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Sample records for viable therapeutic approach

  1. Therapeutic approaches to cellulite.

    Science.gov (United States)

    Green, Jeremy B; Cohen, Joel L; Kaufman, Joely; Metelitsa, Andrei I; Kaminer, Michael S

    2015-09-01

    Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution. ©2015 Frontline Medical Communications.

  2. Therapeutic Approaches in CLIPPERS.

    Science.gov (United States)

    Taieb, Guillaume; Allou, Thibaut; Labauge, Pierre

    2017-05-01

    CLIPPERS for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a steroid-sensitive and steroid-dependent brainstem inflammatory disease of unknown origin. Since its first description in 2010, about 60 cases have been reported throughout the world. The mean age at onset is 50 years and men seem to be more frequently affected. In patients without chronic corticosteroid therapy or immunosuppressive agents, the disease had a relapsing remitting course, and the mean annualized relapse rate was 0.5. During attacks, although clinical and radiological improvement after high doses of corticosteroids was systematically observed, patients could display subsequent disability and hindbrain atrophy. Since no progressive course was observed, clinical and radiological sequelae were correlated with previous severe attacks. Therefore, maintaining the disease in remission may prevent the accumulation of disability. In the literature, no relapse occurred when chronic corticosteroid therapy was maintained above 20 mg per day. However, steroids side effects led to propose corticosteroid-sparing therapies. Unfortunately, no controlled therapy studies for CLIPPERS have been performed yet, and no therapeutic recommendations exist. Using the PubMed database, all articles having the following keywords "chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids" and "CLIPPERS" have been analysed. Considering that the mean annual relapse rate was 0.5, and that no relapse occurred when corticosteroid therapy was maintained above 20 mg per day, the therapeutic efficiency of corticosteroid-sparing agents was considered as "probable" when patients had a relapse-free period ≥24 months, in the absence of concomitant corticosteroid therapy. Corticosteroid-sparing agents whose efficiency is "probable" are methotrexate in two cases, cyclophosphamide in one case and hydroxychloroquine in one case. Considering the

  3. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    Although prevention is the ideal goal for genetic disorders, various types of therapeutic management are available. Such management approaches depend on the nature of the defect, how well it is understood at the genetic and bio- chemical levels and the practical feasibility of correction. In some conditions.

  4. Zero based programming: a viable security budgeting approach.

    Science.gov (United States)

    Roll, Frederick G

    2003-01-01

    To get additional dollars or avoid budget cuts or personnel reductions, healthcare security directors should consider a budget approach that best justifies the needs of the department or organization.

  5. Enabling Strategy Formulation by ICT: A Viable Systems Approach

    NARCIS (Netherlands)

    Vriens, D.J.; Achterbergh, J.M.I.M.

    2004-01-01

    In this chapter the role of ICT for competitive intelligence is approached from the perspective of strategy formulation. The authors hold the view that competitive intelligence can be seen as knowledge necessary for the process of strategy formulation. To determine the role of ICT, it is proposed to

  6. 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

  7. ELISA microplate: a viable immunocapture platform over magnetic beads for immunoaffinity-LC-MS/MS quantitation of protein therapeutics?

    Science.gov (United States)

    Yang, Wenchu; Kernstock, Robert; Simmons, Neal; Alak, Ala

    2015-01-01

    Evaluate the performance of ELISA microplates versus commonly used magnetic beads for biological sample cleanup and/or enrichment in immunoaffinity-LC-MS/MS to reduce tedious beads washing procedures and a relatively high assay cost. ELISA microplates were used as immunicapture platform and compared with magnetic beads for sample cleanup for LC-MS/MS quantitation of protein therapeutics. One unmodified and two surface-activated microplates provided comparable linear ranges and sensitivities for a therapeutic protein (mass 78 kDa) using a human serum sample of 100 µl with 1:1 dilution compared with Tosylactivated magnetic beads using 200 µl of human serum without sample dilution. The assays' precision and accuracy were all within acceptable ranges. No nonspecific binding or other selectivity issues were observed. The results suggested an ELISA microplate could be a viable immunocapture platform for immunoaffinity-LC-MS/MS quantitation of protein therapeutics.

  8. 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.

  9. [Current Therapeutic Approaches to Sarcoidosis].

    Science.gov (United States)

    Pizarro, Carmen; Skowasch, Dirk; Grohé, Christian

    2017-01-01

    Sarcoidosis represents a non-caseating, granulomatous disorder of unknown aetiology whose clinical manifestation is heterogeneous and frequently multisystemic. The portion of patients needing systemic treatment varies: though many patients may undergo spontaneous remission, organ-threatening courses demand systemic therapy. Corticosteroids are the first-line treatment option; however, disease´s progression and/or major corticosteroid side effects may require second- and third-line therapeutics. A current stepwise therapeutic algorithm to sarcoidosis that characterizes additive and alternative therapeutic agents is given in the following review. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Molecular approaches for viable bacterial population and transcriptional analyses in a rodent model of dental caries.

    Science.gov (United States)

    Klein, M I; Scott-Anne, K M; Gregoire, S; Rosalen, P L; Koo, H

    2012-10-01

    Culturing methods are the primary approach for microbiological analysis of plaque biofilms in rodent models of dental caries. In this study, we developed strategies for the isolation of DNA and RNA from plaque biofilms formed in vivo to analyse the viable bacterial population and gene expression. Plaque biofilm samples from rats were treated with propidium monoazide to isolate DNA from viable cells, and the purified DNA was used to quantify total bacteria and the Streptococcus mutans population via quantitative polymerase chain reaction (qPCR) and specific primers; the same samples were also analysed by counting colony-forming units (CFU). In parallel, RNA was isolated from plaque-biofilm samples (from the same animals) and used for transcriptional analyses via reverse transcription-qPCR. The viable populations of both S. mutans and total bacteria assessed by qPCR were positively correlated with the CFU data (P  0.8). However, the qPCR data showed higher bacterial cell counts, particularly for total bacteria (vs. CFU). Moreover, S. mutans proportion in the plaque biofilm determined by qPCR analysis showed strong correlation with incidence of smooth-surface caries (P = 0.0022, r = 0.71). The purified RNAs presented high RNA integrity numbers (> 7), which allowed measurement of the expression of genes that are critical for S. mutans virulence (e.g. gtfB and gtfC). Our data show that the viable microbial population and the gene expression can be analysed simultaneously, providing a global assessment of the infectious aspect of dental caries. Our approach could enhance the value of the current rodent model in further understanding the pathophysiology of this disease and facilitating the exploration of novel anti-caries therapies. © 2012 John Wiley & Sons A/S.

  11. [Therapeutic approaches in court-ordered therapy].

    Science.gov (United States)

    Floris, Emmanuelle; De Jésus, Arnaud; Cano, Jean-Philippe; Raymondaud, Séverine; Rouveyrol, Éric; Bouchard, Jean-Pierre

    As is the case with other contexts of mental health treatments, the therapeutic approaches to court-ordered therapy are varied. They are based on the principle of their clinical indication and must be delivered by therapists trained in the specific area. The classic therapeutic approaches are used: medication, psychoanalysis and psychoanalytically inspired therapies, cognitive behavioural therapies, group therapies and body-oriented approach. Copyright © 2017. Published by Elsevier Masson SAS.

  12. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    hemophilia and many storage disor- ders), cell-tissue-organ transplantation. (e.g for many disorders like tyrosinemia and polycystic kidney disease), surgical intervention for genetically-determined congenital malformations and late de- veloping surgically correctable com- plications and gene therapy approaches.

  13. Therapeutic approaches to genetic disorders | Zaghloul | Egyptian ...

    African Journals Online (AJOL)

    Abstract. Although prevention is the ideal goal for genetic disorders, various types of therapeutic management are available. Such management approaches depend on the nature of the defect, how well it is understood at the genetic and biochemical levels and the practical feasibility of correction. In some conditions certain ...

  14. 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'.

  15. Current Therapeutic Approach to Hypertrophic Scars

    Directory of Open Access Journals (Sweden)

    Zrinka Bukvić Mokos

    2017-06-01

    Full Text Available Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs, which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.

  16. Postoperative Ileus: Pathophysiology, Current Therapeutic Approaches.

    Science.gov (United States)

    Stakenborg, N; Gomez-Pinilla, P J; Boeckxstaens, G E

    2017-01-01

    Postoperative ileus, which develops after each abdominal surgical procedure, is an iatrogenic disorder characterized by a transient inhibition of gastrointestinal motility. Its pathophysiology is complex involving pharmacological (opioids, anesthetics), neural, and immune-mediated mechanisms. The early neural phase, triggered by activation of afferent nerves during the surgical procedure, is short lasting compared to the later inflammatory phase. The latter starts after 3-6 h and lasts several days, making it a more interesting target for treatment. Insight into the triggers and immune cells involved is of great importance for the development of new therapeutic strategies. In this chapter, the pathogenesis and the current therapeutic approaches to treat postoperative ileus are discussed.

  17. Novel Approach for Enterocutaneous Fistula Treatment with the Use of Viable Cryopreserved Placental Membrane

    Directory of Open Access Journals (Sweden)

    Frederick Nichols

    2016-01-01

    Full Text Available Enterocutaneous fistulas (ECF are a difficult and costly surgical complication to manage. The standard treatment of nil per os (NPO and total paraenteral nutrition (TPN is not well tolerated by patients. TPN is also known for complications associated with long term central venous catheterization and for high cost of prolonged hospital stay. We present two low output ECF cases successfully treated with viable cryopreserved placental membrane (vCPM placed into the fistula tracts. One patient is a 59-year-old male with a low output ECF from a jejunostomy tube site four weeks after the surgery. The second patient is an 87-year-old male with a low output ECF following a small bowel resection secondary to a strangulated inguinal hernia. He was evaluated on day 41 after surgery. NPO and TPN for several weeks did not resolute the ECF. The fistulae were closed postoperatively in both patients with zero output on the same day after one vCPM application. On day 3 postoperatively both patients were started on clear liquid diets and subsequently advanced to regular diets. The ECF have remained resolved for over 2 months. The use of vCPM is a novel promising approach for treatment of ECF.

  18. Therapeutic approaches for tumor necrosis factor inhibition

    OpenAIRE

    Barbosa, Maria Letícia de Castro; Fumian, Milla Machado; Miranda, Ana Luísa Palhares de; Barreiro, Eliezer J.; Lima, Lídia Moreira

    2011-01-01

    Tumor necrosis factor (TNF) consists of an inflammatory cytokine essential for homeostasis and organism defense. Despite its physiological relevance, both increased biosynthesis and release of TNF lead to the exacerbation of inflammatory and oxidative responses, which are related to the pathogenesis of a host of diseases of an inflammatory, autoimmune and/or infectious nature. In this context, effective therapeutic approaches for the modulation of TNF have been the focus of research efforts. ...

  19. Gene therapy in glaucoma-3: Therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Mohamed Abdel-Monem Soliman Mahdy

    2010-01-01

    Recently, several promising genetic therapeutic approaches had been investigated. Some are either used to stop apoptosis and halt further glaucomatous damage, wound healing modulating effect or long lasting intraocular pressure lowering effects than the conventional commercially available antiglaucoma medications. Method of Literature Search The literature was searched on the Medline database using the PubMed interface. The key words for search were glaucoma, gene therapy, and genetic diagnosis of glaucoma.

  20. [Diagnostic-therapeutic approach for retroperitoneal tumors].

    Science.gov (United States)

    Cariati, A

    1993-12-01

    After a careful review of the Literature, diagnostic and therapeutic strategies for Primary Retroperitoneal Tumours (PRT) are reported. The Author analyzes the experience of the Institute of Clinica Chirurgica "R" (Chief: Prof. E. Tosatti) as well as that of Anatomia Chirurgica (Chief: Prof. E. Cariati),--University of Genoa--in the management of PRT, stressing the importance of preoperative staging for a correct surgical approach.

  1. Growth hormone insensitivity: diagnostic and therapeutic approaches.

    Science.gov (United States)

    Kurtoğlu, S; Hatipoglu, N

    2016-01-01

    Growth hormone resistance defines several genetic (primary) and acquired (secondary) pathologies that result in completely or partially interrupted activity of growth hormone. An archetypal disease of this group is the Laron-type dwarfism caused by mutations in growth hormone receptors. The diagnosis is based on high basal levels of growth hormone, low insulin like growth factor-I (IGF-1) level, unresponsiveness to IGF generation test and genetic testing. Recombinant IGF-1 preparations are used in the treatment In this article, clinical characteristics, diagnosis and therapeutic approaches of the genetic and other diseases leading to growth hormone insensitivity are reviewed.

  2. [Therapeutic approaches using genetically modified cells].

    Science.gov (United States)

    Anliker, Brigitte; Renner, Matthias; Schweizer, Matthias

    2015-11-01

    Medicinal products containing genetically modified cells are, in most cases, classified as gene therapy and cell therapy medicinal products. Although no medicinal product containing genetically modified cells has been licensed in Europe yet, a variety of therapeutic strategies using genetically modified cells are in different stages of clinical development for the treatment of acquired and inherited diseases. In this chapter, several examples of promising approaches are presented, with an emphasis on gene therapy for inherited immunodeficiencies and on tumour immunotherapy with genetically modified T-cells expressing a chimeric antigen receptor or a recombinant T-cell receptor.

  3. Common bile duct lithiasis: therapeutic approach.

    Science.gov (United States)

    Neri, Vincenzo; Ambrosi, Antonio; Fersini, Alberto; Tartaglia, Nicola; Lapolla, Francesco

    2013-01-01

    Treatment of cholecysto-choledocholithiasis has been revisited from the standpoint of either endoscopic or laparoscopic mini invasive approach. A standard diagnostic-therapeutic procedure has not been unanimously defined. Since 1997 to 2011 we have treated 924 patients: 555 gallbladder lithiasis, 276 acute biliary pancreatitis and 93 choledocholithiasis (without pancreatitis). We have compared, by the review of the literature, our results of two stage endoscopic stones removal followed by laparoscopic cholecystectomy versus one stage laparo-endoscopic rendezvous technique/VLC and laparoscopic approach alone. In our experience endoscopic removal of stones have been performed in 82 patients (88.17%); 11 patients (11.82%),not eligible for endoscopic approach, have been submitted to laparotomic therapy. In sum preoperative ERCP/ES with CBD cleaning followed by VLC, not with standing the valid results of laparoscopic approach alone remains the strategy more frequently applied in clinical practice, because the good results. The results of the treatment of CBD lithiasis of sequential laparo-endoscopic approach (two or one stage) and of laparoscopic approach alone are roughly overlappable. Therefore the first has remained the treatment of reference and comparison in all the clinical evaluation of different procedure.

  4. Therapeutic approaches of leptin in Alzheimer's disease.

    Science.gov (United States)

    Carro, Eva M

    2009-11-01

    Novel approaches in the understanding of the neurodegeneration observed in Alzheimer's disease (AD), involving neurochemical as well as biochemical techniques are being developed, opening up new possibilities in the direction of a metabolic degeneration. Indeed, brain lipids are closely involved in amyloid beta-related pathogenic pathways. An important modulator of lipid homeostasis is the pluripotent peptide leptin, which has been shown to reduce amyloid beta levels and tau-related pathological pathways, the major pathological hallmarks of AD. These data suggest that leptin holds promise as a novel therapeutic tool for AD. In this article, with some patent literature we will review here some of the most promising approaches involving leptin to cure and prevent, rather than to treat, AD symptoms.

  5. 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.

  6. Potential therapeutic approaches for Angelman syndrome.

    Science.gov (United States)

    Bi, Xiaoning; Sun, Jiandong; Ji, Angela X; Baudry, Michel

    2016-01-01

    Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of maternally inherited UBE3A, an ubiquitin E3 ligase. Despite recent progress in understanding the mechanism underlying UBE3A imprinting, there is no effective treatment. Further investigation of the roles played by UBE3A in the central nervous system (CNS) is needed for developing effective therapies. This review covers the literature related to genetic classifications of AS, recent discoveries regarding the regulation of UBE3A imprinting, alterations in cell signaling in various brain regions and potential therapeutic approaches. Since a large proportion of AS patients exhibit comorbid autism spectrum disorder (ASD), potential common molecular bases are discussed. Advances in understanding UBE3A imprinting provide a unique opportunity to induce paternal UBE3A expression, thus targeting the syndrome at its 'root.' However, such efforts have yielded less-than-expected rescue effects in AS mouse models, raising the concern that activation of paternal UBE3A after a critical period cannot correct all the CNS defects that developed in a UBE3A-deficient environment. On the other hand, targeting abnormal downstream cell signaling pathways has provided promising rescue effects in preclinical research. Thus, combined reinstatement of paternal UBE3A expression with targeting abnormal signaling pathways should provide better therapeutic effects.

  7. 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

  8. New therapeutic approaches to spinal muscular atrophy.

    Science.gov (United States)

    Lewelt, Aga; Newcomb, Tara M; Swoboda, Kathryn J

    2012-02-01

    Bench to bedside progress has been widely anticipated for a growing number of neurodegenerative disorders. Of these, spinal muscular atrophy (SMA) is perhaps the best poised to capitalize on advances in targeted therapeutics development over the next few years. Several laboratories have achieved compelling success in SMA animal models using sophisticated methods for targeted delivery, repair, or increased expression of the survival motor neuron protein, SMN. The clinical community is actively collaborating to identify, develop, and validate outcome measures and biomarkers in parallel with laboratory efforts. Innovative trial design and synergistic approaches to maximize proactive care in conjunction with treatment with one or more of the promising pharmacologic and biologic therapies currently in the pipeline will maximize our chances to achieve meaningful outcomes for patients. This review highlights recent promising scientific and clinical advances bringing us ever closer to effective treatment(s) for our patients with SMA.

  9. Candida Antifungal Resistance and Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Francisca Vieira

    2017-07-01

    Full Text Available Species from genus Candida are characterized by their opportunistic nature and can trigger several infections, especially in immunocompromised hosts. The emergence of non-albicans Candida species, associated with high morbidity and mortality rates, is largely associated with the mechanisms of resistance, intrinsic or acquired, to the conventionally antifungal agents used. Their understanding is fundamental for the development of effective therapeutic approaches. The diagnosis and treatment of these infections poses to be a real challenge and treatment should be implemented as soon as possible. However, on one hand the empirical use of antifungal agents correlates with increased resistance of non-albicans Candida species, on the other hand the antifungal susceptibility testing acts as an auxiliary for targeted therapy, and it is implicit a reduction in the development of resistant species.

  10. Is radical prostatectomy a viable therapeutic option in clinically locally advanced (cT3) prostate cancer?

    Science.gov (United States)

    Xylinas, Evanguelos; Daché, Arnaud; Rouprêt, Morgan

    2010-12-01

    According to the literature, the current preferred treatment for T3 prostate cancer is a combination of radiotherapy and extended hormone therapy. The preoperative staging based on digital rectal examination results alone now appears obsolete from the investigated series, in which 20% of T3 prostate cancer is over-staged during physical examination. Prostatic magnetic resonance imaging is becoming increasingly necessary to evaluate extraprostatic extension during the preoperative evaluation. European Association of Urology guidelines recommend the use of radical prostatectomy only in selected patients with cT3a who have a PSA cancer control obtained after the implementation of radical prostatectomy is variable from one series to another, with PSA-free survival rates at 5, 10 and 15 years ranging from 45 to 62%, 43 to 51% and 15 to 49%, respectively. The specific survival rates at 5, 10 and 15 years are between 84 and 98%, 84 and 91% and 76 and 84%, respectively. The surgical margins rate varies from 22% to 61% depending on the specific operative technique used and the surgeon's own experience level. Regarding urinary continence, functional outcomes are in line with those of prostatectomy for localized prostate cancer. Upon consideration of erectile dysfunction, the rates are linked with the type of surgery performed, which can at times be fairly extensive. There is no impact on the overall or specific survival rate of neoadjuvant treatments. One of the problems currently depends on the efficacy of early adjuvant treatment after prostatectomy, especially regarding the use of adjuvant external beam radiotherapy. Radical prostatectomy can be considered in selected cases as a viable alternative to the first-line treatment option. However, patients must be counselled that they may undergo complementary treatments during the postoperative course of the disease. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

  11. Therapeutic approaches for tumor necrosis factor inhibition

    Directory of Open Access Journals (Sweden)

    Maria Letícia de Castro Barbosa

    2011-09-01

    Full Text Available Tumor necrosis factor (TNF consists of an inflammatory cytokine essential for homeostasis and organism defense. Despite its physiological relevance, both increased biosynthesis and release of TNF lead to the exacerbation of inflammatory and oxidative responses, which are related to the pathogenesis of a host of diseases of an inflammatory, autoimmune and/or infectious nature. In this context, effective therapeutic approaches for the modulation of TNF have been the focus of research efforts. Approximately one million individuals worldwide have been treated with biotechnological inhibitors of this cytokine, the so-called anti-TNF biopharmaceuticals. However, given the high risk of infection and the limitations related to cost and administration routes, new therapeutic approaches aimed at biological targets that directly or indirectly modulate the production and/or activation of TNF appear promising alternatives for the discovery of new anti-inflammatory and immunomodulatory orally active drugs and are therefore discussed in this paper.O fator de necrose tumoral (do inglês, tumor necrosis factor - TNF consiste em uma citocina inflamatória essencial para a homeostase e defesa do organismo. A despeito de sua relevância fisiológica, o aumento da biossíntese e liberação do TNF conduzem à exacerbação das respostas inflamatória e oxidativa, as quais estão relacionadas à patogênese de várias doenças de natureza inflamatória, auto-imune e/ou infecciosa. A busca por abordagens terapêuticas eficientes na modulação do TNF tem sido alvo de diversos esforços de pesquisa. Aproximadamente um milhão de pessoas ao redor do mundo já foi tratado com inibidores biotecnológicos desta citocina, os chamados biofármacos anti-TNF. Entretanto, em face ao elevado risco de infecções e as limitações relacionadas ao custo e a via de administração, novas abordagens terapêuticas com foco em alvos que modulem, de forma direta ou indireta, a produ

  12. Novel therapeutic approaches to autoimmune demyelinating disorders.

    Science.gov (United States)

    Sanvito, Lara; Constantinescu, Cris S; Gran, Bruno

    2011-01-01

    Multiple Sclerosis (MS) is the most common autoimmune demyelinating disorder in Western countries and can lead to permanent disability. Over the past decades remarkable progress has been made in providing new therapeutic strategies to tackle the burden of the disease. Oral drugs and monoclonal antibodies are the main innovative approaches that have been tested in advanced stage clinical trials. Several new drugs have been shown to be superior to traditional disease modifying treatments (DMTs), in terms of both clinical and imaging outcome measures. Oral drugs have the advantage of offering a convenient route of administration. Recently fingolimod has received approval for the treatment of relapsing remitting (RR)-MS in several countries, becoming the first oral drug available to patients. Whilst the majority of the current studies focus on RR-MS, some trials investigate the primary or secondary progressive subtypes as well as the early forms of the disease aiming at delaying the conversion to clinically definite MS. Overall the future of the treatment options looks promising, although the occurrence of significant adverse events in some instances points to cautious evaluation of risks and benefits. Extension studies for most of the new drugs are under way and will provide evidence on the efficacy and long term effects of the new treatment strategies.

