (SP), a precursor in the production of hypotensive agents, from the tobacco waste was developed using whole cells of the engineered Pseudomonas strain, S16dspm. Under optimal conditions in fed-batch biotransformation, the final concentrations of product SP reached 9.8 g/L and 8.9 g/L from aqueous nicotine solution and crude suspension of the tobacco waste, respectively. In addition, the crystal compound SP produced from aqueous nicotine of the tobacco waste in batch biotransformation was of high purity and its isolation yield on nicotine was 54.2%. This study shows a promising route for processing environmental wastes as raw materials in order to produce valuable compounds.

  18. Pancreas divisum: Analysis and therapeutic alternatives with a case report

    Directory of Open Access Journals (Sweden)

    Jokić Radoica

    2013-01-01

    Full Text Available Introduction. Pancreas divisum is a relatively common pancreatic duct anatomic variant, firstly described in the 17th century. Case report. We reported a 2-year-old child admitted to the Pediatric Clinic with breathing difficulties and abdominal pains. Examination and X-ray image, showed a vast right hydrothorax containing rusty coloured solution with a high degree of amylase. Ultrasound and computed tomography examination revealed pancreatic polycyclic pseudocysts; following magnetic resonance cholangiopancreatography (MRCP, the diagnosis of pancreas divisum was confirmed. The general condition of the patient worsened, requiring an urgent operation. External drainage of the perforated pancreatic pseudocyst was performed. Following external fistula maturation, a change from external to internal drainage was performed using Roux-en-Y fistulojejunostomy. A 3-year postoperative period was uneventful. Conclusion. Pancreas divisum cases are unique requiring clinical experience, rational approach, and complex multimodal management. MRCP is a valuable diagnostic method. Amongst therapeutic options, outer and internal drainage can be seen as reliable methods. Further investigations are absolutely required to determine practical and appropriate conclusions.

  19. Concept of an integrated waste economy represented on the example of recycling of valuable materials

    Energy Technology Data Exchange (ETDEWEB)

    Wender, H

    1980-08-01

    The historical development of waste elimination is discussed, followed by the waste problem in an environmental discussion, the possibilities of recycling within the framework of a waste industry, and the solution of the waste problem from a waste-economy viewpoint, including the definition of 'waste' and the grouping by types of waste, their amounts and increase rates, composition and valuable materials in community wastes with a review of waste technologies under waste-economy viewpoints. This is followed by a discussion of the sales possibilities for valuable components from mechanical sorting facilities, including used paper, old glass, hard substances, metals, plastics, succeeded by a comparative evaluation method, and the national economy aspect of the waste industry, with the savings effect in raw materials for different branches, effects on raw material reserves, the problem of dependence on imports, waste rates and living standard, and the importance of environmental instruments which are discussed in detail.

  20. Mango (Mangifera indica L.) by-products and their valuable components: a review.

    Science.gov (United States)

    Jahurul, M H A; Zaidul, I S M; Ghafoor, Kashif; Al-Juhaimi, Fahad Y; Nyam, Kar-Lin; Norulaini, N A N; Sahena, F; Mohd Omar, A K

    2015-09-15

    The large amount of waste produced by the food industries causes serious environmental problems and also results in economic losses if not utilized effectively. Different research reports have revealed that food industry by-products can be good sources of potentially valuable bioactive compounds. As such, the mango juice industry uses only the edible portions of the mangoes, and a considerable amount of peels and seeds are discarded as industrial waste. These mango by-products come from the tropical or subtropical fruit processing industries. Mango by-products, especially seeds and peels, are considered to be cheap sources of valuable food and nutraceutical ingredients. The main uses of natural food ingredients derived from mango by-products are presented and discussed, and the mainstream sectors of application for these by-products, such as in the food, pharmaceutical, nutraceutical and cosmetic industries, are highlighted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Oncolytic Viruses: Therapeutics With an Identity Crisis

    Directory of Open Access Journals (Sweden)

    Caroline J. Breitbach

    2016-07-01

    Full Text Available Oncolytic viruses (OV are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a “one-size fits all” approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.