  13. Constipation: Pathophysiology and Current Therapeutic Approaches.

    Science.gov (United States)

    Sharma, Amol; Rao, Satish

    2017-01-01

    Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the

  14. In acceptance we trust? Conceptualising acceptance as a viable approach to NGO security management.

    Science.gov (United States)

    Fast, Larissa A; Freeman, C Faith; O'Neill, Michael; Rowley, Elizabeth

    2013-04-01

    This paper documents current understanding of acceptance as a security management approach and explores issues and challenges non-governmental organisations (NGOs) confront when implementing an acceptance approach to security management. It argues that the failure of organisations to systematise and clearly articulate acceptance as a distinct security management approach and a lack of organisational policies and procedures concerning acceptance hinder its efficacy as a security management approach. The paper identifies key and cross-cutting components of acceptance that are critical to its effective implementation in order to advance a comprehensive and systematic concept of acceptance. The key components of acceptance illustrate how organisational and staff functions affect positively or negatively an organisation's acceptance, and include: an organisation's principles and mission, communications, negotiation, programming, relationships and networks, stakeholder and context analysis, staffing, and image. The paper contends that acceptance is linked not only to good programming, but also to overall organisational management and structures. © 2013 The Author(s). Journal compilation © Overseas Development Institute, 2013.

  15. Teaching Writing within the Disciplines: A Viable Approach for English for Academic Purposes (EAP) Instructors

    Science.gov (United States)

    Leopold, Lisa

    2011-01-01

    This case study of an adjunct-model English for Academic Purposes (EAP) writing course linked to a policy-analysis course describes an effective approach for putting "specificity" into practice in EAP curriculum design. The rationale for interdisciplinary collaboration, the positive learning outcomes from the EAP writing course, the…

  16. Buffer-free therapeutic antibody preparations provide a viable alternative to conventionally buffered solutions: from protein buffer capacity prediction to bioprocess applications.

    Science.gov (United States)

    Bahrenburg, Sven; Karow, Anne R; Garidel, Patrick

    2015-04-01

    Protein therapeutics, including monoclonal antibodies (mAbs), have significant buffering capacity, particularly at concentrations>50 mg/mL. This report addresses pH-related issues critical to adoption of self-buffered monoclonal antibody formulations. We evaluated solution conditions with protein concentrations ranging from 50 to 250 mg/mL. Samples were both buffer-free and conventionally buffered with citrate. Samples were non-isotonic or adjusted for isotonicity with NaCl or trehalose. Studies included accelerated temperature stability tests, shaking stability studies, and pH changes in infusion media as protein concentrate is added. We present averaged buffering slopes of capacity that can be applied to any mAb and present a general method for calculating buffering capacity of buffer-free, highly concentrated antibody liquid formulations. In temperature stability tests, neither buffer-free nor conventionally buffered solution conditions showed significant pH changes. Conventionally buffered solutions showed significantly higher opalescence than buffer-free ones. In general, buffer-free solution conditions showed less aggregation than conventionally buffered solutions. Shaking stability tests showed no differences between buffer-free and conventionally buffered solutions. "In-use" preparation experiments showed that pH in infusion bag medium can rapidly approximate that of self-buffered protein concentrate as concentrate is added. In summary, the buffer capacity of proteins can be predicted and buffer-free therapeutic antibody preparations provide a viable alternative to conventionally buffered solutions. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Mesenteric venous thrombosis: multidisciplinary therapeutic approach

    Directory of Open Access Journals (Sweden)

    Stefano Pieri

    2007-08-01

    Full Text Available Mesenteric venous thrombosis is a particular form of intestinal ischemia related to high mortality. The lack of a characteristic clinical picture often leads to a difficult diagnostic and therapeutic classification. We report the case of a young woman, using estrogenic and progestinic oral therapy, affected by a severe form of mesenteric thrombosis and complicated by segmental post ischemic stenosis of small intestine.

  18. Inflammatory mechanisms in ischemic stroke: therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Kirchgessner Annette

    2009-11-01

    Full Text Available Abstract Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours, complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies.

  19. A simple approach for making a viable, safe, and high-performances lithium-sulfur battery

    Science.gov (United States)

    Carbone, Lorenzo; Coneglian, Thomas; Gobet, Mallory; Munoz, Stephen; Devany, Matthew; Greenbaum, Steve; Hassoun, Jusef

    2018-02-01

    We report an electrolyte with low flammability, based on diethylene glycol dimethyl ether (DEGDME) dissolving lithium bis-trifluoromethane sulfonimidate (LiTFSI), and lithium nitrate (LiNO3) for high-performances lithium/sulfur battery. Self-diffusion coefficients, conductivity, and lithium transport number of the electrolyte are obtained by nuclear magnetic resonance and electrochemical impedance spectroscopy. Interface stability, lithium stripping/deposition ability, and the electrochemical stability window of the electrolyte are determined by voltammetry and impedance spectroscopy. The tests suggest conductivity higher than 10-2 S cm-1, lithium transport number of about 0.5, electrochemical stability extending from 0 V to 4.6 V, and excellent compatibility with lithium metal. A composite cathode using sulfur and multi walled carbon nanotubes (MWCNTs) is characterized in terms of structure and morphology by X-ray diffraction and scanning electron microscopy. The study shows spherical flakes in which the carbon nanotubes protect the crystalline sulfur from excessive dissolution, and create the optimal host for allowing the proper cell operation. The Li/S cell reveals highly reversible process during charge/discharge cycles, fast kinetic, and lithium diffusion coefficient in the sulfur electrode ranging from 10-12 to 10-10 cm2 s-1. The cell evidences a coulombic efficiency approaching 100%, capacity from 1300 mAh g-1 to 900 mAh g-1 and practical energy density higher than 400 Wh kg-1.

  20. Dual Mode Offering As Viable Approach 
For Promotion Of Higher Education In Pakistan

    Directory of Open Access Journals (Sweden)

    Irshad HUSSAIN

    2014-01-01

    Full Text Available Pakistan is a developing with 148 universities and degree awarding institutions including public and private sector. The enrolment as given in the National Educational Policy 2009 was up to 5% only. It reflects greater demands of higher/tertiary education and calls for alternative strategic measures for addressing the issue. An innovative approach was necessary to address the issue of access. Therefore, the Islamia University of Bahawalpur –a formal mode university took an innovative initiative to become a dual mode university by establishing an Institute of Distance Education (IDE in 2011. The institute offered along with others, an M.Phill programme in ten disciplines through distance education mode in semester fall 2011. More than eight hundred applications were received by potential learners against 275 seats. However, after test and interview 189 students were enrolled in M.Phill programme in Applied Psychology, Arabic, Education, English, Media Studies, Islamic Studies, Pakistan Studies, History, Persian, and Urdu. In the beginning, the Institute organized an orientation workshop for learners to guide them studying in distance education system. The programme was offered under semester system and the semester was broke up into two halves –mid-term and final term. The respective departments provided learning materials to students whereas the IDE provided instructional booklet. Submission of two assignments was compulsory for the entire semester; one before mid-term and second before final-term workshop/ examination for each of the courses. Similarly, students’ presence in workshops for 24 hours (12 during mid-term and 12 during final-term workshop for one 3-credit hour course was mandatory. Students’ support services were provided through Skype conference, social media and mobile phones. Students necessarily had to give presentations and submit their assignments after checking their similarity index by using turnitin software. At the

  1. DUAL MODE OFFERING AS VIABLE APPROACH FOR PROMOTION OF HIGHER EDUCATION IN PAKISTAN

    Directory of Open Access Journals (Sweden)

    Irshad HUSSAIN

    2014-07-01

    Full Text Available Pakistan is a developing with 148 universities and degree awarding institutions including public and private sector. The enrolment as given in the National Educational Policy 2009 was up to 5% only. It reflects greater demands of higher/tertiary education and calls for alternative strategic measures for addressing the issue. An innovative approach was necessary to address the issue of access. Therefore, the Islamia University of Bahawalpur –a formal mode university took an innovative initiative to become a dual mode university by establishing an Institute of Distance Education (IDE in 2011. The institute offered along with others, an M.Phill programme in ten disciplines through distance education mode in semester fall 2011. More than eight hundred applications were received by potential learners against 275 seats. However, after test and interview 189 students were enrolled in M.Phill programme in Applied Psychology, Arabic, Education, English, Media Studies, Islamic Studies, Pakistan Studies, History, Persian, and Urdu. In the beginning, the Institute organized an orientation workshop for learners to guide them studying in distance education system. The programme was offered under semester system and the semester was broke up into two halves –mid-term and final term. The respective departments provided learning materials to students whereas the IDE provided instructional booklet. Submission of two assignments was compulsory for the entire semester; one before mid-term and second before final-term workshop/ examination for each of the courses. Similarly, students’ presence in workshops for 24 hours (12 during mid-term and 12 during final-term workshop for one 3-credit hour course was mandatory. Students’ support services were provided through Skype conference, social media and mobile phones. Students necessarily had to give presentations and submit their assignments after checking their similarity index by using turnitin software. At the

  2. 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.

  3. Pediatric Tandem Therapeutic Apheresis: A Multidisciplinary Approach.

    Science.gov (United States)

    Sirignano, Rachel M; Meyer, Erin K; Fasano, Ross; Paden, Matthew L

    2017-08-31

    The epidemiology, safety, and efficacy of pediatric multiple tandem extracorporeal therapies are not well understood. We conducted a retrospective chart review of therapeutic apheresis (TA) from January 1, 2012 to October 31, 2015. We collected procedural/clinical demographics, American Society for Apheresis (ASFA) indication, complications, and mortality. One hundred eighty tandem TA procedures were performed in 53 patients. Median age was 9 years (range: 2 months to 21 years) with a median weight of 28 kg (range: 6-170.3 kg) with nine patients weighing download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  4. Novel bioequivalence approach for narrow therapeutic index drugs.

    Science.gov (United States)

    Yu, L X; Jiang, W; Zhang, X; Lionberger, R; Makhlouf, F; Schuirmann, D J; Muldowney, L; Chen, M-L; Davit, B; Conner, D; Woodcock, J

    2015-03-01

    Narrow therapeutic index drugs are defined as those drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity. The US Food and Drug Administration proposes that the bioequivalence of narrow therapeutic index drugs be determined using a scaling approach with a four-way, fully replicated, crossover design study in healthy subjects that permits the simultaneous equivalence comparison of the mean and within-subject variability of the test and reference products. The proposed bioequivalence limits for narrow therapeutic index drugs of 90.00%-111.11% would be scaled based on the within-subject variability of the reference product. The proposed study design and data analysis should provide greater assurance of therapeutic equivalence of narrow therapeutic index drug products. © 2014 American Society for Clinical Pharmacology and Therapeutics.

  5. Recent novel tumor gatekeepers and potential therapeutic approaches

    African Journals Online (AJOL)

    ... have been made to present some of the latest knowledge about novel tumor gatekeepers and new therapeutic strategies to improve the efficacy of chemotherapy and give new hope to cancer patients to fight against cancer. Keywords: Cancer, Potent inhibitors, Gatekeepers, Therapeutic approaches, Oncogenic pathways ...

  6. Nanotechnology based approaches in cancer therapeutics

    Science.gov (United States)

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

    2014-12-01

    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.

  7. Holistic approach to production systems from the perspective of lean manufacturing and viable systems model; Aproximacion holistica a los sistemas de produccion desde la perspectiva Lean Manufacturing y Modelos de Sistemas Viables

    Energy Technology Data Exchange (ETDEWEB)

    Puche Regaliza, J. C.; Costas Gual, J.

    2012-07-01

    The reductionism approach usually adopted by many organizations provokes too often a problem of sustain ability in the market over time in these organizations. To increase this sustain ability, we propose a structural and a behavioral change, in a way that the reductionism is replaced by an holistic approach appropriate to address the dynamic complexity inherent in any organization. With regard to structural change, we propose the use of Organizational Cybernetics and particularly the Viable System Model. With respect to behavior change, we propose the use of Lean Manufacturing paradigm. (Author)

  8. Novel Therapeutic Approach for Breast Cancer

    Science.gov (United States)

    2006-06-01

    64] Liu, X.; Kim, C.N.; Yang, J.; Jemmerson, R.; Wang, X. Cell, 1996, 86, 147. [65] Susin, S.A.; Lorenzo , H.K.; Zamzami, N.; Marzo, I.; Snow, B.E...L.; Sarkar, D.; Z., S.Z.; Lebedeva, I.; Dent, P.; Mahas- reshti, P.J.; Curiel, D.T.; Fisher, P.B. 96th AACR Annual Meeting, 2005, San Diego, CA. [87...promoter to drive the E4 gene (Ad2Xtyr) and the efficacy of this approach was demonstrated in in vitro organotypic raft cultures.40 In a similar approach

  9. [Biliary lithiasis in childhood: therapeutic approaches].

    Science.gov (United States)

    Escobar Castro, H; García Novo, Ma D; Olivares, P

    2004-02-01

    Until recently, biliary lithiasis was considered infrequent in childhood. According to their composition, gallstones can be classified into cholesterol stones and pigment stones. The latter are mainly composed of calcium salts of unconjugated bilirubin and are divided into hard black and soft brown stones. In children, up to 75 % of gallstones are pigment stones. Their etiology is often unknown. Biliary lithiasis in children differs from that in adults and there is very little scientific evidence on the most suitable therapeutic procedures. Symptom-free stones usually have a benign course and do not require medical or surgical treatment. Symptoms are often nonspecific and include dyspepsia and chronic abdominal pain. These symptoms are an indication for ultrasonographic scan to rule out the presence of gallstones. Cholecystectomy is the definitive treatment for gallstones but is not always indicated. Medical treatment with ursodeoxycholic acid is indicated in oligosymptomatic and asymptomatic lithiasis with transparent, soft, cholesterol-rich stones and a functional bladder and in patients with a high surgical risk.

  10. 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.

  11. 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.

  12. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    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. Current therapeutic approaches for plantar fasciitis

    Directory of Open Access Journals (Sweden)

    Martinelli N

    2014-03-01

    Full Text Available Nicolò Martinelli, Carlo Bonifacini, Giovanni RomeoDepartment of Ankle and Foot Surgery, IRCCS Galeazzi Orthopaedic Institute, Milan, ItalyAbstract: Almost 1 million Americans are affected by plantar fasciitis (PF, which is the commonest cause of chronic heel pain. This condition is often managed conservatively, and many rehabilitation protocols, some with the aid of orthoses, have been adopted, with good-to-excellent clinical results. Although most cases of chronic PF can be successfully managed with a conservative approach, alternative treatments, including high-energy shock wave therapy and corticosteroid injections, are commonly accepted as second-line treatment when traditional conservative therapy fails. However, surgery is still an important mode of treatment. Recently, new minimally invasive surgical techniques that offer numerous advantages (faster recovery time, early weight-bearing, lower postoperative pain over standard surgical approaches have been proposed, with good results and low complication rates. The purpose of this review is to report new conservative and surgical techniques for the treatment of PF. A literature search for articles about plantar fasciitis was conducted on the PubMed database in order to identify publications addressing the treatments of PF. The literature suggests that, initially, traditional conservative treatments consisting of rest, oral nonsteroidal anti-inflammatory drugs, foot orthotics, and stretching exercises can be tried for several weeks. In patients with chronic recalcitrant PF, extracorporeal shock wave therapy or corticosteroid injection can be considered. Surgery (minimally invasive techniques should be considered only after failure of the conservative treatments.Keywords: heel pain, surgery, plantar fasciosis

  14. A therapeutic approach for senile dementias: neuroangiogenesis.

    Science.gov (United States)

    Ambrose, Charles T

    2015-01-01

    Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing medical and economic crisis in this country. Apart from cautioning persons about risk factors, no practical, effective therapy is currently available. Much of the recent research in AD has been based on the amyloid cascade theory. Another approach assumes a vascular basis for SDs. This paper presents evidence from a score of studies that cerebral capillary density (CCD) declines during old age in animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and maintain capillaries in the brain. Thus a waning level of these factors and the ensuing declining CCD would lead to local areas of reduced oxygen and glucose and result in impaired synaptic and neuronal function. The NAG hypothesis developed here proposes that the age-linked decline in CCD is a terminal condition in SDs, including many cases of AD. This age-linked decline is independent of any other of the various pathologies proposed as causing AD and listed in Table 1. Waning NAG factors would render the SDs a deficiency condition, somewhat like falling androgen levels in aging males. A logical corollary of this hypothesis is that chronic replacement therapy with recombinant forms of NAG factors may arrest the age-linked decline in CCD and prevent further loss of memory and mental deterioration. A transnasal route of therapy seems the most practical one for general use in the large aging populations.

  15. Adolescent depression: meeting therapeutic challenges through an integrated narrative approach.

    Science.gov (United States)

    Bennett, Lorna Ruth

    2012-11-01

    The adolescent period is a time of transition and change often associated with losses and adjustment issues at the family, school, and individual levels. When this normal developmental transition is interrupted and compounded by depressive illness, treatment needs and nursing therapeutic challenges can be daunting. This clinically based article explores the clinical process and progress in work with a 14-year-old adolescent boy who was diagnosed with a major depressive episode. Core clinical features, distinguishing characteristics of depression in youth, as well as specific therapeutic issues and challenges are discussed. The value of an integrated clinical approach with special emphasis on narrative methods both for achievement of clinical goals and for establishing a therapeutic alliance is highlighted. The study used published literature and the author's professional and clinical experiences. Nursing therapeutics with adolescents experiencing depression must embrace a holistic integrated approach to adolescent recovery with an emphasis on what works with each unique clinical situation. Special attention to the nurse-adolescent therapeutic alliance not only facilitates achievement of therapeutic goals related to the depressive illness, but in addition, supports the shaping of a new self-narrative, wholeness, and healthy adolescent development and well-being. © 2012 Wiley Periodicals, Inc.

  16. New therapeutic approaches in psychiatry: contribution of neuroscience

    OpenAIRE

    Moulier, Virginie

    2016-01-01

    No abstract available.(Published: 17 March 2016)This paper is part of the Special Issue: New therapeutic neuroscience-based approaches in psychiatry. More papers from this issue can be found at www.socioaffectiveneuroscipsychol.netCitation: Socioaffective Neuroscience & Psychology 2016, 6: 31403 - http://dx.doi.org/10.3402/snp.v6.31403

  17. Current Therapeutic Approach to Hypertrophic Scar/span>s

    Science.gov (United States)

    Mokos, Zrinka Bukvić; Jović, Anamaria; Grgurević, Lovorka; Dumić-Čule, Ivo; Kostović, Krešimir; Čeović, Romana; Marinović, Branka

    2017-01-01

    Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scar/span>s (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome. PMID:28676850

  18. 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.

  19. 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...

  20. [The basic concept of therapeutic approaches for DMD].

    Science.gov (United States)

    Amthor, H

    2015-12-01

    Duchenne muscular dystrophy (DMD) is the most frequent hereditary neuromuscular disorder in childhood. Over the past 30 years, increasingly better standards of care have considerably improved the quality of life as well as the life expectancy of DMD patients. Despite such progress in disease management, DMD remains a devastating disorder with continuous decline of motor and cardiac function. Until recently, corticosteroids were the only treatment available to slow down, however modestly, disease progression. Importantly, novel innovative therapeutic approaches are currently being developed. This review discusses the rational and underlying molecular mechanism of these novel strategies as well as the progress made by recent clinical trials. Importantly, these new therapeutic advances bear the potential to profoundly modify the disease course of DMD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    Boisset, Sandrine; Caspar, Yvan; Sutera, Vivien; Maurin, Max

    2014-01-01

    Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline), and the aminoglycosides (streptomycin and gentamicin). 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. These new strategies have been evaluated in vitro, in axenic media and cell culture systems and/or in animal models. 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 was 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

  2. 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.

  3. Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap.

    Science.gov (United States)

    Lau, Edmund M T; Roche, Nicole A; Reddel, Helen K

    2017-05-01

    Patients with features of both asthma and chronic obstructive pulmonary disease (COPD) ('asthma-COPD overlap') experience greater symptom burden and higher risk of adverse health outcomes than those with asthma or COPD alone. However, virtually no pharmacotherapy studies have been performed in this overlap population, leading to confusion amongst clinicians regarding therapeutic approaches. Areas covered: A pragmatic approach is suggested to identify patients with typical asthma, typical COPD, and those with overlap features. Interim clinical guidance on the treatment of asthma-COPD overlap is provided, acknowledging that these recommendations are based on expert opinion given the paucity of available evidence. Expert commentary: There is an urgent need for new studies in patients with asthma-COPD overlap to evaluate the efficacy and safety of existing pharmacotherapeutic options. Multiple underlying mechanisms are likely to contribute to the development of asthma-COPD overlap and a greater understanding of these mechanisms may allow a personalised approach to therapy in the future.

  4. [Residual limb and phantom pain : Causes and therapeutic approaches].

    Science.gov (United States)

    Dwornik, G; Weiß, T; Hofmann, G O; Brückner, L

    2015-06-01

    Residual limb pain and phantom pain are severe complications following an amputation. Various reasons are responsible for these complaints. It must be distinguished between amputation stump pain, phantom sensations and phantom pain. In this paper we describe the most common reasons for stump pain and propose some non-operative therapeutic approaches. Furthermore path physiology and phantom pain therapy will be discussed. The recommendations offered in this paper are based on practical experience over three decades in a specialized out-patient department for patients with amputation injuries.

  5. [Therapeutic approaches for the treatment of facial aging].

    Science.gov (United States)

    Gauglitz, G G; Podda, M

    2015-10-01

    Over the last few decades, a magnitude of novel therapeutic approaches to battle the signs of facial aging have become available in esthetic dermatology. Comprehensive research in this area has significantly improved our understanding of the anatomy and physiology of facial aging. In order to successfully address age-related alterations in the human face, today's anti-aging treatment frequently necessitates multifaceted options. Alongside botulinum toxin and fillers, a plethora of different modalities are currently available to complete our esthetic portfolio, which are discussed in this review.

  6. Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

    Science.gov (United States)

    Farmer, Kevin L.; Li, Chengyuan

    2012-01-01

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that is associated with axonal atrophy, demyelination, blunted regenerative potential, and loss of peripheral nerve fibers. The development and progression of DPN is due in large part to hyperglycemia but is also affected by insulin deficiency and dyslipidemia. Although numerous biochemical mechanisms contribute to DPN, increased oxidative/nitrosative stress and mitochondrial dysfunction seem intimately associated with nerve dysfunction and diminished regenerative capacity. Despite advances in understanding the etiology of DPN, few approved therapies exist for the pharmacological management of painful or insensate DPN. Therefore, identifying novel therapeutic strategies remains paramount. Because DPN does not develop with either temporal or biochemical uniformity, its therapeutic management may benefit from a multifaceted approach that inhibits pathogenic mechanisms, manages inflammation, and increases cytoprotective responses. Finally, exercise has long been recognized as a part of the therapeutic management of diabetes, and exercise can delay and/or prevent the development of painful DPN. This review presents an overview of existing therapies that target both causal and symptomatic features of DPN and discusses the role of up-regulating cytoprotective pathways via modulating molecular chaperones. Overall, it may be unrealistic to expect that a single pharmacologic entity will suffice to ameliorate the multiple symptoms of human DPN. Thus, combinatorial therapies that target causal mechanisms and enhance endogenous reparative capacity may enhance nerve function and improve regeneration in DPN if they converge to decrease oxidative stress, improve mitochondrial bioenergetics, and increase response to trophic factors. PMID:22885705

  7. An Update on the Therapeutic Approach to Vernal Keratoconjunctivitis.

    Science.gov (United States)

    Esposito, Susanna; Fior, Giulia; Mori, Alessandro; Osnaghi, Silvia; Ghiglioni, Daniele

    2016-10-01

    Vernal keratoconjunctivitis (VKC) is an inflammatory disease of the ocular surface. It commonly occurs in the first decade of life, has a wide geographical distribution, and usually occurs in warm, dry areas. The pathogenesis of VKC seems to have an immune, nervous, and endocrine basis. The most common eye symptoms are itching, discharge, tearing, eye irritation, redness of the eyes, and photophobia. Although VKC generally has a good prognosis, the lack of clarity regarding the origin of the disease makes treatment a challenge for pediatricians and ophthalmologists. The purpose of this review is to discuss the pathogenesis, clinical features, and diagnostic criteria in VKC, with a focus on its therapeutic management. The selection of a therapeutic scheme from the many available options is based on clinical features and the personal preferences of both physicians and patients. Due to the lack of uniform grading of disease severity, there is no worldwide consensus on first-line and second-line therapeutic approaches. The choice of treatment for long-term moderate to severe VKC includes topical cyclosporine or tacrolimus. Further data are needed to define the minimal effective concentration and the safety of these drugs in eye drops and to clarify the diagnosis of VKC in patients who require these drugs. Finally, while promising newly discovered drugs are expected to enter into clinical practice, further studies on their efficacy and safety are required.

  8. Circular permutation prediction reveals a viable backbone disconnection for split proteins: an approach in identifying a new functional split intein.

    Directory of Open Access Journals (Sweden)

    Yun-Tzai Lee

    Full Text Available Split-protein systems have emerged as a powerful tool for detecting biomolecular interactions and reporting biological reactions. However, reliable methods for identifying viable split sites are still unavailable. In this study, we demonstrated the feasibility that valid circular permutation (CP sites in proteins have the potential to act as split sites and that CP prediction can be used to search for internal permissive sites for creating new split proteins. Using a protein ligase, intein, as a model, CP predictor facilitated the creation of circular permutants in which backbone opening imposes the least detrimental effects on intein folding. We screened a series of predicted intein CPs and identified stable and native-fold CPs. When the valid CP sites were introduced as split sites, there was a reduction in folding enthalpy caused by the new backbone opening; however, the coincident loss in entropy was sufficient to be compensated, yielding a favorable free energy for self-association. Since split intein is exploited in protein semi-synthesis, we tested the related protein trans-splicing (PTS activities of the corresponding split inteins. Notably, a novel functional split intein composed of the N-terminal 36 residues combined with the remaining C-terminal fragment was identified. Its PTS activity was shown to be better than current reported two-piece intein with a short N-terminal segment. Thus, the incorporation of in silico CP prediction facilitated the design of split intein as well as circular permutants.

  9. 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...

  10. Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses.

    Science.gov (United States)

    Kohan, R; Cismondi, I A; Oller-Ramirez, A M; Guelbert, N; Anzolini, Tapia V; Alonso, G; Mole, S E; de Kremer, Dodelson R; de Halac, Noher I

    2011-06-01

    The Neuronal Ceroid Lipofuscinoses (NCLs) are lysosomal storage diseases (LSDs) affecting the central nervous system (CNS), with generally recessive inheritance. They are characterized by pathological lipofuscin-like material accumulating in cells. The clinical phenotypes at all onset ages show progressive loss of vision, decreasing cognitive and motor skills, epileptic seizures and premature death, with dementia without visual loss prominent in the rarer adult forms. Eight causal genes, CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8, CLN8, with more than 265 mutations and 38 polymorphisms (http://www.ucl.ac.uk/ncl) have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study. Some therapeutic strategies applied to other LSDs with significant systemic involvement would not be effective in NCLs due to the necessity of passing the blood brain barrier to prevent the neurodegeneration, repair or restore the CNS functionality. There are therapies for the NCLs currently at preclinical stages and under phase 1 trials to establish safety in affected children. These approaches involve enzyme replacement, gene therapy, neural stem cell replacement, immune therapy and other pharmacological approaches. In the next decade, progress in the understanding of the natural history and the biochemical and molecular cascade of events relevant to the pathogenesis of these diseases in humans and animal models will be required to achieve significant therapeutic advances.

  11. 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.

  12. 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

  13. Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair

    Science.gov (United States)

    Knott, Eric P.; Assi, Mazen; Rao, Sudheendra N. R.; Ghosh, Mousumi; Pearse, Damien D.

    2017-01-01

    A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies. The only known negative regulators of cyclic nucleotides are a family of enzymes called phosphodiesterases (PDEs) that hydrolyze cyclic nucleotides into adenosine monophosphate (AMP) or guanylate monophosphate (GMP). Herein, we discuss the structure and physiological function as well as the roles PDEs play in pathological processes of the diseased or injured CNS. Further we review the approaches that have been employed therapeutically in experimental paradigms to block PDE expression or activity and in turn elevate cyclic nucleotide levels to mediate neuroprotection or neurorepair as well as discuss both the translational pathway and current limitations in moving new PDE-targeted therapies to the clinic. PMID:28338622

  14. [Nanotechnology offers a promising therapeutic approach for hypertension treatment].

    Science.gov (United States)

    Martín Giménez, V M; Kassuha, D; Manucha, W

    Hypertension is a medical condition considered one of the most important public health problems in developed countries, affecting around one billion people. Therefore, the study of its mechanisms, development and treatment is a priority. Of particular interest are the multiple contributing factors, and efforts by experts to fully understand it are also important. However, studies are currently insufficient and consequently, attention is focused on the exploration of new therapeutic approaches. This raises a growing interest in nanotechnology given the ability of certain structures to mimic the behavior of extracellular matrices. This opens a promising field in the treatment of diseases such as hypertension, where it stands to tissue engineering and its potential applications incorporating concepts such as controlled release drug, reduced side effects and receptor activation locally. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Engineering therapeutic proteins for cell entry: the natural approach.

    Science.gov (United States)

    Guillard, Sandrine; Minter, Ralph R; Jackson, Ronald H

    2015-03-01

    Owing to the challenges of cell entry, protein-based therapies have so far been restricted to extracellular targets, whereas intracellular targets have been almost exclusively addressed by small molecules. The specificity and potency of proteins would enable them to be effective intracellular drugs, provided that the proteins are delivered efficiently to appropriate intracellular compartments within specific cell types. By mimicking the natural mechanisms of toxins and other natural proteins, new intracellular delivery systems are being developed, the first of which are showing clinical efficacy. This review highlights a range of ingenious approaches designed to adapt natural entry mechanisms to facilitate delivery of proteins and open up a range of validated intracellular targets to modulation by potent and specific therapeutic drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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.

  17. 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.

  18. Non-genetic therapeutic approaches to Canavan disease.

    Science.gov (United States)

    Roscoe, Rebecca B; Elliott, Christina; Zarros, Apostolos; Baillie, George S

    2016-07-15

    Canavan disease (CD) is a rare leukodystrophy characterized by diffuse spongiform white matter degeneration, dysmyelination and intramyelinic oedema with consequent impairment of psychomotor development and early death. The molecular cause of CD has been identified as being mutations of the gene encoding the enzyme aspartoacylase (ASPA) leading to its functional deficiency. The physiological role of ASPA is to hydrolyse N-acetyl-l-aspartic acid (NAA), producing l-aspartic acid and acetate; as a result, its deficiency leads to abnormally high central nervous system NAA levels. The aim of this article is to review what is currently known regarding the aetiopathogenesis and treatment of CD, with emphasis on the non-genetic therapeutic strategies, both at an experimental and a clinical level, by highlighting: (a) major related hypotheses, (b) the results of the available experimental simulatory approaches, as well as (c) the relevance of the so far examined markers of CD neuropathology. The potential and the limitations of the current non-genetic neuroprotective approaches to the treatment of CD are particularly discussed in the current article, in a context that could be used to direct future experimental and (eventually) clinical work in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Therapeutic approaches for portal biliopathy: A systematic review.

    Science.gov (United States)

    Franceschet, Irene; Zanetto, Alberto; Ferrarese, Alberto; Burra, Patrizia; Senzolo, Marco

    2016-12-07

    Portal biliopathy (PB) is defined as the presence of biliary abnormalities in patients with non-cirrhotic/non-neoplastic extrahepatic portal vein obstruction (EHPVO) and portal cavernoma (PC). The pathogenesis of PB is due to ab extrinseco compression of bile ducts by PC and/or to ischemic damage secondary to an altered biliary vascularization in EHPVO and PC. Although asymptomatic biliary abnormalities can be frequently seen by magnetic resonance cholangiopancreatography in patients with PC (77%-100%), only a part of these (5%-38%) are symptomatic. Clinical presentation includes jaundice, cholangitis, cholecystitis, abdominal pain, and cholelithiasis. In this subset of patients is required a specific treatment. Different therapeutic approaches aimed to diminish portal hypertension and treat biliary strictures are available. In order to decompress PC, surgical porto-systemic shunt or transjugular intrahepatic porto-systemic shunt can be performed, and treatment on the biliary stenosis includes endoscopic (Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy, balloon dilation, stone extraction, stent placement) and surgical (bilioenteric anastomosis, cholecystectomy) approaches. Definitive treatment of PB often requires multiple and combined interventions both on vascular and biliary system. Liver transplantation can be considered in patients with secondary biliary cirrhosis, recurrent cholangitis or unsuccessful control of portal hypertension.

  20. Freezing Nitrogen Ethanol Composite May be a Viable Approach for Cryotherapy of Human Giant Cell Tumor of Bone.

    Science.gov (United States)

    Wu, Po-Kuei; Chen, Cheng-Fong; Wang, Jir-You; Chen, Paul Chih-Hsueh; Chang, Ming-Chau; Hung, Shih-Chieh; Chen, Wei-Ming

    2017-06-01

    complications were evaluated at a minimum of 19 months followup (mean, 24 months; range, 19-30 months). Freshly prepared freezing nitrogen ethanol composite froze to -136° C and achieved -122° C isotherm across a piece of 10 ± 0.50-mm-thick bone with a freezing rate of -34° C per minute, a temperature expected to meet clinical tumor-killing requirements. Human GCT tissues revealed histologic changes including shrinkage in morphologic features of multinucleated giant cells in the liquid nitrogen (202 ± 45 μm; p = 0.006) and freezing nitrogen ethanol composite groups (169 ± 27.4 μm; p freezing nitrogen ethanol composite-treated samples. Numbers of blood vessels and human origin tumor cells also were decreased by freezing nitrogen ethanol composite and liquid nitrogen treatment in the GCT-grafted chicken chorioallantoic membrane model. Seven patients with GCT treated by curettage and adjuvant cryotherapy by use of freezing nitrogen ethanol composite preparation had no intra- or postoperative complications related to the freezing, and no recurrences during the study surveillance period. These preliminary in vitro and clinical findings suggest that freezing nitrogen ethanol composite may be an effective cryogen showing ex vivo and in vivo tumor cryoablation comparable to liquid nitrogen. The semisolid phase and proper thermal conduction might avoid some of the disadvantages of liquid nitrogen in cryotherapy, but a larger clinical study is needed to confirm these findings. Level IV, therapeutic study.

  1. Therapeutic approach to bronchiolitis: why pediatricians continue to overprescribe drugs?

    Directory of Open Access Journals (Sweden)

    de Seta Federica

    2010-10-01

    Full Text Available Abstract Background Bronchiolitis guidelines suggest that neither bronchodilators nor corticosteroids, antiviral and antibacterial agents should be routinely used. Although recommendations, many clinicians persistently prescribe drugs for bronchiolitis. Aim of the study To unravel main reasons of pediatricians in prescribing drugs to infants with bronchiolitis, and to possibly correlate therapeutic choices to the severity of clinical presentation. Also possible influence of socially deprived condition on therapeutic choices is analyzed. Methods Patients admitted to Pediatric Division of 2 main Hospitals of Naples because of bronchiolitis in winter season 2008-2009 were prospectively analyzed. An RDAI (Respiratory Distress Assessment Instrument score was assessed at different times from admission. Enrolment criteria were: age 1-12 months; 1st lower respiratory infection with cough and rhinitis with/without fever, wheezing, crackles, tachypnea, use of accessory muscles, and/or nasal flaring, low oxygen saturation, cyanosis. Social deprivation status was assessed by evaluating school graduation level of the origin area of the patients. A specific questionnaire was submitted to clinicians to unravel reasons of their therapeutic behavior. Results Eighty-four children were enrolled in the study. Mean age was 3.5 months. Forty-four per cent of patients presented with increased respiratory rate, 70.2% with chest retractions, and 7.1% with low SaO2. Mean starting RDAI score was 8. Lung consolidation was found in 3.5% on chest roentgenogram. Data analysis also unraveled that 64.2% matched clinical admission criteria. Social deprivation status analysis revealed that 72.6% of patients were from areas "at social risk". Evaluation of length of stay vs. social deprivation status evidenced no difference between "at social risk" and "not at social risk" patients. Following therapeutic interventions were prescribed: nasal suction (64.2%, oxygen administration (7

  2. Mutual coupling of hydrologic and hydrodynamic models - a viable approach for improved large-scale inundation estimates?

    Science.gov (United States)

    Hoch, Jannis; Winsemius, Hessel; van Beek, Ludovicus; Haag, Arjen; Bierkens, Marc

    2016-04-01

    Due to their increasing occurrence rate and associated economic costs, fluvial floods are large-scale and cross-border phenomena that need to be well understood. Sound information about temporal and spatial variations of flood hazard is essential for adequate flood risk management and climate change adaption measures. While progress has been made in assessments of flood hazard and risk on the global scale, studies to date have made compromises between spatial resolution on the one hand and local detail that influences their temporal characteristics (rate of rise, duration) on the other. Moreover, global models cannot realistically model flood wave propagation due to a lack of detail in channel and floodplain geometry, and the representation of hydrologic processes influencing the surface water balance such as open water evaporation from inundated water and re-infiltration of water in river banks. To overcome these restrictions and to obtain a better understanding of flood propagation including its spatio-temporal variations at the large scale, yet at a sufficiently high resolution, the present study aims to develop a large-scale modeling tool by coupling the global hydrologic model PCR-GLOBWB and the recently developed hydrodynamic model DELFT3D-FM. The first computes surface water volumes which are routed by the latter, solving the full Saint-Venant equations. With DELFT3D FM being capable of representing the model domain as a flexible mesh, model accuracy is only improved at relevant locations (river and adjacent floodplain) and the computation time is not unnecessarily increased. This efficiency is very advantageous for large-scale modelling approaches. The model domain is thereby schematized by 2D floodplains, being derived from global data sets (HydroSHEDS and G3WBM, respectively). Since a previous study with 1way-coupling showed good model performance (J.M. Hoch et al., in prep.), this approach was extended to 2way-coupling to fully represent evaporation

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-09-01

    Full Text Available 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.

  5. Endoscopic Therapeutic Approach for Dysplasia in Inflammatory Bowel Disease.

    Science.gov (United States)

    Hong, Sung Noh

    2017-09-01

    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.

  6. 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

  7. Halitosis: a review of associated factors and therapeutic approach

    Directory of Open Access Journals (Sweden)

    José Roberto Cortelli

    2008-08-01

    Full Text Available Halitosis or bad breath is an oral health condition characterized by unpleasant odors emanating consistently from the oral cavity. The origin of halitosis may be related both to systemic and oral conditions, but a large percentage of cases, about 85%, are generally related to an oral cause. Causes include certain foods, poor oral health care, improper cleaning of dentures, dry mouth, tobacco products and medical conditions. Oral causes are related to deep carious lesions, periodontal disease, oral infections, peri-implant disease, pericoronitis, mucosal ulcerations, impacted food or debris and, mainly, tongue coating. Thus, the aim of the present review was to describe the etiological factors, prevalence data and the therapeutic mechanical and chemical approaches related to halitosis. In general, halitosis most often results from the microbial degradation of oral organic substrates including volatile sulfur compounds (VSC. So far, there are few studies evaluating the prevalence of oral malodor in the world population. These studies reported rates ranging from 22% to more than 50%. The mechanical and chemical treatment of halitosis has been addressed by several studies in the past four decades. Many authors agree that the solution of halitosis problems must include the reduction of the intraoral bacterial load and/or the conversion of VSC to nonvolatile substrates. This could be achieved by therapy procedures that reduce the amount of microorganisms and substrates, especially on the tongue.

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

    Science.gov (United States)

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

    2016-09-13

    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.

  9. [Therapeutic approaches for obesity and comorbidities in young immigrants].

    Science.gov (United States)

    Wiegand, S; Babitsch, B

    2013-04-01

    The prevalence of overweight and obesity is higher in children and adolescents with a migrational background. However, if the country of origin is taken into account, the picture of these differences becomes more complex and more heterogeneous. Predictors for obesity and the ethnic differences are manifold and can be roughly differentiated into cultural, social and individual causes as well as into causes related to the process of acculturation. There are special problems in the long-term health care of obese adolescents with a migrational background. The most important are (1) treatment delay, (2) different concepts of a healthy (problematic) body weight, (3) barriers in diagnostics and treatment of rare secondary disorders and (4) puberty-related changes in lifestyle (increased media use, decreased physical activity and unfavourable daily routines). Therapeutic approaches are only sustainable and effective when the underlying concepts are multiprofessional and multimodal, and are embedded into the family and cultural contexts. Adolescents with a migrational background need culture-adapted nutrition, exercise and media consumption counselling. Such offers have to be (further) developed in accordance with family background, with youth culture and adolescent stage of development.

  10. Resurfacing total hip replacement--a therapeutical approach in postmenopausal women with osteoporosis and hip arthrosis

    National Research Council Canada - National Science Library

    Popescu, D; Ene, R; Cirstoiu, C

    2011-01-01

    Patients with incipient hip arthrosis may benefit from a relatively new therapeutical approach using resurfacing total hip replacement, but in those with associated osteoporosis, this type of surgical...

  11. Inflammatory Bowel Disease: Pathophysiology and Current Therapeutic Approaches.

    Science.gov (United States)

    Abraham, Bincy P; Ahmed, Tasneem; Ali, Tauseef

    2017-01-01

    Inflammatory bowel diseases, most commonly categorized as Crohn's disease and ulcerative colitis, are immune mediated chronic inflammatory disorders of the gastrointestinal tract. The etiopathogenesis is multifactorial with different environmental, genetic, immune mediated, and gut microbial factors playing important role. The current goals of therapy are to improve clinical symptoms, control inflammation, prevent complications, and improve quality of life. Different therapeutic agents, with their indications, mechanisms of action, and side effects are discussed in this chapter. Anti-integrin therapy, a newer therapeutic class, with its potential beneficial role in both Crohn's disease and ulcerative colitis is also mentioned. In the end, therapeutic algorithms for both diseases are reviewed.

  12. 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

  13. [Current diagnostic and therapeutic approaches in liver injuries].