  2. Hypnosis as a Valuable Tool for Surgical Procedures in the Oral and Maxillofacial Area.

    Science.gov (United States)

    Montenegro, Gil; Alves, Luiza; Zaninotto, Ana Luiza; Falcão, Denise Pinheiro; de Amorim, Rivadávio Fernandes Batista

    2017-04-01

    Hypnosis is a valuable tool in the management of patients who undergo surgical procedures in the maxillofacial complex, particularly in reducing and eliminating pain during surgery and aiding patients who have dental fear and are allergic to anesthesia. This case report demonstrates the efficacy of hypnosis in mitigating anxiety, bleeding, and pain during dental surgery without anesthesia during implant placement of tooth 14, the upper left first molar.

  3. The cost of being valuable: predictors of extinction risk in marine invertebrates exploited as luxury seafood

    OpenAIRE

    Purcell, Steven W.; Polidoro, Beth A.; Hamel, Jean-François; Gamboa, Ruth U.; Mercier, Annie

    2014-01-01

    Extinction risk has been linked to biological and anthropogenic variables. Prediction of extinction risk in valuable fauna may not follow mainstream drivers when species are exploited for international markets. We use results from an International Union for Conservation of Nature Red List assessment of extinction risk in all 377 known species of sea cucumber within the order Aspidochirotida, many of which are exploited worldwide as luxury seafood for Asian markets. Extinction risk was primari...

  4. World`s Most Valuable Brand Resonation With Categories of Different Customer Needs

    Directory of Open Access Journals (Sweden)

    Kaspars VIKSNE

    2017-09-01

    Full Text Available One of the key performance indicators of brand success is its value. Brand value is an outcome of brand`s performance in market, and is largely depended from brand`s ability to satisfy certain customer needs. For the greatest success in the world`s market brand should resonate its ability to satisfy some of customer`s most universal needs. In this paper authors strives to find out which of the needs world`s most successful brands are resonating with. Therefore paper goal is to is to determine what customer needs world`s most valuable brands are primarily satisfying. First part of paper authors briefly evaluate Maslow theory of needs. In second part of paper authors identify main challenges of brand valuation, and briefly describe today`s most valuable brands. In third part of paper authors analyzes if resonating certain human need in brand makes it to be more valuable. In last part of paper authors summarizes the main findings and gives recommendations for better marketing practices to other brands whose owners have high market ambitions. In order to attain the paper`s goal, authors will use following research methods: Comparative analysis for comparing brands in different brand rankings; Content analysis for determining what need satisfaction brand advertisements resonate; Data analysis for quantify the results gathered from content analysis

  5. Therapeutic radionuclides: Making the right choice

    International Nuclear Information System (INIS)

    Srivastava, S.C.

    1996-01-01

    Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article

  6. Is Botulinum Toxin Type A a Valuable Adjunct During Femoral Lengthening? A Randomized Trial.

    Science.gov (United States)

    Park, Hoon; Shin, Soowan; Shin, Han Sol; Kim, Hyun Woo; Kim, Dong Wook; Lee, Dong Hoon

    2016-12-01

    Reduced joint ROM and distraction-induced pain are common complaints of patients who have undergone gradual femoral lengthening. Attempts to reduce the effects of lengthening on joint motion have included the use of botulinum toxin to reduce the muscle forces that restrict motion. The benefits of this approach during femoral lengthening, however, have not been conclusively established. We wished to evaluate the effects of botulinum toxin type A (BtX-A) injection in the anterior thigh muscles during femoral distraction osteogenesis on adjacent joint ROM and distraction-induced pain. We asked: (1) Does injection of BtX-A in the quadriceps muscles lead to improved knee and hip motion during femoral lengthening? (2) Does injection of BtX-A reduce pain during femoral lengthening? A single-center, double-blind, randomized placebo-controlled trial was conducted. Forty-four patients (88 femurs) undergoing bilateral femoral lengthening for familial short stature were included in the study. BtX-A (200 IU) was injected intraoperatively in the quadriceps muscles of one thigh. An equal volume of sterile normal saline was injected in the other thigh as a control. Selection of the limb receiving the toxin was randomized. Clinical evaluation included a VAS score for pain measurement, ROM evaluation of the hips and knees, and measurement of thigh circumference. Side-to-side differences were analyzed throughout the entire consolidation phase. No patients were lost to followup, leaving 44 patients (88 femurs). The mean followup was 26 months (range, 14-40 months). The distraction rate and final length of gain were similar between treated and control limbs. A priori power analysis suggested that 44 legs were required in each group to achieve statistical significance of 0.05 with 90% power to detect a 50% difference in treatment effect between treatment and control groups. There were no differences in hip ROM, knee ROM, or maximal thigh circumference between the two lower extremities