    Science.gov (United States)

    Vyhnánek, F; Denemark, L; Duchác, V

    2003-01-01

    The recent improvements in hospital care system (centralized specialized care) and the use of new imaging methods and modern technologies in surgical treatment have greatly enhanced successful outcomes of therapy in liver injury. The aim of the study was to evaluate the contribution of procedures included in the diagnostic-therapeutic algorithms to the treatment of blunt injury to the liver in our patient population. Our group consisted of 43 patients with blunt injury to the liver who were treated at the Emergency Department between 1998 and 2002. In 28 patients, blunt injury was part of polytrauma, in 7 patients it was associated with thoraco-abdominal injury and, in 8 patients, it was the only trauma sustained. The diagnosis and therapy were based on the algorithm currently used for treating liver injury at the Emergency Department. In addition to clinical examination and assessment of the actual status of hemodynamics, spinal computed tomography was carried out to establish the therapeutic procedure. Fourteen patients were treated conservatively according to the criteria of a non-surgical approach and 29 patients underwent urgent surgery. Indications for revision surgery included, apart from signs of ongoing abdominal bleeding related to liver injury, combined spleen and kidney trauma. All patients with thoraco-abdominal involvement had laparotomy; in addition, four underwent thoracotomy including repair of the lacerated lung by suturing and three patients required suturing of a rupture of the right part of the diaphragm. In the patients treated conservatively, 10 showed spontaneous regression of parenchymal hematomas and four had to be treated by suction drainage. Out of 29 patients operated on, five died with signs of an irreversible hemorrhagic shock from multiple trauma and one died of multiple organ failure. The principal criterion determining therapy in blunt liver injury is the patient's hemodynamic status; laparotomy is mandatory in intra

  14. Quality of life, coping strategies and support needs of women seeking Traditional Chinese Medicine for infertility and viable pregnancy in Australia: a mixed methods approach.

    Science.gov (United States)

    Ried, Karin; Alfred, Ann

    2013-04-09

    Infertility affects about 15% of couples in Western-societies with most progressing to fertility clinics for treatment. Despite being common, infertility is often experienced as a lonely road for affected couples. In this paper we expand on our previously published findings of women's experiences with infertility or difficulty of viable pregnancy who had sought Traditional Chinese Medicine (TCM) therapy in Australia, and focus on women's quality of life, coping strategies, and support needs. We applied mixed methods using the Tuebingen Quality of Life and the COPE questionnaires and in-depth interviews with 25 women with primary or secondary infertility, recurrent miscarriages or unexplained stillbirth, and who had consulted a TCM practitioner. We used a thematic approach to analyse the interviews, and descriptive statistics to evaluate questionnaire responses. Women reported through both questionnaires and interviews compromised quality of life due to the high level of distress, guilt, grief, and frustration caused by infertility. However, our women represented a highly motivated sample, actively seeking alternative support. While the TCM approach to infertility management increased women's sense of personal agency and control through education and continuity of care, the need for greater understanding and support on a societal level remains. In infertility, ongoing emotional and instrumental support is pivotal to the wellbeing and quality of life of the affected. Traditional Chinese Medicine addresses some support needs in infertility not routinely available in the Western model of care. More peer-led and professional-led support groups are greatly needed for women experiencing infertility to help break isolation and raise awareness of integrative approaches to fertility management.

  15. Recent novel tumor gatekeepers and potential therapeutic approaches

    African Journals Online (AJOL)

    cancer stem cells in prostate tumors. These outcomes suggest that CD54 can be used as a prostate cancer stem cell marker and will provide a novel potential therapeutic target through. CD54-Notch1 signaling in prostate cancer [12]. Lung cancer is a most common cancer and leading cause of deaths worldwide. Targeted.

  16. Experimental Approaches Toward Histone Acetyltransferase Inhibitors as Therapeutics

    NARCIS (Netherlands)

    Dekker, Frank; Tollefsbol, Trygve

    2016-01-01

    This chapter comprises the most recent developments with respect to the role of human histone acetyltransferases (HATs) in diseases and the potential therapeutic applications of HAT inhibitors. HATs form a diverse group of mainly nuclear enzymes that play an important role in the acetylation of

  17. Today prospects for tissue engineering therapeutic approach in dentistry.

    Science.gov (United States)

    Bossù, Maurizio; Pacifici, Andrea; Carbone, Daniele; Tenore, Gianluca; Ierardo, Gaetano; Pacifici, Luciano; Polimeni, Antonella

    2014-01-01

    In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have recently been isolated and characterized from tooth-related tissues and they might represent, in the near future, a new gold standard in the regeneration of all oral tissues. The aim of our review is to provide an overview on the topic reporting the current knowledge for each class of dental stem cells and to identify their potential clinical applications as therapeutic tool in various branches of dentistry.

  18. Today Prospects for Tissue Engineering Therapeutic Approach in Dentistry

    Directory of Open Access Journals (Sweden)

    Maurizio Bossù

    2014-01-01

    Full Text Available In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have recently been isolated and characterized from tooth-related tissues and they might represent, in the near future, a new gold standard in the regeneration of all oral tissues. The aim of our review is to provide an overview on the topic reporting the current knowledge for each class of dental stem cells and to identify their potential clinical applications as therapeutic tool in various branches of dentistry.

  19. Today Prospects for Tissue Engineering Therapeutic Approach in Dentistry

    OpenAIRE

    Maurizio Bossù; Andrea Pacifici; Daniele Carbone; Gianluca Tenore; Gaetano Ierardo; Luciano Pacifici; Antonella Polimeni

    2014-01-01

    In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have r...

  20. 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.

  1. Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Dimitroulis, Ioannis A

    2014-09-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with no clear etiology and few therapeutic options. Growth factors that act as mediators in the development of this disease might be important therapeutic targets. Nintedanib is a triple-tyrosine kinase inhibitor and a potent antagonist of growth factors such as platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor, and it is currently evaluated in clinical trials as a potential IPF therapy. Treatment with nintedanib may slow decline in lung function, decrease the frequency of exacerbations, and improve quality of life in subjects with IPF. This observation, together with extensive safety and pharmacokinetic data from studies of nintedanib in malignancy, led the way for the clinical development of this drug in IPF. Observations from clinical trials, together with the preclinical data, suggest that nintedanib may become an important therapeutic option for individuals with IPF. High-dose nintedanib improved the quality of life, slowed the progression of lung fibrosis and the decline of lung function, and reduced the rate of exacerbations in individuals with mild and moderate IPF. This is a short review based on the available data (September 2013) on nintedanib. Copyright © 2014 by Daedalus Enterprises.

  2. Managing Viable Knowledge

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.; Vriens, D.J.

    2002-01-01

    In this paper, Beer's Viable System Model (VSM) is applied to knowledge management. Based on the VSM, domains of knowledge are identified that an organization should possess to maintain its viability. The logic of the VSM is also used to support the diagnosis, design and implementation of the

  3. Virus-induced Systemic Vasculitides: New Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Loïc Guillevin

    2004-01-01

    Full Text Available The best therapeutic strategy in virus-induced vasculitides should take into account the etiology of the disease and be adapted to the pathogenesis. The combination of antiviral treatments and plasma exchanges has been proven effective in polyarteritis nodosa (PAN. In human immunodeficiency virus (HIV-related vasculitis this strategy is also effective and does not jeopardize, like cytotoxic agents, the outcome of AIDS. In vasculitis related to HCV-associated cryoglobulinemia, plasma exchanges improve the outcome but the poor effectiveness of antiviral drugs is not able to favor, usually, a definite recovery of the patients and relapses are frequent.

  4. Reconstructing the pyramid as a therapeutic approach to rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    G. Ferraccioli

    2011-09-01

    Full Text Available Several recent clinical studies have clearly established that rheumatoid arthritis (RA is a disease identifiable since its early phases, a disease that can be adequately and efficaciously treated provided the therapeutic program can be started early on. To reach the aim of controlling effectively the disease and of leading the patients to live a normal life, several points must be fulfilled. The first is an early diagnosis obtained through a careful clinical examination along with an appropriate laboratory immunological work-up, followed by an adequate monotherapy within the first 4 months from symptoms onset. The second is the therapeutic re-assessment that needs to be done every three months, to start a possible combination therapy (COMBO, in order to rescue monotherapy failures. The third is the initiation of biological response modifiers (BRMs within 6 months from monotherapy onset, within 3 months from COMBO in the most resistant cases. Having at hand several molecules with BRMs characteristics, we believe that the future appears much more favourable in most cases even in those with the severe disease.

  5. Therapeutic approaches for ophthalmic problems in juvenile rheumatoid arthritis.

    Science.gov (United States)

    O'Brien, J M; Albert, D M

    1989-08-01

    Juvenile rheumatoid arthritis is a disease of children which is chronic and painful, with the potential to produce permanent disability and blindness in a significant portion of cases. The treatment we provide these children may also disable them. Managing this disease process and caring for these patients is a challenging task in which therapeutic efficacy must be continually balanced against treatment morbidity. With respect to ocular disease, we must particularly recognize the difficulties parents have in treating a characteristically asymptomatic process with interventions that can produce unpleasant symptomatology. The importance of discussion of therapeutic decisions with parent and child cannot be overemphasized. Children with JRA should be carefully classified and those at greatest risk for development of ocular disease should receive frequent ophthalmologic screening exams. Early intervention and aggressive medical management of intraocular inflammation will minimize morbidity and permanent visual compromise. Patients should also be closely monitored for ocular side effects of therapies directed against articular disease. Procedures employed for treatment of cataract, glaucoma, corneal, and vitreal opacities must take into account the risk and complications of surgical intervention in the JRA patient prone to perioperative inflammation.

  6. Therapeutical approaches under investigation for treatment of Chagas disease.

    Science.gov (United States)

    Bahia, Maria Terezinha; Diniz, Lívia de Figueiredo; Mosqueira, Vanessa Carla Furtado

    2014-09-01

    A century after its discovery, American trypanosomiasis or Chagas disease remains a serious health problem in Latin America, where it affects around 7 - 8 million people. The prevalence of Chagas disease in the poorer parts of the world has meant that it has largely been neglected with limited progress that made in identifying new drugs for the treatment. The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available for Chagas disease with limitations that include variable efficacy, long treatment courses and toxicity. This review focuses on different therapeutic strategies that have been used for the discovery of new treatments for Chagas disease. These include combination chemotherapy, drug repositioning, re-dosing regimens for current drugs and the identification of new drugs with specified target profiles. There are currently several reasons for a more optimistic view about chemotherapy with Chagas disease. However, despite some progress being made in preclinical studies, there is yet to be an ideal drug or formulation for human treatment. One major drawback in the evaluation of potential Chagas disease therapeutics is the lack of tools available to perform the said evaluation. Indeed, there is a great need to discover a better biomarker that could determine the efficacy of potential chemotherapeutics in treated patients.

  7. Classification and therapeutic approaches in autoimmune hemolytic anemia: an update.

    Science.gov (United States)

    Michel, Marc

    2011-12-01

    Autoimmune hemolytic anemia (AIHA) is an uncommon autoantibody-mediated immune disorder that affects both children and adults. The diagnosis of AIHA relies mainly on the direct antiglobulin test, which is a highly sensitive and relatively specific test. The classification of AIHA is based on the pattern of the direct antiglobulin test and on the immunochemical properties of the autoantibody (warm or cold type), but also on the presence or absence of an underlying condition or disease (secondary vs primary AIHAs) that may have an impact on treatment and outcome. The distinction between AIHAs due to warm antibody (wAIHA) and AIHAs due to cold antibody is a crucial step of the diagnostic procedure as it influences the therapeutic strategy. Whereas corticosteroids are the cornerstone of treatment in wAIHA, they have no or little efficacy in cold AIHA. In wAIHA that is refractory or dependent to corticosteroids, splenectomy and rituximab are both good alternatives and the benefit?risk ratio of each option must be discussed on an individual basis. In chronic agglutinin disease, the most common variety of cold AIHA in adults, beyond supportive measures, rituximab given either alone or in combination with chemotherapy may be helpful. In this article, the classification of AIHA and the recent progress in therapeutics are discussed.

  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. New therapeutic approaches for the treatment of obesity.

    Science.gov (United States)

    Saltiel, Alan R

    2016-01-27

    This review discusses current and future pharmacological approaches to the treatment of obesity, with a focus on the biological control of energy balance. Copyright © 2016, American Association for the Advancement of Science.

  10. [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.

  11. Infective endocarditis: diagnostic and therapeutic approach in emergency medicine

    Directory of Open Access Journals (Sweden)

    Rita Previati

    2007-02-01

    Full Text Available The infective endocarditis is an uncommon disease in the Emergency Department. Anyway, the emergency physician may be in front of the complications of this disease. A case of a patient with fever, laboratory signs of infection and an acute heart failure is described in this article. The final diagnosis was infective endocarditis with vegetations on the aortic valve and severe valvular regurgitation. The definition of infective endocarditis according to the major and minor criteria for the diagnosis is discussed. The echocardiography is central in the diagnosis and management of patients with infective endocarditis in the emergency setting, even if the clinical suspicion is very important. The main available therapeutic options in according to the Internation Guidelines are evaluated. The possible complications are also discussed. Several clinical and echocardiographic features identify patients at high risk for a complicated course or with a need for surgery.

  12. Targeting cancer cell mitochondria as a therapeutic approach: recent updates.

    Science.gov (United States)

    Cui, Qingbin; Wen, Shijun; Huang, Peng

    2017-06-01

    Mitochondria play a key role in ATP generation, redox homeostasis and regulation of apoptosis. Due to the essential role of mitochondria in metabolism and cell survival, targeting mitochondria in cancer cells is considered as an attractive therapeutic strategy. However, metabolic flexibility in cancer cells may enable the upregulation of compensatory pathways, such as glycolysis to support cancer cell survival when mitochondrial metabolism is inhibited. Thus, compounds capable of both targeting mitochondria and inhibiting glycolysis may be particularly useful to overcome such drug-resistant mechanism. This review provides an update on recent development in the field of targeting mitochondria and novel compounds that impact mitochondria, glycolysis or both. Key challenges in this research area and potential solutions are also discussed.

  13. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Alok Kumar

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.

  14. 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. PMID:26306443

  15. [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.

  16. [Severe hyperemesis gravidarum--pathophysiologic observations and new therapeutic approach].

    Science.gov (United States)

    Glasbrenner, B; Swobodnik, W; Malfertheiner, P; Ditschuneit, H

    1991-04-01

    It is reported on a 27 year old female patient who was hospitalized twice during her first pregnancy (16th and 28th week) because of severe hyperemesis gravidarum. Severe clinical symptoms associated with severe alterations in the clinical chemistry posed a series of differential diagnoses. Several diseases as potential causes for unappeasable vomiting were taken into account. All traditional therapeutic efforts to relieve hyperemesis gravidarum including H2-blockers in high dosages were not successful. Treatment with omeprazole proved to be effective by stopping the vomiting immediately. After the delivery of a healthy child in the 37th week of pregnancy, several investigations were performed to exclude organic diseases. Etiology and symptoms of hyperemesis gravidarum are discussed with regard to the gastrointestinal tract and thyroid gland function.

  17. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Science.gov (United States)

    Kumar, Alok; Ghosh, Devlina; Singh, R. L.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients. PMID:26317018

  18. 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.

  19. Plasma Kallikrein Inhibitors in Cardiovascular Disease: An Innovative Therapeutic Approach.

    Science.gov (United States)

    Kolte, Dhaval; Shariat-Madar, Zia

    2016-01-01

    Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine protease plasma kallikrein, and circulates in plasma bound to high molecular weight kininogen. Plasma prekallikrein is activated to plasma kallikrein by activated factor XII or prolylcarboxypeptidase. Plasma kallikrein regulates the activity of multiple proteolytic cascades in the cardiovascular system such as the intrinsic pathway of coagulation, the kallikrein-kinin system, the fibrinolytic system, the renin-angiotensin system, and the complement pathways. As such, plasma kallikrein plays a central role in the pathogenesis of thrombosis, inflammation, and blood pressure regulation. Under physiological conditions, plasma kallikrein serves as a cardioprotective enzyme. However, its increased plasma concentration or hyperactivity perpetuates cardiovascular disease (CVD). In this article, we review the biochemistry and cell biology of plasma kallikrein and summarize data from preclinical and clinical studies that have established important functions of this serine protease in CVD states. Finally, we propose plasma kallikrein inhibitors as a novel class of drugs with potential therapeutic applications in the treatment of CVDs.

  20. Impact of epigenetic mechanisms on therapeutic approaches of hemoglobinopathies.

    Science.gov (United States)

    Costa, Dario; Capuano, Maria; Sommese, Linda; Napoli, Claudio

    2015-08-01

    Hemoglobinopathies are inherited disorders characterized by anomalies of structure, function or production of globin chains. From conception to adulthood, the different expressions over time of the various globin chains depend on the activation/deactivation of different globin genes through methylation and chromatin remodeling processes. The most significant clinical disorders are β-thalassemia and sickle cell disease. The clinical management of these disorders engages regular blood transfusions. Another therapy is represented by allogeneic hematopoietic cells transplantation. There are several studies based on the innovative therapeutic strategies that involve some epigenetic mechanisms focused on the reactivation of γ-globin gene expression. The induction of fetal hemoglobin expression in adulthood is an effective therapy for these disorders. Particularly interesting are the recent data on miRNAs showing the interaction of these molecules with different transcription factors such as MYB, KLF, BCL11A and SOX6. The aim of this review was to report an update on the dynamic epigenetic modifications as targets for therapy in hemoglobinopathies. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Injuries caused by arthropods: diagnostic and therapeutic approach in ER

    Directory of Open Access Journals (Sweden)

    Dutto Moreno

    2009-04-01

    Full Text Available Injuries caused by arthropods, primarily insects and arachnids, represent a significant source of lesions and allergies even in Italy, a country that has a negligible number of species with important toxicological characteristics from an emergency medicine point of view; unlike areas such as the Americas or Africa (including northern Africa where highly toxic autochthonous species are present, whose bite or sting can be life-threatening. Medical consultation both in hospital Emergency Rooms and general practitioners’ surgeries is markedly seasonal, occurring mainly in the spring and summer (April – September, consistent with arthropod activity. At the current time, in Italy, urgent acute arthropod-related injuries are rare and usually involve type I hypersensitivity, and in most cases they are localised lesions that cause discomfort. The aim of the article is to briefly summarise the species of insects and arachnids that are most frequently cause for medical consultation in Italy and to provide assistance in the diagnostic and therapeutic plan, focusing in particular on the importance of health education that in many acute arthropod-derived cases can play an important part in preventing reoccurrence.

  2. Behavioural variant frontotemporal dementia: clinical and therapeutic approaches.

    Science.gov (United States)

    Fernández-Matarrubia, M; Matías-Guiu, J A; Moreno-Ramos, T; Matías-Guiu, J

    2014-10-01

    Behavioural variant frontotemporal dementia (bvFTD) is the most frequent presentation in the clinical spectrum of frontotemporal dementia (FTD) and it is characterised by progressive changes in personality and conduct. Major breakthroughs in molecular biology and genetics made during the last two decades have lent us a better understanding of this syndrome, which may be the first manifestation in many different neurodegenerative diseases. We reviewed the main epidemiological, clinical, diagnostic and therapeutic aspects of bvFTD. Most cases manifest sporadically and the average age of onset is 58 years. Current criteria for bvFTD propose three levels of diagnostic certainty: possible, probable, and definite. Clinical diagnosis is based on a detailed medical history provided by family members and caregivers, in conjunction with neuropsychological testing. Treatments which have been used in bvFDT to date are all symptomatic and their effectiveness is debatable. New drugs designed for specific molecular targets that are implicated in frontotemporal lobar degeneration are being developed. BvFDT is a frequent cause of dementia. It is a non-specific syndrome associated with heterogeneous histopathological and biomolecular findings. The definition of clinical subtypes complemented by biomarker identification may help predict the underlying pathology. This knowledge, along with the development of drugs designed for molecular targets, will offer new treatment possibilities. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  3. Treatment of polyarteritis nodosa with tocilizumab: a new therapeutic approach?

    Science.gov (United States)

    Saunier, Aurélie; Issa, Nahéma; Vandenhende, Marie-Anne; Morlat, Philippe; Doutre, Marie-Sylvie; Bonnet, Fabrice

    2017-01-01

    We describe the effect of interleukin 6 (IL-6) blockade using tocilizumab (TCZ) for inducing and maintaining remission of refractory polyarteritis nodosa (PAN). Three patients with refractory PAN defined according to the American College of Rheumatology criteria were treated with TCZ infusions (8 mg/kg) on a monthly basis. All of them had severe cutaneous and articular involvement with elevated biological inflammatory markers. One suffered from a neuritis multiplex and one from renal and digestive damage. All three patients were dependent on high doses of glucocorticoids (above 0.5 mg/kg) and two of them were resistant to immunosuppressive drugs. All patients achieved and maintained clinical response and normalisation of the inflammation acute-phase proteins after a few weeks of treatment with TCZ. Prednisolone could be reduced by an average of 41-13 mg/day. These first case reports suggest that IL-6 blockade using TCZ could be a therapeutic alternative to induce remission in patients with polyarteritis nodosa resistant or intolerant to the reference treatment.

  4. Therapeutic approach to metastatic myelo-lymphoproliferative malignancies in spine

    Directory of Open Access Journals (Sweden)

    Mauricio Dominguez

    2016-02-01

    Full Text Available Introduction Myeloproliferative metastatic tumors (leukemia, multiple myeloma and lymphoma are a problem that the spinal surgeon faces increasingly due to longer survival periods associated with their slower growth rates and improved oncological treatments available.Currently there is not consensus about any classifications that establish a prognosis and a treatment plan for the management of these pathologiesObjectiveTo apply and evaluate specific survival scale (ECOG and SCMMM and treatment (Sins for this type of spinal metastases. Material and MethodsPatients with diagnosis of metastatic spine myeloproliferative diseases had the above scale applied and also adding visual analog scale (VAS and Oswestry (ODI to quantify the evolution of treatment. Were included in this sample 5 patients with a minimum follow up of 6 months. ResultsOf the patients sampled 4 patients had a diagnosis of multiple myeloma and one a diagnosis of leukemia, 2 were operated and 3 were treated with radiotherapy, chemotherapy and corset; all improved EVA and Oswestry except one who died at 7 days by an extraspinal complication. ConclusionThe scales used are very useful for therapeutic decision of these patients to be more specific for these metastases.