  7. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction

    International Nuclear Information System (INIS)

    Francois, S.

    2006-01-01

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  8. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  9. Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

    Science.gov (United States)

    Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

    2007-01-01

    The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

  10. Marketing therapeutic recreation services.

    Science.gov (United States)

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  11. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  12. Therapeutic applications of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baker, W.J.; Datz, F.L.; Beightol, R.W.

    1987-01-01

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  13. Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

    Science.gov (United States)

    Kelly, Cynthia W

    2008-04-01

    To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

  14. The Consortium for the Valuation of Applications Benefits Linked with Earth Science (VALUABLES)

    Science.gov (United States)

    Kuwayama, Y.; Mabee, B.; Wulf Tregar, S.

    2017-12-01

    National and international organizations are placing greater emphasis on the societal and economic benefits that can be derived from applications of Earth observations, yet improvements are needed to connect to the decision processes that produce actions with direct societal benefits. There is a need to substantiate the benefits of Earth science applications in socially and economically meaningful terms in order to demonstrate return on investment and to prioritize investments across data products, modeling capabilities, and information systems. However, methods and techniques for quantifying the value proposition of Earth observations are currently not fully established. Furthermore, it has been challenging to communicate the value of these investments to audiences beyond the Earth science community. The Consortium for the Valuation of Applications Benefits Linked with Earth Science (VALUABLES), a cooperative agreement between Resources for the Future (RFF) and the National Aeronautics and Space Administration (NASA), has the goal of advancing methods for the valuation and communication of the applied benefits linked with Earth observations. The VALUABLES Consortium will focus on three pillars: (a) a research pillar that will apply existing and innovative methods to quantify the socioeconomic benefits of information from Earth observations; (b) a capacity building pillar to catalyze interdisciplinary linkages between Earth scientists and social scientists; and (c) a communications pillar that will convey the value of Earth observations to stakeholders in government, universities, the NGO community, and the interested public. In this presentation, we will describe ongoing and future activities of the VALUABLES Consortium, provide a brief overview of frameworks to quantify the socioeconomic value of Earth observations, and describe how Earth scientists and social scientist can get involved in the Consortium's activities.

  15. Reading Philemon as therapeutic narrative | Jordaan | HTS ...

    African Journals Online (AJOL)

    This article analysed the different narratives implied in Philemon by utilising the narrative therapeutic approach, as developed by Epston and White (1990). A dominant narrative (the harsh treatment of slaves in the early Christian environment) and a challenging narrative (a more humane conduct of slaves) were clearly ...

  16. Activating Processes in the Brand Communication of Valuable Brands on the example of Coca-Cola.

    OpenAIRE

    Pöhler, Marie-Luise

    2017-01-01

    Everyone in the world, from the streets of Paris to the villages in Africa, knows the logo with the white letters that are written on a bright red background. Coca-Cola was introduced in 1886. In that year, only nine glasses of the soda drink were sold per day. So how did the little company from Atlanta become the world’s most valuable and popular soft drink? One of the company’s secrets is its emotional and memorable advertising strategies. Therefore, this thesis explains and analyzes ho...

  17. Determination of commercially valuable characteristics of plant varieties for energetic use during the state examination

    Directory of Open Access Journals (Sweden)

    В. В. Баликіна

    2014-12-01

    Full Text Available The analysis of commercially valuable indices of plant varieties for energetic use was carried out and the necessity to determine energetic indices during the state scientific-and-technical examination is substantiated. In order to explain the requirements for registration of new varieties of energy crops concerning the defi nition of indices of ability for distribution, the collection of species and hybrid forms of willow was used. Factors that prove the economic and environmental advantages of energy willow cultivation for biofuel are specifi ed.

  18. The intrapreneur: A distinct and valuable role to be institutionalized and strategically managed

    DEFF Research Database (Denmark)

    Ashourizadeh, Shayegheh; Schøtt, Thomas

    are distinct from routine employees and somewhat similar to entrepreneurs. Thereby intrapreneurs are a human resource that by developing new activities for their employer and also by creating new jobs is very valuable. – The rate of intrapreneurship among employees is higher in Denmark than in almost all other......, especially in Denmark, to adopt strategies for institutionalization and management of this human resource....... more frequently than routine employees are self-efficacious, opportunity-perceiving, risk-willing and role-modeling starters, have meaningful and autonomous jobs, and are satisfied with their jobs and salary, but also experience more stress in work; and in these job-characteristics intrapreneurs...

  19. Process for the extraction of valuable products from coals, pitches, mineral oils, and the like

    Energy Technology Data Exchange (ETDEWEB)

    1936-06-05

    A process is described for the treating of coke, lignite, peat, etc., and mineral oils with the help of hydrogen or other reducing gases and under pressure to recover valuable hydrocarbons, characterized by the carbonaceous substances and the reducing gas coming together already heated totally or in part at least from 350/sup 0/C to the temperature necessary for the reaction. The substances to be treated becoming extracted in the form of paste or liquid from the reaction chamber and then returned to it and being reacted outside the reaction zone in the presence of the reducing gases at the temperature necessary for the reaction.

  20. Inventory of species and cultivars potentially valuable for forest/biomass production

    Energy Technology Data Exchange (ETDEWEB)

    Lavoie, G

    1981-01-01

    To prepare a guide for experiments in mini-rotation or short rotation forest production, potentially valuable species and cultivars have been inventoried. In this text, 288 species are listed under 31 genera, 27 deciduous and 4 coniferous. This partial inventory was made for the Northern Hemisphere and different climates, ranging from the tropical zone to the cold temperate zone. To be included a species had to satisfy the following conditions: ease of established and rapid juvenile growth. The list of species and cultivars is given in alphabetical order. 55 references.

  1. An environmentally friendly electro-oxidative approach to recover valuable elements from NdFeB magnet waste

    NARCIS (Netherlands)

    Venkatesan, P.; Sun, Z.; Sietsma, J.; Yang, Y.

    2018-01-01

    In this manuscript, we demonstrate a room temperature electrochemical process for efficiently recycling NdFeB magnet waste. First, the magnet waste was completely leached with HCl and then, in-situ electrochemical oxidation was performed to selectively oxidize Fe(II) in the leachate to Fe(III).

  2. A valuable approach to the use of electronic medical data in primary care research: Panning for gold.

    Science.gov (United States)

    Barnett, Stephen; Henderson, Joan; Hodgkins, Adam; Harrison, Christopher; Ghosh, Abhijeet; Dijkmans-Hadley, Bridget; Britt, Helena; Bonney, Andrew

    2017-05-01

    Electronic medical data (EMD) from electronic health records of general practice computer systems have enormous research potential, yet many variables are unreliable. The aim of this study was to compare selected data variables from general practice EMD with a reliable, representative national dataset (Bettering the Evaluation and Care of Health (BEACH)) in order to validate their use for primary care research. EMD variables were compared with encounter data from the nationally representative BEACH program using χ 2 tests and robust 95% confidence intervals to test their validity (measure what they reportedly measure). The variables focused on for this study were patient age, sex, smoking status and medications prescribed at the visit. The EMD sample from six general practices in the Illawarra region of New South Wales, Australia, yielded data on 196,515 patient encounters. Details of 90,553 encounters were recorded in the 2013 BEACH dataset from 924 general practitioners. No significant differences in patient age ( p = 0.36) or sex ( p = 0.39) were found. EMD had a lower rate of current smokers and higher average scripts per visit, but similar prescribing distribution patterns. Validating EMD variables offers avenues for improving primary care delivery and measuring outcomes of care to inform clinical practice and health policy.