  5. Molecular approaches to potentiate cisplatin responsiveness in carcinoma therapeutics.

    Science.gov (United States)

    Jain, Aayushi; Jahagirdar, Devashree; Nilendu, Pritish; Sharma, Nilesh Kumar

    2017-09-01

    Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma. We begin with problems associated with cisplatin drugs and current avenues such as depicting molecular modulation of enhanced influx and reduced efflux. We also discuss the scope of the DNA damage response landscape and contribution of regulatory small RNAs towards potentiation of cisplatin responses. Expert commentary: The extensive use of cisplatin and incessant high drug dose have prompted the scientific community to limit the burden of cisplatin without compromising therapeutic success. Currently, there are reports on the potential use of other non-toxic small molecule inhibitors, interference RNAs and peptide mimetics to get rid of cellular adversities responsible for cisplatin resistance and high dose effects.

  6. Bleeding in trauma: Current diagnostic and therapeutic approach

    Directory of Open Access Journals (Sweden)

    Karamarković Aleksandar R.

    2011-01-01

    Full Text Available Recognising shock due to haemorrhage in trauma patients is about constructing a synthesis of trauma mechanism, injuries, vital signs and the therapeutic response of the patient. The treatment of bleeding patients who have exsanguinating injuries is aimed at two major goals: stopping the bleeding and restoration of the blood volume with correct coagulation. Abdominal ultrasound has replaced diagnostic peritoneal lavage for detection of haemoperitoneum. With the development of multi-sliding computer tomography, rapid evaluation by CT-scanning of the trauma patient is possible during resuscitation. The concept of damage control surgery with 'blind' transfusion or 'damage control resuscitation' in treatment of severe trauma, has proven to be of vital importance in the treatment of exsanguinating trauma patients and is adopted worldwide. Pharmacotherapeutic interventions may be a promising concept to limit blood loss after trauma. The role of thromboelastography as point-of-care test for coagulation in massive blood loss is emerging, providing information about actual clot formation and clot stability, shortly after the blood sample is taken.

  7. [Self-selection processes in the choice of the therapeutic training approach: differences in therapeutic attitudes, personality traits and attributional complexity].

    Science.gov (United States)

    Taubner, Svenja; Munder, Thomas; Möller, Heidi; Hanke, Wiebke; Klasen, Jennifer

    2014-06-01

    Treatment approaches differ to a great extent in terms of basic psychological assumptions and practical procedures. This creates questions about the fitting of therapist and therapeutic approach. This paper examines the influence of therapeutic attitudes, mentalization interest and personality traits on the decision for an approach. 184 participants of training programs in one of the 3 licensed treatment approaches in Germany were examined with questionnaires at the beginning of their training. Participants significantly differed in terms of therapeutic attitudes and the metallization interest but not in personality traits except openness. Satisfaction with training was not related to the individual fit of participants to the therapeutic attitudes typical for their approach. Therapeutic attitudes, the extent of mentalization interest, and openness may play a role in self-selection processes in the choice of the approach. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Novel therapeutic delivery approaches in development for pediatric gliomas.

    Science.gov (United States)

    Warren, Katherine E

    2013-09-01

    Pediatric gliomas are a heterogeneous group of diseases, ranging from relatively benign pilocytic astrocytomas with >90% 5-year survival, to glioblastomas and diffuse intrinsic pontine gliomas with low-grade gliomas, but many high-grade tumors are resistant to chemotherapy. A major obstacle and contributor to this resistance is the blood–brain barrier, which protects the CNS by limiting entry of potential toxins, including chemotherapeutic agents. Several novel delivery approaches that circumvent the blood–brain barrier have been developed, including some currently in clinical trials. This review describes several of these novel approaches to improve delivery of chemotherapeutic agents to their site of action at the tumor, in attempts to improve their efficacy and the prognosis of children with this disease.

  9. Cell based therapeutic approach in vascular surgery: application and review

    Directory of Open Access Journals (Sweden)

    Rocca Aldo

    2017-10-01

    Full Text Available Multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from different sources like vascular wall are intensely studied to try to rapidly translate their discovered features from bench to bedside. Vascular wall resident stem cells recruitment, differentiation, survival, proliferation, growth factor production, and signaling pathways transduced were analyzed. We studied biological properties of vascular resident stem cells and explored the relationship from several factors as Matrix Metalloproteinases (MMPs and regulations of biological, translational and clinical features of these cells. In this review we described a translational and clinical approach to Adult Vascular Wall Resident Multipotent Vascular Stem Cells (VW-SCs and reported their involvement in alternative clinical approach as cells based therapy in vascular disease like arterial aneurysms or peripheral arterial obstructive disease.

  10. Reward-Induced Eating: Therapeutic Approaches to Addressing Food Cravings.

    Science.gov (United States)

    Rebello, Candida J; Greenway, Frank L

    2016-11-01

    The homeostatic controls over eating are inextricably linked to the reward aspects of eating. The result is an integrated response that coordinates the internal milieu with the prevailing environment. Thus, appetite, which reflects a complex interaction among the external environment, behavioral profile, and subjective states as well as the storage and metabolism of energy, has an important role in the regulation of energy balance. In the prevailing food environment which offers an abundance of food choices it is likely that the motivation to consume from a wide range of delectable foods plays a greater role in contributing to overeating than in the past when the motivation to eat was largely governed by metabolic need. The response to food-related cues can promote strong desires to eat known as cravings by activating the mesocorticolimbic dopamine neurocircuitry. Cravings are associated with subsequent eating and weight-related outcomes. Being able to control food cravings is a determinant of success at adhering to an energy-restricted diet regimen. Increased understanding of the neurocircuitry of appetite regulation, especially reward-related eating behavior, has provided potential targets for therapeutic anti-obesity agents specifically directed at reward mechanisms. The naltrexone-bupropion combination and lorcaserin, which are both approved by the US Food and Drug Administration (FDA) for long-term weight management, have shown promise in addressing craving-related eating behavior. Phentermine and liraglutide are approved as monotherapies for weight management. Preliminary research suggests that liraglutide, as well as phentermine alone or in combination with lorcaserin, may be effective in targeting food cravings. Food components such as thylakoid membranes have also been shown to influence food cravings. This review explores the concepts related to appetite and reward-induced eating behavior, as well as the pharmacological options and food-derived components

  11. Therapeutic issues in vascular dementia: studies, designs and approaches.

    Science.gov (United States)

    Black, Sandra E

    2007-03-01

    Vascular dementia (VaD) is a heterogeneous disorder resulting from various cerebrovascular diseases (CVD) causing cognitive impairment that reflects severity and location of damage. Epidemiological studies suggest VaD is the second commonest cause of dementia, but autopsy series report that pure VaD is infrequent, while combined CVD and Alzheimer's Disease(AD) is likely the commonest pathological-dementia correlate. Both diseases share vascular risk factors and benefit from their treatment. The most widely used diagnostic criteria for VaD are highly specific but not sensitive. Vascular Cognitive Impairment (VCI) is a dynamic, evolving concept that embraces VaD, Vascular Cognitive Impairment No Dementia (VCIND) and mixed AD and CVD. Clinical trials to date have focused on probable and possible VaD with beneficial effects evident for different drug classes, including cholinergic agents and NMDA agonists. Limitations have included use of cognitive tools suitable for AD that are insensitive to executive dysfunction. Disease heterogeneity has not been adequately controlled and subtypes require further study. Diagnostic VaD criteria now 13 years old need updating. More homogeneous subgroups need to be defined and therapeutically targeted to improve cognitive-behavioural outcomes including optimal control of vascular risk factors. More sensitive testing of executive function outlined in recent VCI Harmonization criteria and longer trial duration are needed to discern meaningful effects. Imaging criteria must be well-defined, with centralized review and standardized protocols. Serial scanning with quantification of tissue atrophy and lesion burden is becoming feasible, and cognitive interventions, including rehabilitation pharmacotherapy, with drugs strategically coupled to cognitive -behavioural treatments, hold promise and need further development.

  12. Late-Developing Supernumerary Premolars: Analysis of Different Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Sergio Paduano

    2016-01-01

    Full Text Available This case series describes the different potential approaches to late-developing supernumerary premolars (LDSP. LDSP are supernumerary teeth (ST formed after the eruption of the permanent dentition; usually they develop in the premolar region of the upper and lower jaw. The choice to extract or to monitor the LDSP depends on many factors and has to be carefully planned due to the several risks that either the monitoring or the extraction could provoke. These four cases of LDSP showed different treatment plan alternatives derived from a scrupulous assessment of the clinical and radiographic information.

  13. Caloric intake and Alzheimer's disease. Experimental approaches and therapeutic implications.

    Science.gov (United States)

    Pasinetti, Giulio Maria; Zhao, Zhong; Qin, Weiping; Ho, Lap; Shrishailam, Yemul; Macgrogan, Donal; Ressmann, Wendy; Humala, Nelson; Liu, Xunxian; Romero, Carmen; Stetka, Breton; Chen, Linghong; Ksiezak-Reding, Hanna; Wang, Jun

    2007-01-01

    through which dietary restriction may beneficially influence AD neuropathology and the eventual discovery of future "mimetics" capable of anti-Beta-amyloidogenic activity will help in the development of "lifestyle therapeutic strategies" in AD and possibly other neurodegenerative disorders.

  14. Phantom limb pain: cortical plasticity and novel therapeutic approaches.

    Science.gov (United States)

    Flor, H; Birbaumer, N

    2000-10-01

    Phantom limb pain is still a very frequent consequence of peripheral deafferentation or amputation of a limb. Recent findings from animal and neuroimaging studies suggest that phantom limb pain might be a central phenomenon, related to changes in the cortical, thalamic and spinal representation of the painful limb, and might be a type of somatosensory pain memory. Based on these assumptions, new treatment approaches focus on sensory discrimination training or motor cortex stimulation in an effort to influence cortical reorganization. Prevention of perpetuation of a somatosensory pain memory might also be possible through pharmacological agents such as N-methyl-D-aspartate antagonists and gamma-aminobutyric acid agonists, substances that have been shown to influence and prevent cortical reorganization.

  15. Proteomic approaches and identification of novel therapeutic targets for alcoholism.

    Science.gov (United States)

    Gorini, Giorgio; Harris, R Adron; Mayfield, R Dayne

    2014-01-01

    Recent studies have shown that gene regulation is far more complex than previously believed and does not completely explain changes at the protein level. Therefore, the direct study of the proteome, considerably different in both complexity and dynamicity to the genome/transcriptome, has provided unique insights to an increasing number of researchers. During the past decade, extraordinary advances in proteomic techniques have changed the way we can analyze the composition, regulation, and function of protein complexes and pathways underlying altered neurobiological conditions. When combined with complementary approaches, these advances provide the contextual information for decoding large data sets into meaningful biologically adaptive processes. Neuroproteomics offers potential breakthroughs in the field of alcohol research by leading to a deeper understanding of how alcohol globally affects protein structure, function, interactions, and networks. The wealth of information gained from these advances can help pinpoint relevant biomarkers for early diagnosis and improved prognosis of alcoholism and identify future pharmacological targets for the treatment of this addiction.

  16. Upper GI Disorders: Pathophysiology and Current Therapeutic Approaches.

    Science.gov (United States)

    Parkman, Henry P

    2017-01-01

    Symptoms referable to the upper digestive tract are associated with abnormalities of upper gastric neuromuscular function including abnormalities of motility, sensation, and absorption. Of the upper digestive tract, the stomach is of particular importance in its role in symptom generation and is highlighted in this chapter. Gastric symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical activity and contractility. Treatment of gastric neuromuscular disorders requires an understanding of pathophysiology of the disorders, the appropriate use and interpretation of diagnostic tests, and the knowledge of effective treatment options. This chapter covers the pathophysiology and current treatment approaches to disorders of the upper gastrointestinal tract, focusing on classic disorders of the stomach, particularly gastroparesis and functional dyspepsia.

  17. Therapeutic Approach to Cystic Neoplasms of the Pancreas

    Science.gov (United States)

    Al Efishat, Mohammad; Allen, Peter J

    2016-01-01

    Given the widespread use of high quality cross-sectional imaging, cystic lesions of the pancreas are being diagnosed more frequently. Management of these lesions is challenging as it largely depends on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions, however the accuracy of these tests is limited, and unable to predict malignancy with certainty. While asymptomatic serous cystadenomas (SCA) can be managed conservatively, mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) are more difficult to manage given their variable potential for malignancy. A selective approach, based on the preoperative likelihood of high-grade dysplasia or invasive disease, is now the standard of care. Current research is focusing on the development of pre-operative markers for discriminating between histopathologic sub-types, and for identifying the degree of dysplasia in patients with precancerous mucinous lesions. Improvements in these diagnostic tools will hopefully limit resection to patients with high-risk lesions, and spare patients with low-risk or benign lesions the risks of pancreatectomy. PMID:27013369

  18. 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.

  19. Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis.

    Science.gov (United States)

    Kumar, L Dinesh; Karthik, R; Gayathri, N; Sivasudha, T

    2016-04-01

    This review is intended to provide a summary of the pathogenesis, diagnosis and therapies for rheumatoid arthritis. Rheumatoid arthritis (RA) is a common form of inflammatory autoimmune disease with unknown aetiology. Bone degradation, cartilage and synovial destruction are three major pathways of RA pathology. Sentinel cells includes dendritic cells, macrophages and mast cells bound with the auto antigens and initiate the inflammation of the joints. Those cells further activates the immune cells on synovial membrane by releasing inflammatory cytokines Interleukin 1, 6, 17, etc., Diagnosis of this disease is a combinational approach comprises radiological imaging, blood and serology markers assessment. The treatment of RA still remain inadequate due to the lack of knowledge in disease development. Non-steroidal anti-inflammatory drugs, disease modifying anti rheumatic drugs and corticosteroid are the commercial drugs to reduce pain, swelling and suppressing several disease factors. Arthroscopy will be an useful method while severe degradation of joint tissues. Gene therapy is a major advancement in RA. Suppressor gene locus of inflammatory mediators and matrix degrading enzymes were inserted into the affected area to reduce the disease progression. To overcome the issues aroused from those therapies like side effects and expenses, phytocompounds have been investigated and certain compounds are proved for their anti-arthritic potential. Furthermore certain complementary alternative therapies like yoga, acupuncture, massage therapy and tai chi have also been proved for their capability in RA treatment. Copyright © 2016. Published by Elsevier Masson SAS.

  20. 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.

  1. Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Attila eSzabo

    2015-07-01

    Full Text Available Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation and cell survival via activating NF-κB and MAPKs. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT, lysergic acid diethylamide (LSD, 2,5-dimethoxy-4-iodoamphetamine (DOI and 3,4-methylenedioxy-methamphetamine (MDMA will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with Toll-like and RIG-I-like pattern recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression and Alzheimer's disease.

  2. Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities.

    Science.gov (United States)

    Szabo, Attila

    2015-01-01

    Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer's disease.

  3. 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

  4. [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.

  5. A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion

    OpenAIRE

    Jiang, Wenlei; Makhlouf, Fairouz; Schuirmann, Donald J.; Zhang, Xinyuan; Zheng, Nan; Conner, Dale; Yu, Lawrence X.; Lionberger, Robert

    2015-01-01

    Various health communities have expressed concerns regarding whether average bioequivalence (BE) limits (80.00–125.00%) for the 90% confidence interval of the test-to-reference geometric mean ratio are sufficient to ensure therapeutic equivalence between a generic narrow therapeutic index (NTI) drug and its reference listed drug (RLD). Simulations were conducted to investigate the impact of different BE approaches for NTI drugs on study power, including (1) direct tightening of average BE lim...

  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. Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases.

    Science.gov (United States)

    Gabathuler, Reinhard

    2010-01-01

    The central nervous system is protected by barriers which control the entry of compounds into the brain, thereby regulating brain homeostasis. The blood-brain barrier, formed by the endothelial cells of the brain capillaries, restricts access to brain cells of blood-borne compounds and facilitates nutrients essential for normal metabolism to reach brain cells. This very tight regulation of the brain homeostasis results in the inability of some small and large therapeutic compounds to cross the blood-brain barrier (BBB). Therefore, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. In this review, we will address the different approaches used to increase the transport of therapeutics from blood into the brain parenchyma. We will mainly concentrate on the physiologic approach which takes advantage of specific receptors already expressed on the capillary endothelial cells forming the BBB and necessary for the survival of brain cells. Among all the approaches used for increasing brain delivery of therapeutics, the most accepted method is the use of the physiological approach which takes advantage of the transcytosis capacity of specific receptors expressed at the BBB. The low density lipoprotein receptor related protein (LRP) is the most adapted for such use with the engineered peptide compound (EPiC) platform incorporating the Angiopep peptide in new therapeutics the most advanced with promising data in the clinic.

  8. 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.

  9. Review of Diagnostic and Therapeutic Approach to Canine Myxomatous Mitral Valve Disease

    Science.gov (United States)

    Borgarelli, Michele

    2017-01-01

    The most common heart disease that affects dogs is myxomatous mitral valve disease. In this article, we review the current diagnostic and therapeutic approaches to this disease, and we also present some of the latest technological advancements in this field. PMID:29056705

  10. [Depression in children and adolescents: prevalence, diagnosis, etiology, gender differences and therapeutic approaches].

    Science.gov (United States)

    Seiffge-Krenke, Inge

    2007-01-01

    Prevalence rates of the different forms of depression (depressive mood, depressive syndromes and Major Depression) have increased during recent years. Similarily, gender differences have augmented. Stress, dysfunctional coping styles, a negative body image, and an insecure attachment style have been identified as factors contributing to the etiology of depression. Different therapeutic approaches were presented with psychonanalytic treatment being the most comprehensive.

  11. 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.

  12. 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.

  13. Combinatorial therapeutic approaches with RNAi and anticancer drugs using nanodrug delivery systems.

    Science.gov (United States)

    Babu, Anish; Munshi, Anupama; Ramesh, Rajagopal

    2017-09-01

    RNA interference (RNAi) is emerging as a powerful approach in cancer treatment. siRNA is an important RNAi tool that can be designed to specifically silence the expression of genes involved in drug resistance and chemotherapeutic inactivity. Combining siRNA and other therapeutic agents can overcome the multidrug resistance (MDR) phenomenon by simultaneously silencing genes and enhancing chemotherapeutic activity. Moreover, the therapeutic efficiency of anticancer drugs can be significantly improved by additive or synergistic effects induced by siRNA and combined therapies. Co-delivery of these diverse anticancer agents, however, requires specially designed nanocarriers. This review highlights the recent trends in siRNA/anticancer drug co-delivery systems under the major categories of liposomes/lipid, polymeric and inorganic nanoplatforms. The objective is to discuss the strategies for nanocarrier-based co-delivery systems using siRNA/anticancer drug combinations, emphasizing various siRNA targets that help overcome MDR and enhance therapeutic efficiency.

  14. The U.S. Department of Education's "Race-Neutral Alternatives in Postsecondary Education: Innovative Approaches to Diversity"--Are They Viable Substitutes for Affirmative Action?

    Science.gov (United States)

    Commission on Civil Rights, Washington, DC.

    On March 28, 2003 the U.S. Department of Education (ED) issued a report titled "Race-Neutral Alternatives in Postsecondary Education: Innovative Approaches to Diversity." The purpose of this report is to describe a number of race-neutral approaches that postsecondary institutions across the United States are using. This staff assessment by the…

  15. Viable But Not Culturable (VBNC) state of Brettanomyces bruxellensis in wine: New insights on molecular basis of VBNC behaviour using a transcriptomic approach.

    Science.gov (United States)

    Capozzi, Vittorio; Di Toro, Maria Rosaria; Grieco, Francesco; Michelotti, Vania; Salma, Mohammad; Lamontanara, Antonella; Russo, Pasquale; Orrù, Luigi; Alexandre, Hervé; Spano, Giuseppe

    2016-10-01

    The spoilage potential of Brettanomyces bruxellensis in wine is strongly connected with the aptitude of this yeast to enter in a Viable But Non Culturable (VBNC) state when exposed to the harsh wine conditions. In this work, we characterized the VBNC behaviour of seven strains of B. bruxellensis representing a regional intraspecific biodiversity, reporting conclusive evidence for the assessment of VBNC as a strain-dependent character. The VBNC behaviour was monitored by fluorescein diacetate staining/flow cytometry for eleven days after addition of 0.4, 0.6, 0.8, 1 and 1.2 mg/L of molecular SO2 (entrance in the VBNC state) and after SO2 removal (exit from the VBNC state). Furthermore, one representative strain was selected and RNA-seq analysis performed after exposure to 1.2 mg/L SO2 and during the recovery phase. 30 and 1634 genes were identified as differentially expressed following VBNC entrance and 'resuscitation', respectively. The results reported strongly suggested that the entrance in the SO2-induced VBNC state in B. bruxellensis is associated with both, sulfite toxicity and oxidative stress response, confirming the crucial role of genes/proteins involved in redox cell homeostasis. Among the genes induced during recovery, the expression of genes involved in carbohydrate metabolism and encoding heat shock proteins, as well as enriched categories including amino acid transport and transporter activity was observed. The evidences of a general repression of genes involved in DNA replication suggest the occurrence of a true resuscitation of cell rather than a simple regrowth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Novel activity-dependent approaches to therapeutic hypnosis and psychotherapy: the general waking trance.