  3. Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

    International Nuclear Information System (INIS)

    Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

    2007-01-01

    years. New potential therapeutic agents for OPI poisoning include: glycopyrrolate as anticholinergic; organophosphorous hydrolases, butyrilcholinesterases and sodium bicarbonate which degrade OPI and accelerate AChE reactivation; reversible anticholinesterases for reduction of AChE reinchibition; NMDA antagonist as neuroprotectors. Authors from Maryland have proposed the usage of IL-1 Rp antagonists in acute OPI intoxication, a new, original approach to therapy which deserves to be elucidated. For now pharmaceutical industries do not show satisfying initiative in developing new therapeutic agents and antidotes for OPI poisoning. However, randomized, controlled clinical studies, for the beginning with the agents which are in clinical practice, would elucidate their clinical efficacy, reduce the number of lethal pesticide poisonings in developing countries and provide information of special importance for the army and medical service. (author)

  4. Valuable books from the library of Paul Gore (Identification and/or inventory of sources

    Directory of Open Access Journals (Sweden)

    Maria Danilov

    2013-12-01

    Full Text Available Paul Gore (1875-1927 - an outstanding figure of the socio-political, scientific and cultural life of Bessarabia at the beginning of 20th century, was also known among his contemporaries as a keen collector of old and rare books. Undoubtedly, the most valuable part of the library of Paul Gore consisted of books on the history of Bessarabia. Documents from the National Archives of the Republic of Moldova in Chişinău confirm that he inherited a large part of books from his father Gheorghe Gore (1839-1909. A study of the Paul Gore Fund at the National Archives of Romania in Bucharest gave us a lot of documentary evidence of the destiny of this Bessarabian noble library, which later became a property of the King Ferdinand Fund. However, the fate of its most valuable part - books on the history of Bessarabia, consisted of 651 units of the total number of 6456 volumes - is still unknown.

  5. Deep cleaning of a metallurgical zinc leaching residue and recovery of valuable metals

    Science.gov (United States)

    Xing, Peng; Ma, Bao-zhong; Zeng, Peng; Wang, Cheng-yan; Wang, Ling; Zhang, Yong-lu; Chen, Yong-qiang; Wang, Shuo; Wang, Qiu-yin

    2017-11-01

    Huge quantities of zinc leaching residues (ZLRs) generated from zinc production are dumped continuously around the world and pose a potential environmental threat because of their considerable amounts of entrained heavy metals (mainly lead). Most ZLRs have not been properly treated and the valuable metals in them have not yet been effectively recovered. Herein, the deep cleaning of a ZLR and recovery of valuable metals via a hydrometallurgical route were investigated. The cleaning process consists of two essential stages: acid leaching followed by calcium chloride leaching. The optimum conditions for extracting zinc, copper, and indium by acid leaching were a sulfuric acid concentration of 200 g·L-1, a liquid/solid ratio of 4:1 (mL/g), a leaching time of 2 h, and a temperature of 90°C. For lead and silver extractions, the optimum conditions were a calcium chloride concentration of 400 g·L-1, a pH value of 1.0, a leaching time of 1 h, and a temperature of 30°C. After calcium chloride leaching, silver and lead were extracted out and the lead was finally recovered as electrolytic lead by electrowinning. The anglesite phase, which poses the greatest potential environmental hazard, was removed from the ZLR after deep cleaning, thus reducing the cost of environmental management of ZLRs. The treatment of chlorine and spent electrolyte generated in the process was discussed.

  6. Guidelines for Rational Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  7. Lobster processing by-products as valuable bioresource of marine functional ingredients, nutraceuticals, and pharmaceuticals.