    Science.gov (United States)

    Rossi, Ernest; Erickson-Klein, Roxanna; Rossi, Kathryn

    2008-10-01

    This paper presents a highly edited version of a videotape made in 1980 by Marion Moore, M.D., showing Milton H. Erickson and Moore demonstrating novel, activity-dependent approaches to hand-levitation and therapeutic hypnosis on their subject, Ernest Rossi. Erickson's naturalistic and utilization approach is described in his very direct and surprising induction in a trance challenged patient. These novel, and surprising inductions are examples of how Erickson was prescient in developing activity-dependent approaches to therapeutic hypnosis and psychotherapy several generations before modern neuroscience documented the activity-dependent molecular-genomic mechanisms of memory, learning, and behavior change. Erickson describes a case where he utilized what he called, "The General Waking Trance" when he "dared" not use an obvious hypnotic induction. It is proposed that the states of intense mental absorption and response attentiveness that are facilitated by the general waking trance are functionally related to the three conditions neuroscientists have identified as novelty, enrichment, and exercise (both mental and physical), which can turn on activity-dependent gene expression and activity-dependent brain plasticity, that are the molecular-genomic and neural basis ofmemory, learning, consciousness, and behavior change. We recommend that the next step in investigating the efficacy of therapeutic hypnosis will be in partnering with neuroscientists to explore the possibilities and limitations of utilizing the activity-dependent approaches to hypnotic induction and the general waking trance in facilitating activity-dependent gene expression and brain plasticity.

  17. 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.

  18. Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

    Science.gov (United States)

    Llorens-Martín, María; Hernández, Félix; Avila, Jesús

    2013-01-01

    Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field. PMID:23690659

  19. Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials.

    Science.gov (United States)

    Shimizu-Motohashi, Yuko; Miyatake, Shouta; Komaki, Hirofumi; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative muscle disorder caused by the absence of dystrophin. There is no curative therapy, although innovative therapeutic approaches have been aggressively investigated over recent years. Currently, the international clinical trial registry platform for this disease has been constructed and clinical trials for innovative therapeutic approaches are underway. Among these, exon skipping and read-through of nonsense mutations are in the most advanced stages, with exon skipping theoretically applicable to a larger number of patients. To date, exon skipping that targets exons 51, 44, 45, and 53 is being globally investigated including in USA, EU, and Japan. The latest announcement from Japan was made, demonstrating successful dystrophin production in muscles of patients with DMD after treating with exon 53 skipping antisense oligonucleotides (ASOs). However, the innovative therapeutic approaches have demonstrated limited efficacy. To address this issue in exon skipping, studies to unveil the mechanism underlying gymnotic delivery of ASO uptake in living cells have been conducted in an effort to improve in vivo delivery. Further, establishing the infrastructures to integrate multi-institutional clinical trials are needed to facilitate the development of successful therapies for DMD, which ultimately is applicable to other myopathies and neurodegenerative diseases, including spinal muscular atrophy and motor neuron diseases.

  20. Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and future.

    Science.gov (United States)

    de la Torre, Rafael; Dierssen, Mara

    2012-01-01

    Clinical trials with drugs aimed at treatment of Alzheimer disease to decelerate cognitive decline and translated mimetically to demented and young nondemented Down syndrome patients have been unable to demonstrate improvements in cognitive performance and functioning. Unfortunately, results from clinical trials do not support the use of NMDA antagonists like memantine and we should await at the development of safer GABA(A) antagonists to conclude about the efficacy of approaching Down syndrome therapeutics by modulating neurotransmission systems altered in this pathology. The use of folinic acid or antioxidants in DS patients is not supported by scientific evidence and do not provide improvement in cognitive performance to patients. Alternatively to the modulation of neurotransmission systems, future therapeutic approaches should focus at normalizing the expression levels or function of candidate molecules. Epigallocatechin gallate, a green tea polyphenol, that modulates DYRK1A functioning has already shown preliminarily that this approach may prove useful in therapeutics. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Therapeutics for filovirus infection: traditional approaches and progress towards in silico drug design.

    Science.gov (United States)

    Shurtleff, Amy C; Nguyen, Tam L; Kingery, David A; Bavari, Sina

    2012-10-01

    Ebolaviruses and marburgviruses cause severe and often lethal human hemorrhagic fevers. As no FDA-approved therapeutics are available for these infections, efforts to discover new therapeutics are important, especially because these pathogens are considered biothreats and emerging infectious diseases. All methods for discovering new therapeutics should be considered, including compound library screening in vitro against virus and in silico structure-based drug design, where possible, if sufficient biochemical and structural information is available. This review covers the structure and function of filovirus proteins, as they have been reported to date, as well as some of the current antiviral screening approaches. The authors discuss key studies mapping small-molecule modulators that were found through library and in silico screens to potential sites on viral proteins or host proteins involved in virus trafficking and pathogenesis. A description of ebolavirus and marburgvirus diseases and available animal models is also presented. To discover novel therapeutics with potent efficacy using sophisticated computational methods, more high-resolution crystal structures of filovirus proteins and more details about the protein functions and host interaction will be required. Current compound screening efforts are finding active antiviral compounds, but an emphasis on discovery research to investigate protein structures and functions enabling in silico drug design would provide another avenue for finding antiviral molecules. Additionally, targeting of protein-protein interactions may be a future avenue for drug discovery since disrupting catalytic sites may not be possible for all proteins.

  2. Therapeutic Approaches for Preserving or Restoring Pancreatic β-Cell Function and Mass

    Directory of Open Access Journals (Sweden)

    Kyong Yeun Jung

    2014-12-01

    Full Text Available The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in β-cell function and delay the progression of disease. Pancreatic β-cell dysfunction and decreased β-cell mass are crucial in the development of diabetes. The β-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic β-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, β-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional β-cell mass. In this context, therapeutic approaches designed to increase β-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various β-cell defects that appear in patients with diabetes and outline the mechanisms of β-cell failure. We also review common methods for assessing β-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve β-cell function and increase β-cell mass.

  3. Teaching communication and therapeutic relationship skills to baccalaureate nursing students: a peer mentorship simulation approach.

    Science.gov (United States)

    Miles, Leslie W; Mabey, Linda; Leggett, Sarah; Stansfield, Katie

    2014-10-01

    The literature on techniques for improving student competency in therapeutic communication and interpersonal skills is limited. A simulation approach to enhance the learning of communication skills was developed to address these issues. Second-semester and senior nursing students participated in videorecorded standardized patient simulations, with senior students portraying the patient. Following simulated interactions, senior students provided feedback to junior students on their use of communication skills and other therapeutic factors. To integrate the learning experience, junior students completed a written assignment, in which they identified effective and noneffective communication; personal strengths and weaknesses; and use of genuineness, empathy, and positive regard. A videorecording of each student interaction gave faculty the opportunity to provide formative feedback to students. Student evaluations have been positive. Themes identified in student evaluations include the impact of seeing oneself, significance of practicing, getting below the surface in communication, and moving from insight to goal setting. Copyright 2014, SLACK Incorporated.

  4. Diabetes mellitus-associated vascular impairment: novel circulating biomarkers and therapeutic approaches.

    Science.gov (United States)

    Tousoulis, Dimitris; Papageorgiou, Nikolaos; Androulakis, Emmanuel; Siasos, Gerasimos; Latsios, George; Tentolouris, Konstantinos; Stefanadis, Christodoulos

    2013-08-20

    It is widely accepted that diabetes mellitus (DM) impairs endothelial nitric oxide synthase activity as well as enhances the production of reactive oxygen species, thus resulting in diminished nitric oxide bioavailability and the consequent pro-atherogenetic alterations. Important biomarkers of the vasculature are related to endothelial dysfunction, to inflammatory and coagulation processes, and to oxidative stress in DM. Several therapeutic strategies might exert favorable effects on the vasculature of diabetic patients, such as insulin analogues, antihypertensive agents, statins, and hypoglycemic agents, whereas in spite of the prominent role of oxidative stress in diabetes, antioxidant therapy remains controversial. The use of specific biomarkers related to vascular function could be a useful therapeutic approach in such patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. Multiple, sclerosis: clinical feature, pathogenesis and current therapeutical approaches; Encephalomyelitis disseminata: Klinik, Pathogenese und aktuelle Therapiekonzepte

    Energy Technology Data Exchange (ETDEWEB)

    Merkelbach, S.; Koelmel, C.; Schimrigk, K. [Universitaet des Saarlandes, Homburg/Saar (Germany). Neurologische Klinik

    2000-11-01

    Multiple sclerosis (MS) is considered as a T-cell mediated autoimmune disease. Caused by central nervous system demyelination and axonal damage varying clinical signs do occur either with relapsing-remitting or with chronic progressive course. Based on pathogenetic considerations immunomodulative and immunosuppressive therapeutical approaches are used to limit the disease progression. Clinical symptoms, diagnostic criteria, pathogenetical considerations, and consecutive therapeutical interventions are summarized. (orig.) [German] Die Encephalomyelitis disseminata oder Multiple Sklerose (ED oder MS) gilt als T-Zell-vermittelte Autoimmunerkrankung. Schubfoermig oder chronisch progredient kommt es im Zentralnervensystem infolge einer Demyelinisierung der weissen Substanz und axonaler Schaedigungen zu einer Vielzahl neurologischer Symptome. Basierend auf pathogenetischen Erkenntnissen werden derzeit immunmodulative und immunsuppressive Therapien eingesetzt, die den Krankheitsverlauf zumindest bremsen. Klinische Symptome, diagnostische Kriterien, pathogenetische Ueberlegungen und sich daraus ableitende Therapiekonzepte werden zusammenfassend dargestellt. (orig.)

  7. 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.

  8. Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches

    Science.gov (United States)

    Ali, Liaqat; Goraya, Mohsan Ullah; Arafat, Yasir; Ajmal, Muhammad; Chen, Ji-Long; Yu, Daojin

    2017-01-01

    Quorum-sensing systems control major virulence determinants in Enterococcus faecalis, which causes nosocomial infections. The E. faecalis quorum-sensing systems include several virulence factors that are regulated by the cytolysin operon, which encodes the cytolysin toxin. In addition, the E. faecalis Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models. Therefore, there is substantial interest in understanding and targeting these regulatory pathways to develop novel therapies for enterococcal infection control. Quorum-sensing inhibitors could be potential therapeutic agents for attenuating the pathogenic effects of E. faecalis. Here, we discuss the regulation of cytolysin, the LuxS system, and the Fsr system, their role in E. faecalis-mediated infections, and possible therapeutic approaches to prevent E. faecalis infection. PMID:28467378

  9. Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies.

    Science.gov (United States)

    Mueller, Alan J; Peffers, Mandy J; Proctor, Carole J; Clegg, Peter D

    2017-08-01

    Systems orientated research offers the possibility of identifying novel therapeutic targets and relevant diagnostic markers for complex diseases such as osteoarthritis. This review demonstrates that the osteoarthritis research community has been slow to incorporate systems orientated approaches into research studies, although a number of key studies reveal novel insights into the regulatory mechanisms that contribute both to joint tissue homeostasis and its dysfunction. The review introduces both top-down and bottom-up approaches employed in the study of osteoarthritis. A holistic and multiscale approach, where clinical measurements may predict dysregulation and progression of joint degeneration, should be a key objective in future research. The review concludes with suggestions for further research and emerging trends not least of which is the coupled development of diagnostic tests and therapeutics as part of a concerted effort by the osteoarthritis research community to meet clinical needs. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1573-1588, 2017. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

  10. Exergaming as a viable therapeutic tool to improve static and dynamic balance among older adults and people with idiopathic Parkinson’s disease: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Dale Michael Harris

    2015-09-01

    Full Text Available The use of virtual reality games (known as ‘exergaming’ as a neurorehabilitation tool is gaining interest. Therefore, we aim to collate evidence for the effects of exergaming on the balance and postural control of older adults and people with idiopathic Parkinson’s disease (IPD. Six electronic databases were searched, from inception to April 2015, to identify relevant studies. Standardised mean differences (SMD and 95% confidence intervals (CI were used to calculate effect sizes between experimental and control groups. I2 statistics were used to determine levels of heterogeneity. 309 older adults and 74 people with IPD were assessed across eleven studies. The results showed that exergaming improved static balance (SMD 1.069, 95% CI 0.563 to 1.576, postural control (SMD 0.826, 95% CI 0.481 to 1.170 and dynamic balance (SMD -0.808, 95% CI -1.192 to -0.424 in healthy older adults. Two PD studies showed an improvement in static balance (SMD 0.124, 95% CI -0.581 to 0.828 and postural control (SMD 2.576, 95% CI 1.534 to 3.599. Our findings suggest that exergaming might be an appropriate therapeutic tool for improving balance and postural control in older adults, but more large-scale trials are needed to determine if the same is true for people with IPD.

  11. Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases

    Directory of Open Access Journals (Sweden)

    Ka-To Shum

    2013-11-01

    Full Text Available Viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. Many life-threatening diseases, such as AIDS, SARS, hepatitis and some cancers, are caused by viruses. Because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. One approach that has recently received much attention is aptamer-based therapeutics. Aptamer technology has high target specificity and versatility, i.e., any viral proteins could potentially be targeted. Consequently, new aptamer-based therapeutics have the potential to lead a revolution in the development of anti-infective drugs. Additionally, aptamers can potentially bind any targets and any pathogen that is theoretically amenable to rapid targeting, making aptamers invaluable tools for treating a wide range of diseases. This review will provide a broad, comprehensive overview of viral therapies that use aptamers. The aptamer selection process will be described, followed by an explanation of the potential for treating virus infection by aptamers. Recent progress and prospective use of aptamers against a large variety of human viruses, such as HIV-1, HCV, HBV, SCoV, Rabies virus, HPV, HSV and influenza virus, with particular focus on clinical development of aptamers will also be described. Finally, we will discuss the challenges of advancing antiviral aptamer therapeutics and prospects for future success.

  12. 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…

  13. A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion.

    Science.gov (United States)

    Jiang, Wenlei; Makhlouf, Fairouz; Schuirmann, Donald J; Zhang, Xinyuan; Zheng, Nan; Conner, Dale; Yu, Lawrence X; Lionberger, Robert

    2015-07-01

    Various health communities have expressed concerns regarding whether average bioequivalence (BE) limits (80.00-125.00%) for the 90% confidence interval of the test-to-reference geometric mean ratio are sufficient to ensure therapeutic equivalence between a generic narrow therapeutic index (NTI) drug and its reference listed drug (RLD). Simulations were conducted to investigate the impact of different BE approaches for NTI drugs on study power, including (1) direct tightening of average BE limits and (2) a scaled average BE approach where BE limits are tightened based on the RLD's within-subject variability. Addition of a variability comparison (using a one-tailed F test) increased the difficulty for generic NTIs more variable than their corresponding RLDs to demonstrate bioequivalence. Based on these results, the authors evaluate the fully replicated, 2-sequence, 2-treatment, 4-period crossover study design for NTI drugs where the test product demonstrates BE based on a scaled average bioequivalence criterion and a within-subject variability comparison criterion.

  14. Diagnostic and therapeutic approach of congenital solitary coronary artery fistulas in adults : Dutch case series and review of literature

    NARCIS (Netherlands)

    Said, S. A. M.; Nijhuis, R. L. G.; op den Akker, Jeroen; Kimman, G. P.; Van Houwelingen, K. G.; Gerrits, D.; Huisman, A. B.; Slart, R. H. J. A.; Nicastia, D. M.; Koomen, E. M.; Tans, A. C.; Al-Windy, N. Y. Y.; Sonker, U.; Slagboom, T.; Pronk, A. C. B.

    Background Coronary artery fistulas (CAFs) are infrequent anomalies, coincidentally detected during coronary angiography (CAG). Aim To elucidate the currently used diagnostic imaging modalities and applied therapeutic approaches. Materials and Methods Five Dutch patients were found to have CAFs. A

  15. The role of growth factors as a therapeutic approach to demyelinating disease

    Science.gov (United States)

    Huang, Yangyang; Dreyfus, Cheryl F.

    2016-01-01

    A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions. This review focuses on five such proteins that are present in the lesion site and impact oligodendrocyte regeneration. It then presents approaches that are being exploited to manipulate the lesion environment affiliated with multiple neurodegenerative diseases and suggests that the utility of these approaches can extend to demyelination. Challenges are to further understand the roles of specific growth factors on a cellular and tissue level. Emerging technologies can then be employed to optimize the use of growth factors to ameliorate the deficits associated with demyelinating degenerative diseases. PMID:27016070

  16. The role of growth factors as a therapeutic approach to demyelinating disease.

    Science.gov (United States)

    Huang, Yangyang; Dreyfus, Cheryl F

    2016-09-01

    A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions such as are evident in Multiple Sclerosis (MS). This review focuses on five such proteins that are present in the lesion site and impact oligodendrocyte regeneration. It then presents approaches that are being exploited to manipulate the lesion environment affiliated with multiple neurodegenerative diseases and suggests that the utility of these approaches can extend to demyelination. Challenges are to further understand the roles of specific growth factors on a cellular and tissue level. Emerging technologies can then be employed to optimize the use of growth factors to ameliorate the deficits associated with demyelinating degenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

    Science.gov (United States)

    Sahu, Praveen K.; Satpathi, Sanghamitra; Behera, Prativa K.; Mishra, Saroj K.; Mohanty, Sanjib; Wassmer, Samuel Crocodile

    2015-01-01

    Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively. PMID:26579500

  18. Resolution of Coccidioides immitis endophthalmitis with an aggressive surgical and medical therapeutic approach.

    Science.gov (United States)

    Reed, David C; Shah, Kayur H; Hubschman, Jean-Pierre

    2013-07-01

    Coccidioides immitis endophthalmitis usually results in enucleation, and there is evidence that vitrectomized eyes are more likely to become enucleated. A 55-year-old man presented to us with steroid-resistant granulomatous uveitis and was eventually diagnosed with C. immitis endophthalmitis. He was treated with an aggressive medical and surgical approach, receiving a total of 16 intravitreal antifungal injections and three vitrectomies, as well as lensectomy and penetrating keratoplasty. At 13 months after presentation, the patient's eye was free of inflammation, and his best corrected visual acuity was 20/25. This is the first reported case of culture-proven C. immitis endophthalmitis with a favorable final outcome. We propose that the good outcome may have been due to our aggressive therapeutic approach.

  19. [The contribution of psychotherapy to a therapeutic approach of bipolar disorders that combines psychotherapy and pharmacotherapy].

    Science.gov (United States)

    Spivacow, Miguel Alejo

    2003-01-01

    The author assumes that genetic and environmental factors interact in the etiology of Bipolar Disorders. The main goal of this article is to discuss the contribution of psychotherapy in a therapeutic approach to Bipolar Disorders that includes both psychopharmacological treatment and psychotherapy. The central tenet of the paper is that the psychotherapeutic approach to depression focuses on the personality structure as a whole and identifies the predominant psychodynamic factors: the disparity between actual and ideal self-representations, the loss of internal objects, the impact of the vicissitudes of symbiotic relationships on the psychic equilibrium. In the treatment of mania, the psychotherapeutic interventions are considered to be significantly less useful than in the treatment of depression.

  20. A prodrug approach to the use of coumarins as potential therapeutics for superficial mycoses.

    Directory of Open Access Journals (Sweden)

    Derry K Mercer

    Full Text Available Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20-25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide, inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones.

  1. Finding the best therapeutic approach for PCOS: the importance of inositol(s) bioavailability.

    Science.gov (United States)

    Orrù, B; Circo, R; Logoteta, P; Petousis, S; Carlomagno, G

    2017-06-01

    Broadening clinical evidence has markedly designated inositol(s) as a common and effective therapeutic approach for PCOS and infertility. Although considerable research has been focused on the use in clinical practice of myo-inositol (myo-ins) and D-chiro-inositol (D-chiro-ins), the two major inositol stereoisomers, less attention has been paid to their bioavailability. Therefore, the aim of this paper is to gather and analyze information on inositol(s) bioavailability, to better delineate its optimal concentration for scientific and clinical purposes. Throughout the search in PubMed, Google Scholar, and ResearchGate we identified only two studies that investigated the pharmacokinetic (PK) profile of different myo-ins administrations. This analysis found no advantage in terms of PK for single 4 g dosing of myo-ins compared to 2 g twice a day, which allowed to get a 24-hour coverage, contrary to the singular dose. Indeed, the differences regarding the area under the curve (AUC) between the two PK profiles are linked only to the maximum concentration (Cmax) but not to the time variable. In conclusion, splitting the therapeutic dosage of 4 g myo-ins in two distinct administrations seems to be the best approach for a full-day coverage.

  2. The potential for targeted rewriting of epigenetic marks in COPD as a new therapeutic approach.

    Science.gov (United States)

    Wu, Dan-Dan; Song, Juan; Bartel, Sabine; Krauss-Etschmann, Susanne; Rots, Marianne G; Hylkema, Machteld N

    2017-08-19

    Chronic obstructive pulmonary disease (COPD) is an age and smoking related progressive, pulmonary disorder presenting with poorly reversible airflow limitation as a result of chronic bronchitis and emphysema. The prevalence, disease burden for the individual, and mortality of COPD continues to increase, whereas no effective treatment strategies are available. For many years now, a combination of bronchodilators and anti-inflammatory corticosteroids has been most widely used for therapeutic management of patients with persistent COPD. However, this approach has had disappointing results as a large number of COPD patients are corticosteroid resistant. In patients with COPD, there is emerging evidence showing aberrant expression of epigenetic marks such as DNA methylation, histone modifications and microRNAs in blood, sputum and lung tissue. Therefore, novel therapeutic approaches may exist using epigenetic therapy. This review aims to describe and summarize current knowledge of aberrant expression of epigenetic marks in COPD. In addition, tools available for restoration of epigenetic marks are described, as well as delivery mechanisms of epigenetic editors to cells. Targeting epigenetic marks might be a very promising tool for treatment and lung regeneration in COPD in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The relationship between sluggish cognitive tempo and burnout symptoms in psychiatrists with different therapeutic approaches.

    Science.gov (United States)

    Gül, Ahmet; Gül, Hesna; Özkal, Ummuhan Ceviz; Kıncır, Zeliha; Gültekin, Gozde; Emul, Hacı Murat

    2017-06-01

    Burnout is a serious problem for psychiatrists that has implications for clinical practice and personal health. While burnout is known to affect cognitive functions, no studies have examined the relationship between sluggish cognitive tempo (SCT) and burnout. This study aimed to examine this relationship and related factors as socio-demographic, occupational environment in psychiatrists. Participants(n=201, aged between 25 and 52 years,57.7% female) completed socio-demographic information form, Maslach Burnout Inventory and SCT Scale. According to our results, we have shown that total burnout scores and emotional exhaustion (EE) scores were significantly higher in psychiatrists with SCT. SCT scores were positively correlated with mean total burnout, EE, and depersonalization scores. We did not find any differences between subgroups according to departments, therapeutic approaches and gender. In conclusion, we want to highlight that psychiatrists with SCT were more proneness to general burnout symptoms and were more emotionally exhausted regardless of their therapeutic approach or their profession as adult or child/adolescent psychiatrists. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  4. Notch activation inhibits AML growth and survival: a potential therapeutic approach

    Science.gov (United States)

    Kannan, Sankaranarayanan; Sutphin, Robert M.; Hall, Mandy G.; Golfman, Leonard S.; Fang, Wendy; Nolo, Riitta M.; Akers, Lauren J.; Hammitt, Richard A.; McMurray, John S.; Kornblau, Steven M.; Melnick, Ari M.; Figueroa, Maria E.

    2013-01-01

    Although aberrant Notch activation contributes to leukemogenesis in T cells, its role in acute myelogenous leukemia (AML) remains unclear. Here, we report that human AML samples have robust expression of Notch receptors; however, Notch receptor activation and expression of downstream Notch targets are remarkably low, suggesting that Notch is present but not constitutively activated in human AML. The functional role of these Notch receptors in AML is not known. Induced activation through any of the Notch receptors (Notch1–4), or through the Notch target Hairy/Enhancer of Split 1 (HES1), consistently leads to AML growth arrest and caspase-dependent apoptosis, which are associated with B cell lymphoma 2 (BCL2) loss and enhanced p53/p21 expression. These effects were dependent on the HES1 repressor domain and were rescued through reexpression of BCL2. Importantly, activated Notch1, Notch2, and HES1 all led to inhibited AML growth in vivo, and Notch inhibition via dnMAML enhanced proliferation in vivo, thus revealing the physiological inhibition of AML growth in vivo in response to Notch signaling. As a novel therapeutic approach, we used a Notch agonist peptide that led to significant apoptosis in AML patient samples. In conclusion, we report consistent Notch-mediated growth arrest and apoptosis in human AML, and propose the development of Notch agonists as a potential therapeutic approach in AML. PMID:23359069

  5. Viable approach to manage superficial enamel discoloration

    Science.gov (United States)

    Chhabra, Naveen; Singbal, Kiran P.

    2010-01-01

    Esthetics is a primary concern amongst young patients and represents a challenge to the dentist. Discolored teeth are frequently seen in the general population. Several techniques have been devised to minimize or completely eliminate tooth discoloration. This case report highlights the successful management of enamel discoloration via modified microabrasion technique followed by in office bleaching. PMID:22114441

  6. Viable approach to manage superficial enamel discoloration

    Directory of Open Access Journals (Sweden)

    Naveen Chhabra

    2010-01-01

    Full Text Available Esthetics is a primary concern amongst young patients and represents a challenge to the dentist. Discolored teeth are frequently seen in the general population. Several techniques have been devised to minimize or completely eliminate tooth discoloration. This case report highlights the successful management of enamel discoloration via modified microabrasion technique followed by in office bleaching.

  7. 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.

  8. 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.

  9. [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.

  10. Diagnostic and therapeutic approaches in respiratory allergy are different depending on the profile of aeroallergen sensitisation.

    Science.gov (United States)

    Domínguez-Ortega, J; Quirce, S; Delgado, J; Dávila, I; Martí-Guadaño, E; Valero, A

    2014-01-01

    There are few studies which analyse the characteristics of allergic respiratory disease according to profiles of sensitisation to different allergens. This study describes the clinical features and therapeutic approaches, according to the sensitisation profile to relevant aeroallergens, in a sample of adult patients with a first-time diagnosis of respiratory allergy (rhinitis and/or asthma). 1287 patients, enrolled consecutively in the spring of 2010 by 200 allergy specialists, were classified into four groups according to sensitisation to significant allergens in each geographical area (grass pollen, olive pollen, grass and olive pollen, house dust mites). Information was obtained on demographics, diagnostic procedures used, treatments prescribed, clinical characteristics of the rhinitis, and severity and control of asthma. Of the patients, 58.6% had rhinitis only and 38.7% had both rhinitis and asthma. Patients with more severe rhinitis had more severe and poorer controlled asthma. Sensitisation to different allergens was not associated with significant differences in severity and control of asthma, but patients with house dust mite allergy presented persistent rhinitis more frequently. Allergy to grass pollen was significantly associated with food allergies. Differences were observed in the frequency of prescription of immunotherapy and antileukotrienes in patients allergic to house dust mites and of topical corticosteroids in patients with pollen allergy. It was observed in this study that in respiratory allergy disease, there are clinical differences as well as differences in diagnostic procedure and therapeutic attitudes, depending on the clinically relevant allergen. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  11. 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.

  12. Molecular Mechanisms and Novel Therapeutic Approaches to Rhabdomyolysis-Induced Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Nayara Panizo

    2015-10-01

    Full Text Available Rhabdomyolysis is a syndrome caused by injury to skeletal muscle that usually leads to acute kidney injury (AKI. Rhabdomyolysis has been linked to different conditions, including severe trauma and intense physical exercise. Myoglobin-induced renal toxicity plays a key role in rhabdomyolysis-associated kidney damage by increasing oxidative stress, inflammation, endothelial dysfunction, vasoconstriction, and apoptosis. New drugs that target the harmful effects of myoglobin have been recently developed, and some have been proven to be successful in animal models of acute renal failure secondary to rhabdomyolysis. This review aims to provide a comprehensive and updated overview of the pathological mechanisms of renal damage and describes new therapeutic approaches to this condition based on novel compounds that target key pathways involved in myoglobin-mediated kidney damage.

  13. Cytokines during periodontal wound healing: potential application for new therapeutic approach.

    Science.gov (United States)

    Morand, D N; Davideau, J-L; Clauss, F; Jessel, N; Tenenbaum, H; Huck, O

    2017-04-01

    Regeneration of periodontal tissues is one of the main goals of periodontal therapy. However, current treatment, including surgical approach, use of membrane to allow maturation of all periodontal tissues, or use of enamel matrix derivatives, presents limitations in their indications and outcomes leading to the development of new tissue engineering strategies. Several cytokines are considered as key molecules during periodontal destruction process. However, their role during each phase of periodontal wound healing remains unclear. Control and modulation of the inflammatory response and especially, release of cytokines or activation/inhibition in a time- and spatial-controlled manner may be a potential perspective for periodontal tissue engineering. The aim of this review was to summarize the specific role of several cytokines during periodontal wound healing and the potential therapeutic interest of inflammatory modulation for periodontal regeneration especially related to the expression sequence of cytokines. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. [Immunoclinical, molecular and immunopathologic approach to chronic viral hepatitis. Therapeutic considerations].

    Science.gov (United States)

    Machado, I V; Deibis, L; Risquez, E; Tassinari, P; Zabaleta, M E; Toro, F I; Baroja, M L; Corado, J; Ruiz, M E; Longart, L

    1994-01-01

    Through a pilot study which includes a clinical, molecular and immunopathological approach to the chronic Hepatitis induced by HBV or by HCV, we determined that 66% of HBsAg carriers are in the "non viremic" phase. The positive HBeAg "viremic" carriers showed HBV-DNA quantitation which varies between > 50 pg to > 100 pg. Both types of carries are infected with the "wild" type HBV. Each subgroup of positive surface antigemia carriers demonstrated a differential immunopathological response. So far, 96% of the HCV carriers investigated, showed HCV-RNA associated to repeatedly positive anti-HCV antibodies. Those patients with increased ALT values uniformly expressed liver histopathological signs of inflammation caused by HCV; demonstrating also the presence of peripheral blood mononuclear cells infected with HCV. At the present, the genotypes investigation indicates a predominance of HCV genotype II (1b). Autoimmune phenomenons associated to HCV have been detected only in 3 patients. The therapeutic approach with interferon alpha applied to the HCV infection preliminary showed similar results to those reported worldwide. Currently, a comprehensive approach to the chronic HBV and chronic HCV infections requires the application of Immunochemistry, Molecular Biology and Cellular Immunology combined technologies.

  15. 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

  16. A retrosynthetic biology approach to metabolic pathway design for therapeutic production.

    Science.gov (United States)

    Carbonell, Pablo; Planson, Anne-Gaëlle; Fichera, Davide; Faulon, Jean-Loup

    2011-08-05

    Synthetic biology is used to develop cell factories for production of chemicals by constructively importing heterologous pathways into industrial microorganisms. In this work we present a retrosynthetic approach to the production of therapeutics with the goal of developing an in situ drug delivery device in host cells. Retrosynthesis, a concept originally proposed for synthetic chemistry, iteratively applies reversed chemical transformations (reversed enzyme-catalyzed reactions in the metabolic space) starting from a target product to reach precursors that are endogenous to the chassis. So far, a wider adoption of retrosynthesis into the manufacturing pipeline has been hindered by the complexity of enumerating all feasible biosynthetic pathways for a given compound. In our method, we efficiently address the complexity problem by coding substrates, products and reactions into molecular signatures. Metabolic maps are represented using hypergraphs and the complexity is controlled by varying the specificity of the molecular signature. Furthermore, our method enables candidate pathways to be ranked to determine which ones are best to engineer. The proposed ranking function can integrate data from different sources such as host compatibility for inserted genes, the estimation of steady-state fluxes from the genome-wide reconstruction of the organism's metabolism, or the estimation of metabolite toxicity from experimental assays. We use several machine-learning tools in order to estimate enzyme activity and reaction efficiency at each step of the identified pathways. Examples of production in bacteria and yeast for two antibiotics and for one antitumor agent, as well as for several essential metabolites are outlined. We present here a unified framework that integrates diverse techniques involved in the design of heterologous biosynthetic pathways through a retrosynthetic approach in the reaction signature space. Our engineering methodology enables the flexible design of

  17. A retrosynthetic biology approach to metabolic pathway design for therapeutic production

    Directory of Open Access Journals (Sweden)

    Faulon Jean-Loup

    2011-08-01

    Full Text Available Abstract Background Synthetic biology is used to develop cell factories for production of chemicals by constructively importing heterologous pathways into industrial microorganisms. In this work we present a retrosynthetic approach to the production of therapeutics with the goal of developing an in situ drug delivery device in host cells. Retrosynthesis, a concept originally proposed for synthetic chemistry, iteratively applies reversed chemical transformations (reversed enzyme-catalyzed reactions in the metabolic space starting from a target product to reach precursors that are endogenous to the chassis. So far, a wider adoption of retrosynthesis into the manufacturing pipeline has been hindered by the complexity of enumerating all feasible biosynthetic pathways for a given compound. Results In our method, we efficiently address the complexity problem by coding substrates, products and reactions into molecular signatures. Metabolic maps are represented using hypergraphs and the complexity is controlled by varying the specificity of the molecular signature. Furthermore, our method enables candidate pathways to be ranked to determine which ones are best to engineer. The proposed ranking function can integrate data from different sources such as host compatibility for inserted genes, the estimation of steady-state fluxes from the genome-wide reconstruction of the organism's metabolism, or the estimation of metabolite toxicity from experimental assays. We use several machine-learning tools in order to estimate enzyme activity and reaction efficiency at each step of the identified pathways. Examples of production in bacteria and yeast for two antibiotics and for one antitumor agent, as well as for several essential metabolites are outlined. Conclusions We present here a unified framework that integrates diverse techniques involved in the design of heterologous biosynthetic pathways through a retrosynthetic approach in the reaction signature space

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

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    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.

  19. 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.

  20. Tick-borne viruses: a review from the perspective of therapeutic approaches.

    Science.gov (United States)

    Lani, Rafidah; Moghaddam, Ehsan; Haghani, Amin; Chang, Li-Yen; AbuBakar, Sazaly; Zandi, Keivan

    2014-09-01

    Several important human diseases worldwide are caused by tick-borne viruses. These diseases have become important public health concerns in recent years. The tick-borne viruses that cause diseases in humans mainly belong to 3 families: Bunyaviridae, Flaviviridae, and Reoviridae. In this review, we focus on therapeutic approaches for several of the more important tick-borne viruses from these 3 families. These viruses are Crimean-Congo hemorrhagic fever virus (CCHF) and the newly discovered tick-borne phleboviruses, known as thrombocytopenia syndromevirus (SFTSV), Heartland virus and Bhanja virus from the family Bunyaviridae, tick-borne encephalitis virus (TBEV), Powassan virus (POWV), Louping-ill virus (LIV), Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV), and Alkhurma hemorrhagic fever virus (AHFV) from the Flaviviridae family. To date, there is no effective antiviral drug available against most of these tick-borne viruses. Although there is common usage of antiviral drugs such as ribavirin for CCHF treatment in some countries, there are concerns that ribavirin may not be as effective as once thought against CCHF. Herein, we discuss also the availability of vaccines for the control of these viral infections. The lack of treatment and prevention approaches for these viruses is highlighted, and we hope that this review may increase public health awareness with regard to the threat posed by this group of viruses. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

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    Joo Han Lee

    2017-01-01

    Full Text Available 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.

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

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    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.

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

    Science.gov (United States)

    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. CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10.

    Science.gov (United States)

    Ruan, Guo-Xiang; Barry, Elizabeth; Yu, Dan; Lukason, Michael; Cheng, Seng H; Scaria, Abraham

    2017-02-01

    As the most common subtype of Leber congenital amaurosis (LCA), LCA10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. The most frequent mutation found in patients with LCA10 is a deep intronic mutation in CEP290 that generates a cryptic splice donor site. The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy. Here, we show that targeted genomic deletion using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system represents a promising therapeutic approach for the treatment of patients with LCA10 bearing the CEP290 splice mutation. We generated a cellular model of LCA10 by introducing the CEP290 splice mutation into 293FT cells and we showed that guide RNA pairs coupled with SpCas9 were highly efficient at removing the intronic splice mutation and restoring the expression of wild-type CEP290. In addition, we demonstrated that a dual AAV system could effectively delete an intronic fragment of the Cep290 gene in the mouse retina. To minimize the immune response to prolonged expression of SpCas9, we developed a self-limiting CRISPR/Cas9 system that minimizes the duration of SpCas9 expression. These results support further studies to determine the therapeutic potential of CRISPR/Cas9-based strategies for the treatment of patients with LCA10. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  5. 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 [3H]-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 99mTc-NTP 15-5 scintigraphic imaging of PGs, 1H-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.

  6. Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery.

    Science.gov (United States)

    Imbrici, Paola; Liantonio, Antonella; Camerino, Giulia M; De Bellis, Michela; Camerino, Claudia; Mele, Antonietta; Giustino, Arcangela; Pierno, Sabata; De Luca, Annamaria; Tricarico, Domenico; Desaphy, Jean-Francois; Conte, Diana

    2016-01-01

    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.

  7. 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 (TGFβ1) was induced by interleukin-6 (IL6) in human corneal fibroblasts and expression levels of TGFβ1, 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 TGFβ1 and PDGF comparable to that of TGFβ1 knockdown experiment. However, down-regulation of TGFβ1 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.

  8. Enumeration of viable and non-viable larvated Ascaris eggs with quantitative PCR.

    Science.gov (United States)

    Raynal, Maria; Villegas, Eric N; Nelson, Kara L

    2012-12-01

    The goal of this study was to further develop an incubation-quantitative polymerase chain reaction (qPCR) method for quantifying viable Ascaris eggs by characterizing the detection limit and number of template copies per egg, determining the specificity of the method, and testing the method with viable and inactivated larvated eggs. The number of template copies per cell was determined by amplifying DNA from known numbers of eggs at different development stages; the value was estimated to be 32 copies. The specificity of the method was tested against a panel of bacteria, fungi, protozoa and helminths, and no amplification was found with non-target DNA. Finally, fully larvated eggs were inactivated by four different treatments: 254 nm ultraviolet light, 2,000 ppm NH(3)-N at pH 9, moderate heat (48 °C) and high heat (70 °C). Concentrations of treated eggs were measured by direct microscopy and incubation-qPCR. The qPCR signal decreased following all four treatments, and was in general agreement with the decrease in viable eggs determined by microscopy. The incubation-qPCR method for enumerating viable Ascaris eggs is a promising approach that can produce results faster than direct microscopy, and may have benefits for applications such as assessing biosolids.

  9. Genetic rodent models of brain disorders: Perspectives on experimental approaches and therapeutic strategies.

    Science.gov (United States)

    McGraw, Christopher M; Ward, Christopher S; Samaco, Rodney C

    2017-09-01

    Neurobehavioral disorders comprised of neurodegenerative, neurodevelopmental, and psychiatric disorders together represent leading causes of morbidity and mortality. Despite significant academic research and industry efforts to elucidate the disease mechanisms operative in these disorders and to develop mechanism-based therapies, our understanding remains incomplete and our access to tractable therapeutic interventions severely limited. The magnitude of these short-comings can be measured by the growing list of disappointing clinical trials based on initially promising compounds identified in genetic animal models. This review and commentary will explore why this may be so, focusing on the central role that genetic models of neurobehavioral disorders have come to occupy in current efforts to identify disease mechanisms and therapies. In particular, we will highlight the unique pitfalls and challenges that have hampered success in these models as compared to genetic models of non-neurological diseases as well as to symptom-based models of the early 20th century that led to the discovery of all major classes of psychoactive pharmaceutical compounds still used today. Using examples from specific genetic rodent models of human neurobehavioral disorders, we will highlight issues of reproducibility, construct validity, and translational relevance in the hopes that these examples will be instructive toward greater success in future endeavors. Lastly, we will champion a two-pronged approach toward identifying novel therapies for neurobehavioral disorders that makes greater use of the historically more successful symptom-based approaches in addition to more mechanism-based approaches. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

  10. Advances in peripheral nervous system regenerative therapeutic strategies: A biomaterials approach.

    Science.gov (United States)

    Dalamagkas, Kyriakos; Tsintou, Magdalini; Seifalian, Alexander

    2016-08-01

    Peripheral nerve injury is a very common medical condition with varying clinical severity but always great impact on the patients' productivity and the quality of life. Even the current 1st-choice surgical therapeutic approach or the "gold standard" as frequently called in clinical practice, is not addressing the problem efficiently and cost-effectively, increasing the mortality through the need of a second surgical intervention, while it does not take into account the several different types of nerves involved in peripheral nerve injuries. Neural tissue engineering approaches could potentially offer a very promising and attractive tool for the efficient peripheral nerve injury management, not only by mechanically building the gap, but also by inducing neuroregenerative mechanisms in a well-regulated microenvironment which would mimic the natural environment of the specific nerve type involved in the injury to obtain an optimum clinical outcome. There is still room for a lot of optimizations in regard to the conduits which have been developed with the help of neural engineering since many parameters affect the clinical outcome and the underlying mechanisms are still not well understood. Especially the intraluminal cues controlling the microenvironment of the conduits are in an infantile stage but there is profound potential in the application of the scaffolds. The aim of our review is to provide a quick reference to the recent advances in the field, focusing on the parameters that can significantly affect the clinical potentials of each approach, with suggestions for future improvements that could take the current work from bench to bedside. Thus, further research could shed light to those questions and it might hold the key to discover new more efficient and cost-effective therapies. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  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.

    2015-01-01

    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. PMID:26973429

  13. 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.

  14. Novel therapeutic approaches: Rett syndrome and human induced pluripotent stem cell technology

    Science.gov (United States)

    Gomathi, Mohan

    2017-01-01

    Recent advances in induced pluripotent stem cell (iPSC) technology target screening and discovering of therapeutic agents for the possible cure of human diseases. Human induced pluripotent stem cells (hiPSC) are the right kind of platform for testing potency of specific active compounds. Ayurveda, the Indian traditional system of medicine developed between 2,500 and 500 BC, is a science involving the intelligent formulations of herbs and minerals. It can serve as a “goldmine” for novel neuroprotective agents used for centuries to treat neurological disorders. This review discusses limitations in screening drugs for neurological disorders and the advantages offered by hiPSC integrated with Indian traditional system of medicine. We begin by describing the current state of hiPSC technology in research on Rett syndrome (RTT) followed by the current controversies in RTT research combined with the emergence of patient-specific hiPSC that indicate an urgent need for researchers to understand the etiology and drug mechanism. We conclude by offering recommendations to reinforce the screening of active compounds present in the ayurvedic medicines using the human induced pluripotent neural model system for research involving drug discovery for RTT. This integrative approach will fill the current knowledge gap in the traditional medicines and drug discovery. PMID:28447035

  15. 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.

  16. 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.

  17. Transferrin trojan horses as a rational approach for the biological delivery of therapeutic peptide domains.

    Science.gov (United States)

    Ali, S A; Joao, H C; Hammerschmid, F; Eder, J; Steinkasserer, A

    1999-08-20

    One novel approach for the biological delivery of peptide drugs is to incorporate the sequence of the peptide into the structure of a natural transport protein, such as human serum transferrin. To examine whether this is feasible, a peptide sequence cleavable by the human immunodeficiency virus type 1 protease (VSQNYPIVL) was inserted into various regions of human serum transferrin, and the resultant proteins were tested for function. Experimentally, molecular modeling was used to identify five candidate insertion sites in surface exposed loops of human serum transferrin that were distant from biologically active domains. These insertions were cloned using polymerase chain reaction mutagenesis, and the proteins were expressed using a baculovirus expression vector system. Analysis of the mutant proteins provided a number of important findings: (a) they retained native human serum transferrin function, (b) the inserted peptide sequence was surface exposed, and most importantly, (c) two of these mutants could be cleaved by human immunodeficiency virus-1 protease. In conclusion, this investigation has validated the use of human serum transferrin as a carrier protein for functional peptide domains introduced into its structure using protein engineering. These findings will be useful for developing a novel class of therapeutic agents for a broad spectrum of diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art

    Directory of Open Access Journals (Sweden)

    Miroslav Radenković

    2013-01-01

    Full Text Available The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells’ count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

  20. 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

  1. Inhibition of Pim1 kinase, new therapeutic approach in virus-induced asthma exacerbations

    NARCIS (Netherlands)

    Vries, de Maaike; Bedke, Nicole; Smithers, Natalie P.; Loxham, Matthew; Howarth, Peter H.; Nawijn, Martijn C.; Davies, Donna E.