    Science.gov (United States)

    Nguyen, Trung T; Barber, Andrew R; Corbin, Kendall; Zhang, Wei

    2017-01-01

    The worldwide annual production of lobster was 165,367 tons valued over $3.32 billion in 2004, but this figure rose up to 304,000 tons in 2012. Over half the volume of the worldwide lobster production has been processed to meet the rising global demand in diversified lobster products. Lobster processing generates a large amount of by-products (heads, shells, livers, and eggs) which account for 50-70% of the starting material. Continued production of these lobster processing by-products (LPBs) without corresponding process development for efficient utilization has led to disposal issues associated with costs and pollutions. This review presents the promising opportunities to maximize the utilization of LPBs by economic recovery of their valuable components to produce high value-added products. More than 50,000 tons of LPBs are globally generated, which costs lobster processing companies upward of about $7.5 million/year for disposal. This not only presents financial and environmental burdens to the lobster processors but also wastes a valuable bioresource. LPBs are rich in a range of high-value compounds such as proteins, chitin, lipids, minerals, and pigments. Extracts recovered from LPBs have been demonstrated to possess several functionalities and bioactivities, which are useful for numerous applications in water treatment, agriculture, food, nutraceutical, pharmaceutical products, and biomedicine. Although LPBs have been studied for recovery of valuable components, utilization of these materials for the large-scale production is still very limited. Extraction of lobster components using microwave, ultrasonic, and supercritical fluid extraction were found to be promising techniques that could be used for large-scale production. LPBs are rich in high-value compounds that are currently being underutilized. These compounds can be extracted for being used as functional ingredients, nutraceuticals, and pharmaceuticals in a wide range of commercial applications

  8. Professional Regulation: A Potentially Valuable Tool in Responding to “Stem Cell Tourism”

    Directory of Open Access Journals (Sweden)

    Amy Zarzeczny

    2014-09-01

    Full Text Available The growing international market for unproven stem cell-based interventions advertised on a direct-to-consumer basis over the internet (“stem cell tourism” is a source of concern because of the risks it presents to patients as well as their supporters, domestic health care systems, and the stem cell research field. Emerging responses such as public and health provider-focused education and national regulatory efforts are encouraging, but the market continues to grow. Physicians play a number of roles in the stem cell tourism market and, in many jurisdictions, are members of a regulated profession. In this article, we consider the use of professional regulation to address physician involvement in stem cell tourism. Although it is not without its limitations, professional regulation is a potentially valuable tool that can be employed in response to problematic types of physician involvement in the stem cell tourism market.

  9. Resource specialization, customer orientation, and firm performance: an empirical investigation of valuable resources

    DEFF Research Database (Denmark)

    Sørensen, Hans Eibe

    2011-01-01

    This study contributes to the strategic marketing research by empirically investigating the role of customer orientation in explaining how firms leverage their specialized but vulnerable resources. The aim is thus to explore a subset of the means by which resources become valuable to the firm...... – the first criterion for a strategic resource. Hypotheses are developed and tested using CEO questionnaire responses from a sample of manufacturing firms and census accounting data. The results show that there is a strong link between industry-specific resources and return on assets for firms with high...... levels of customer orientation. We also report that firm-specific resources are unrelated to firm performance and that a customer orientation – investigated in isolation, may be detrimental to firm performance. Research and managerial implications are discussed....

  10. Cashew nut shell liquid, a valuable raw material for generating semiconductive polyaniline nanofibers

    Directory of Open Access Journals (Sweden)

    Raiane Valenti Gonçalves

    2018-03-01

    Full Text Available Abstract Cashew nut shell liquid (CNSL is an abundant and renewable by-product of the cashew nut industry. It appears to be a valuable raw material for generating semiconductive polyaniline (PAni nanomaterial with enhanced thermal stability and well-defined nanofiber morphology following a polymerization dispersion process. This study confirms that CNSL acts as a soft template during PAni synthesis, leading to an improvement in the nanofiber aspect. CNSL also improves the thermal stability of the PAni nanomaterial. Moreover, CNSL is an effective surfactant that promotes and stabilizes the dispersion of PAni nanofibers within water, allowing the more ecofriendly preparation of PAni nanomaterial by substituting the commonly used organic solvent with aqueous media. Finally, although CNSL promotes the formation of the conductive emeraldine salt form of PAni, increasing CNSL concentrations appear to plasticize the PAni polymer, leading to reduced electrical conductivity. However, this reduction is not detrimental, and PAni nanofibers remain semiconductive even under high CNSL concentrations.

  11. Recovery of valuable products in liquid effluents from uranium and thorium pilot units

    International Nuclear Information System (INIS)

    Jardim, E.A.; Abrao, A.

    1988-01-01

    IPEN-CNEN/SP has being very active in refining yellowcake to pure ammonium diuranate which is converted to uranium trioxide, uranium dioxide, uranium tetra- and hexafluoride in a sequential way. The technology of the thorium purification and its conversion to nuclear grade products has been a practice since several years as well. For both elements the major waste to be worked is the refinate from the solvent extraction column where uranium and thorium are purified via TBP-varsol in pulsed columns. In this paper the actual processing technology is reviewed with special emphasis on the recovery of valuable products, mainly nitric acid and ammonium nitrate. Distilled nitric acid and the final sulfuric acid as residue are recycle. Ammonium nitrate from the precipitation of uranium diuranate is of good quality, being radioactivity and uranium-free, and recommended to be applied as fertilizer. In conclusion the main effort is to maximise the recycle and reuse of the abovementioned chemicals. (author) [pt

  12. The jet impingement cell: A valuable device for investigating CO{sub 2} corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, Brian; John, Douglas; Bailey, Stuart; De Marco, Roland [Western Australian Corrosion Research Group, School of Applied Chemistry, Curtin University of Technology, GPO Box U1987, Perth WA, 6845 (Australia)

    2004-07-01

    The jet impingement cell (JIC) is a valuable technique for the investigation of carbon dioxide corrosion of steel and its inhibition under high flow conditions or high wall shear stress. Despite the use of the JIC in corrosion testing laboratories not a great deal has been published on the design and calibration of these cells. In the evaluation of corrosion inhibitors, the type of corrosion and relative performance of the inhibitors depends on the metallurgy of the steel used to manufacture electrodes and measure the corrosion rate. This paper covers aspects of cell design and the determination of mass transfer and wall shear stress at electrodes used in the cell. The performance of different generic type corrosion inhibitors and their affect on the type of corrosion (i.e, uniform, pitting and crevice corrosion) is shown and discussed. (authors)

  13. Scala vestibuli insertion in cochlear implantation: a valuable alternative for cases with obstructed scala tympani.

    Science.gov (United States)

    Kiefer, J; Weber, A; Pfennigdorff, T; von Ilberg, C

    2000-01-01

    Insertion of a sufficient number of electrodes is important for a successful use of cochlear implants. We investigated the results of scala vestibuli insertion for cochlear implantation in cases of obstructed scala tympani. In a series of 200 cochlear implantations, scala vestibuli insertion was successfully performed in 4 cases with obstruction of the scala tympani. Etiologies included a temporal bone fracture, severe otosclerosis and malformations of the cochlea. The maximum insertion depth obtained via the scala vestibuli was 30 mm. Postoperative results were comparable to patients in whom conventional scala tympani insertion was performed. No adverse effects related to the site of insertion were observed. Scala vestibuli insertion offers a valuable alternative in cases of obstructed scala tympani that can be employed for a variety of etiologies. Copyright 2000 S. Karger AG, Basel

  14. Assessment of Itakura Distance as a valuable feature for computer-aided classification of sleep stages.

    Science.gov (United States)

    Ebrahimi, F; Mikaili, M; Estrada, E; Nazeran, H

    2007-01-01

    Staging and detection of various states of sleep derived from EEG and other biomedical signals have proven to be very helpful in diagnosis, prognosis and remedy of various sleep related disorders. The time consuming and costly process of visual scoring of sleep stages by a specialist has always motivated researchers to develop an automatic sleep scoring system and the first step toward achieving this task is finding discriminating characteristics (or features) for each stage. A vast variety of these features and methods have been investigated in the sleep literature with different degrees of success. In this study, we investigated the performance of a newly introduced measure: the Itakura Distance (ID), as a similarity measure between EEG and EOG signals. This work demonstrated and further confirmed the outcomes of our previous research that the Itakura Distance serves as a valuable similarity measure to differentiate between different sleep stages.