    Therapeutic options to treat virus-induced asthma exacerbations are limited and urgently needed. Therefore, we tested Pim1 kinase as potential therapeutic target in human rhinovirus (HRV) infections. We hypothesised that inhibition of Pim1 kinase reduces HRV replication by augmenting the

  2. Emetophobia (specific phobia of vomiting: It’s Relationship with Anxiety-related Disorders and Cognitive Behavioral Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Vahdet Gormez

    2017-04-01

    Full Text Available Emetophobia (specific phobia of vomiting emerges as one of the most neglected clinical conditions in clinical practice and academic literature. In this article, a phenomenological, epidemiologic and clinical picture of emetophobia is presented and the cognitive behavioral model is discussed as a therapeutic approach for its treatment [JCBPR 2017; 6(1.000: 39-48

  3. Dual Inhibition of Bruton's Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat Non-Hodgkin's B Cell Malignancies.

    Science.gov (United States)

    Alfaro, Jennifer; Pérez de Arce, Felipe; Belmar, Sebastián; Fuentealba, Glenda; Avila, Patricio; Ureta, Gonzalo; Flores, Camila; Acuña, Claudia; Delgado, Luz; Gaete, Diana; Pujala, Brahmam; Barde, Anup; Nayak, Anjan K; Upendra, T V R; Patel, Dhananjay; Chauhan, Shailender; Sharma, Vijay K; Kanno, Stacy; Almirez, Ramona G; Hung, David T; Chakravarty, Sarvajit; Rai, Roopa; Bernales, Sebastián; Quinn, Kevin P; Pham, Son M; McCullagh, Emma

    2017-05-01

    Although new targeted therapies, such as ibrutinib and idelalisib, have made a large impact on non-Hodgkin's lymphoma (NHL) patients, the disease is often fatal because patients are initially resistant to these targeted therapies, or because they eventually develop resistance. New drugs and treatments are necessary for these patients. One attractive approach is to inhibit multiple parallel pathways that drive the growth of these hematologic tumors, possibly prolonging the duration of the response and reducing resistance. Early clinical trials have tested this approach by dosing two drugs in combination in NHL patients. We discovered a single molecule, MDVN1003 (1-(5-amino-2,3-dihydro-1H-inden-2-yl)-3-(8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine), that inhibits Bruton's tyrosine kinase and phosphatidylinositol-3-kinase δ, two proteins regulated by the B cell receptor that drive the growth of many NHLs. In this report, we show that this dual inhibitor prevents the activation of B cells and inhibits the phosphorylation of protein kinase B and extracellular signal-regulated kinase 1/2, two downstream mediators that are important for this process. Additionally, MDVN1003 induces cell death in a B cell lymphoma cell line but not in an irrelevant erythroblast cell line. Importantly, we found that this orally bioavailable dual inhibitor reduced tumor growth in a B cell lymphoma xenograft model more effectively than either ibrutinib or idelalisib. Taken together, these results suggest that dual inhibition of these two key pathways by a single molecule could be a viable approach for treatment of NHL patients. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Enzymatic isolation of viable human odontoblasts.

    Science.gov (United States)

    Cuffaro, H M; Pääkkönen, V; Tjäderhane, L

    2016-05-01

    To improve an enzymatic method previously used for isolation of rat odontoblasts to isolate viable mature human odontoblasts. Collagenase I, collagenase I/hyaluronidase mixture and hyaluronidase were used to extract mature human odontoblasts from the pulp chamber. Detachment of odontoblasts from dentine was determined with field emission scanning electron microscopy (FESEM) and to analyse the significance of differences in tubular diameter, and the t-test was used. MTT-reaction was used to analyse cell viability, and nonparametric Kruskal-Wallis and Mann-Whitney post hoc tests were used to analyse the data. Immunofluorescent staining of dentine sialoprotein (DSP), aquaporin-4 (AQP4) and matrix metalloproteinase-20 (MMP-20) and quantitative PCR (qPCR) of dentine sialophosphoprotein (DSPP) were used to confirm the odontoblastic nature of the cells. MTT-reaction and FESEM demonstrated collagenase I/hyaluronidase resulted in more effective detachment and higher viability than collagenase I alone. Hyaluronidase alone was not able to detach odontoblasts. Immunofluorescence revealed the typical odontoblastic-morphology with one process, and DSP, AQP4 and MMP-20 were detected. Quantitative PCR of DSPP confirmed that the isolated cells expressed this odontoblast-specific gene. The isolation of viable human odontoblasts was successful. The cells demonstrated morphology typical for odontoblasts and expressed characteristic odontoblast-type genes and proteins. This method will enable new approaches, such as apoptosis analysis, for studies using fully differentiated odontoblasts. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  5. Sclerostin inhibition: a novel therapeutic approach in the treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Shah AD

    2015-06-01

    Full Text Available Arti D Shah,1 Dolores Shoback,1,2 E Michael Lewiecki3,4 1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; 2Endocrine Research Unit, Department of Medicine, Veterans Affairs Medical Center, San Francisco, CA, USA; 3University of New Mexico School of Medicine, Albuquerque, NM, USA; 4New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA Abstract: Osteoporosis and osteoporosis-related fractures are growing problems with the aging population and are associated with significant morbidity and mortality. At this time, other than parathyroid hormone analogs, all therapies for osteoporosis are antiresorptive. Therefore, researchers have focused efforts on development of more anabolic therapies. Understanding of the Wnt signaling pathway, which is critical for skeletal development, and the role of sclerostin in inhibition of Wnt signaling has led to the discovery of a novel therapeutic approach in the treatment of osteoporosis – sclerostin inhibition. In this review, we discuss the biology of Wnt signaling and sclerostin inhibition. We then discuss human disorders of decreased sclerostin function and animal models of sclerostin inhibition. Both have served to elucidate the effects of decreased sclerostin levels and function – increased bone mass and strength and fewer fractures. In addition, we review data from Phase I and II studies of the two humanized sclerostin monoclonal antibodies, romosozumab and blosozumab, both of which have had positive effects on bone mineral density. We conclude with a discussion of the ongoing Phase III studies of romosozumab. The available data support the potential for neutralizing sclerostin monoclonal antibodies to serve as anabolic agents in the treatment of osteoporosis. Keywords: osteoporosis, sclerostin, Wnt signaling, anabolic therapies, romosozumab 

  6. A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient

    Directory of Open Access Journals (Sweden)

    Wallace John L

    2008-01-01

    Full Text Available Abstract Background We examined the therapeutic potential of a proprietary Croton palanostigma extract (Zangrado® in the management of emesis and itch. Methods Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc in the presence of Zangrado (3 mg/kg, ip and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip. Topical Zangrado (1% was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the ApcMinmouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production. Results Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the ApcMincondition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages. Conclusion Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.

  7. Positron emission tomography for staging esophageal cancer: does it lead to a different therapeutic approach?

    Science.gov (United States)

    Kneist, Werner; Schreckenberger, Mathias; Bartenstein, Peter; Grünwald, Frank; Oberholzer, Katja; Junginger, Theodor

    2003-10-01

    Accurate preoperative staging is essential for the indication and selection of the appropriate surgical procedure in patients with esophageal cancer. The present prospective study was designed to determine if the preoperative use of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) increases the accuracy of staging esophageal cancer compared with computed tomography (CT) and if it thereby leads to a different therapeutic approach. A total of 58 patients, 46 men and 12 women (mean age 61 years), with histologic proof of esophageal carcinoma underwent FDG-PET of the neck, chest, and abdomen, as well as CT of the chest and abdomen, to determine tumor stage. FDG-PET and CT data were compared with each other and with pathohistologic findings. Sensitivity, specificity, and overall accuracy for detecting histologically verified lymph node and distant metastases were calculated for FDG-PET and CT. FDG-PET showed a higher specificity, whereas CT had higher accuracy for detecting both abdominal (73% vs. 59%) and thoracic (73% vs. 63%) lymph node metastases. The accuracy of detecting blood-borne and lymphatic distant metastases was identical for CT and FDG-PET imaging (50%). FDG-PET had a higher specificity than CT (87% vs. 13%) but lower sensitivity (35% vs. 67%). FDG-PET did not provide new information on the indication for surgery, nor was it helpful for choosing the appropriate surgical procedure in patients with esophageal carcinoma. In view of the relatively high cost of FDG-PET examinations, the use of this modality is indicated primarily in patients with inconclusive CT findings or for scientific research projects. Higher sensitivity as a result of tumor-affinity radiopharmaceuticals and optimized apparatus resolution, in addition to the advantages offered by whole-body PET scanning, may lead to new indications for this staging procedure in the future.

  8. Targeting the Notch pathway: A potential therapeutic approach for desmoid tumors.

    Science.gov (United States)

    Shang, Hui; Braggio, Danielle; Lee, Ya-Jung; Al Sannaa, Ghadah A; Creighton, Chad J; Bolshakov, Svetlana; Lazar, Alexander J F; Lev, Dina; Pollock, Raphael E

    2015-11-15

    Desmoid tumors (DTs) are rare mesenchymal lesions that can recur repeatedly. When it is feasible, DTs are surgically resected; however, this often results in high recurrence rates. Recently, treatment with PF-03084014, a potent γ-secretase inhibitor, has been shown to have antitumor activity in several tumor types by affecting the WNT/β-catenin pathway. Consequently, Notch pathway inhibition by PF-03084014 might be a promising approach for DT treatment. The expression of Notch pathway components was analyzed in DT tissues and cell strains with immunohistochemistry and Western blotting, respectively. A panel of DT cell strains was exposed to PF-03084014 and evaluated for cell proliferation. Antitumor effects were assessed via cell cycle, apoptosis, and migration and invasion analysis. Cells treated with PF-03084014 were characterized with a gene array analysis combined with Ingenuity Pathway Analysis. The results showed that Notch pathway components were expressed at different levels in DTs. Hes1 (Hes Family BHLH Transcription Factor 1) was overexpressed in DT tumors versus dermal scar tissue, and PF-03084014 caused significant decreases in Notch intracellular domain and Hes1 expression in DT cell strains. PF-03084014 decreased DT cell migration and invasion and also caused cell growth inhibition in DT cell strains, most likely through cell cycle arrest. Gene array analysis combined with Ingenuity Pathway Analysis showed that Wnt1-inducible signaling pathway protein 2 possibly regulated Notch and WNT pathways after treatment with PF-03084014 through integrin. Our findings suggest that the Notch pathway is an important DT therapeutic target. Furthermore, PF-03084014 has significant antitumor activity against DTs, and it may be an alternative strategy for DT treatment. © 2015 American Cancer Society.

  9. Analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in Spain.

    Science.gov (United States)

    Ibáñez, María Dolores; Valero, Antonio Luis; Montoro, Javier; Jauregui, Ignacio; Ferrer, Marta; Dávila, Ignacio; Bartra, Joan; Del Cuvillo, Alfonso; Mullol, Joaquim; Sastre, Joaquín

    2013-11-01

    Allergic rhinitis (AR) is the most common chronic disease in children. The main objective of this study was to analyze the comorbidities and therapeutic approaches for AR in a Spanish pediatric population. Children aged 6 to 12 years with AR were included in an observational, cross-sectional, multicenter study. 1,275 children were recruited from 271 centers. AR was intermittent in 59.5% of cases, persistent in 40.5%, seasonal in 60.7%, and perennial in 39.3% of patients. The most frequent comorbidities were conjunctivitis (53.6%), asthma (49.5%), atopic dermatitis (40%), rhinosinusitis(26.1%), otitis media (23.8%), and adenoid hypertrophy (17.3%). Overall, patients with persistent, moderate or severe, AR were more likely to present comobidities, except for food allergy and urticaria. The most common drugs used for treatment of AR were oral antihistamines(76%), nasal corticosteroids(49%) and a combination of both (45%). Antihistamines and nasal corticosteroids were used on demand (<18 days) in 38 and 41% of patients, respectively; for 18-30 days in 22 and 27%; for 1-3 months in 31 and 29%; and for more than 3 months in 8 and 3%, respectively. Eye drops were used in 32% and specific immunotherapy in 21% of patients. Comorbidities are frequent in children with AR, supporting the notion of allergy as a systemic disease. Severity and duration of AR were significantly associated with presence of most of comorbidities. The most common drugs used for AR treatment were oral antihistamines, followed by nasal corticosteroids and a combination of both used on demand. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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.

  11. The therapeutic effect of percutaneous transforaminal endoscopic discectomy through interlaminar approach for treating lumbar disc herniation

    Directory of Open Access Journals (Sweden)

    Wan-ru DUAN

    2016-04-01

    Full Text Available Objective To evaluate the therapeutic efficacy of percutaneous transforaminal endoscopic discectomy (PTED through interlaminar approach in the treatment of lumbar disc herniation (LDH.  Methods From October 2013 to January 2015, 54 LDH patients underwent PTED by using transforaminal endoscopic spine system (TESSYS in our hospitial. CT or MRI indicated L4-5 disc herniation in 13 patients and L5-S1 disc herniation in other 41 patients. Visual Analogue Scale (VAS and Oswestry Disability Index (ODI were used to evaluate the degree of pain in the low back and leg before operation, one day, 3 months and one year after operation. MRI was performed after operation to assess if the nucleus pulposus was removed completely and whether there was a relapse.  Results The success rate of operations was 96.30% (52/54. Two patients suffered from rupture of spinal dura mater during the surgery, and underwent fenestration laminectomy in turn. The average operation time was 58.35 min and median hospital stay was 3 d. At discharge, pain was disappeared in 52 patients and relieved in 2 patients, however, 5 patients presented worsened numbness of lateral lower leg. Compared with preoperation, VAS and ODI scores decreased significantly one day, 3 months and one year after operation (P = 0.000, for all. Lumbar MRI one day after operation revealed nucleus pulposus had been completely removed and the compression of nerve root had been relieved in all cases. There was no relapse in MRI findings 3 months and one year after operation. No surgical complication, such as infection, was found. One patient with L5-S1 disc herniation presented postoperative numbness of S1 nerve root region caused by heavy stretching of nerve root during the operation, and was improved one month later.  Conclusions Percutaneous transforaminal endoscopic discectomy through interlaminar approach in the treatment of lumbar disc herniation is effective and safe. DOI: 10.3969/j.issn.1672-6731.2016.04.006

  12. Finasteride adverse effects in subjects with androgenic alopecia: A possible therapeutic approach according to the lateralization process of the brain.

    Science.gov (United States)

    Motofei, Ion G; Rowland, David L; Georgescu, Simona R; Tampa, Mircea; Baconi, Daniela; Stefanescu, Emil; Baleanu, Bogdan C; Balalau, Cristian; Constantin, Vlad; Paunica, Stana

    2016-11-01

    Nowadays, finasteride is a relatively frequently prescribed drug in the therapeutic management of male androgenic alopecia. The reported adverse effects are notable in some patients, consisting in signs and symptoms that are encountered both during finasteride administration and after treatment cessation. Clinical and imagistic data show that cognition and sexuality are two distinct but interrelated environmental functions, most probable due to lateralization process of the brain. Specific for our topic, relatively recent published studies found that frequency and severity of finasteride adverse effects could be interrelated with hand preference and sexual orientation of the respective subjects. This paper tries to explain/support this interrelation through a psychophysiologic approach, to suggest how this premise could be further proved in dermatological practice, and to highlight its relevance in respect to therapeutic approach of male androgenic alopecia. As a possible therapeutic application, subjects having preference for a certain sexual orientation and/or predisposition for a given dominant hand could be advised before finasteride administration, that present an increased risk/sensitivity to develop adverse effects. Finally, even if finasteride and post-finasteride symptoms overlap to a large extent they should be, however, viewed as distinct physiopathologic entities, which could require perhaps different therapeutic approaches.

  13. Therapeutic Improvement of Scarring: Mechanisms of Scarless and Scar-Forming Healing and Approaches to the Discovery of New Treatments

    Directory of Open Access Journals (Sweden)

    Nick L. Occleston

    2010-01-01

    Full Text Available Scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in loss of function, restriction of tissue movement and adverse psychological effects. Whilst various studies have utilised a range of model systems that have increased our understanding of the pathways and processes underlying scar formation, they have typically not translated to the development of effective therapeutic approaches for scar management. Existing treatments are unreliable and unpredictable and there are no prescription drugs for the prevention or treatment of dermal scarring. As a consequence, scar improvement still remains an area of clear medical need. Here we describe the basic science of scar-free and scar-forming healing, the utility of pre-clinical model systems, their translation to humans, and our pioneering approach to the discovery and development of therapeutic approaches for the prophylactic improvement of scarring in man

  14. Viable Syntax: Rethinking Minimalist Architecture

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    Ken Safir

    2010-03-01

    Full Text Available Hauser et al. (2002 suggest that the human language faculty emerged as a genetic innovation in the form of what is called here a ‘keystone factor’—a single, simple, formal mental capability that, interacting with the pre-existing faculties of hominid ancestors, caused a cascade of effects resulting in the language faculty in modern humans. They take Merge to be the keystone factor, but instead it is posited here that Merge is the pre-existing mechanism of thought made viable by a principle that permits relations interpretable at the interfaces to be mapped onto c-command. The simplified minimalist architecture proposed here respects the keystone factor as closely as possible, but is justified on the basis of linguistic analyses it makes available, including a relativized intervention theory applicable across Case, scope, agreement, selection and linearization, a derivation of the A/A’-distinction from Case theory, and predictions such as why in situ wh-interpretation is island-insensitive, but susceptible to intervention effects.

  15. 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

  16. Soteria Berne: an innovative milieu therapeutic approach to acute schizophrenia based on the concept of affect-logic

    Science.gov (United States)

    Ciompi, Luc; Hoffmann, Holger

    2004-01-01

    The name "Soteria" stands for an alternative low-drug milieu-therapeutic approach to acute schizophrenia that was first implemented by Mosher and Menn in San Francisco, and since 1984 further developed by Ciompi and co-workers in Berne, on the basis of their concept of affect-logic, that emphasizes the often neglected influence of emotional factors in schizophrenia. In both settings, equal and even partly better therapeutic results, compared with traditional methods, were obtained with much lower doses of antipsychotics and comparable daily costs. Basic concepts, practical proceedings and empirical findings of Soteria Berne are reported, and their theoretical and practical implications for mainstream psychiatry are discussed. They support the hypothesis of a crucial pathogenetic and therapeutic-preventive role played by emotional factors not only in the so-called affective psychoses, but also in schizophrenia. PMID:16633478

  17. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Anaphylaxis in referred pediatric patients: demographic and clinical features, triggers, and therapeutic approach.

    Science.gov (United States)

    De Swert, Liliane F A; Bullens, Dominique; Raes, Marc; Dermaux, Anna-Maria

    2008-11-01

    Anaphylaxis remains under-diagnosed and under-treated. A better knowledge of patterns and triggers of anaphylaxis might contribute to a better management. In this study we evaluated the demographic and clinical features of anaphylaxis in pediatric patients, as well as its triggers and therapeutic approach. From May 1st 2004 until April 30th 2006 we prospectively collected data on all patients referred for investigation of anaphylaxis to the pediatric department of the University Hospital Gasthuisberg Leuven and to two private pediatric practices. Data were stored in a MYSQL database by use of an online encrypted web form. Sixty-four cases of anaphylaxis occurred in 48 children, aged 6 months to 14.8 years. Twenty-seven episodes (42.2%) occurred at home. The symptoms were dermatologic in 62 (96.9%) episodes, respiratory in 57 (89.1%), gastrointestinal in 19 (29.7%), cardiovascular in 14 (21.8%), and neurological or behavioural in 19 (29.7%). Antihistamines were administered in 41/57 (71.9%) cases, corticosteroids in 26/57 (45.6%), beta-2-mimetics in 14/57 (24.6%), and adrenaline in 11/57 (19.3%). Out of nine cases where Epipen was available at the moment of anaphylaxis, it was administered in one case only. Food was the cause of anaphylaxis in 42/55 (76.4%) cases with identified trigger, while medication, insect stings, latex, and birch pollen triggered 5 (9.1%), 4 (7.3%), 3 (5.5%), and 1 (1.8%) case(s), respectively. Allergy to the trigger was known prior to anaphylaxis in 19/55 (34.5%) cases. In conclusion, anaphylaxis in pediatric patients generally presents with dermatologic and respiratory symptoms, while in 1/5 episodes cardiovascular symptoms occur. Food is by far the most frequent trigger. Allergy to the trigger is known in 1/3 cases only. Anaphylaxis is under-treated, even when appropriate medication is available.

  20. 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.

  1. Novel Therapeutic Approaches for the Treatment of Depression and Cognitive Deficits in a Rodent Model of Gulf War Veterans Illness

    Science.gov (United States)

    2015-10-01

    in this cascade produces depressive symptoms and memory impairments, and inhibiting this system with pharmacological or genetic manipulation affords...1 AWARD NUMBER: W81XWH-14-1-0478 TITLE: Novel Therapeutic Approaches for the Treatment of Depression and Cognitive Deficits in a Rodent Model...the Treatment of Depression and Cognitive Deficits in a Rodent Model of Gulf War Veterans’ Illness 5b. GRANT NUMBER W81XWH-14-1-0478 5c

  2. Knockout of Apolipoprotein E in rabbit promotes premature intervertebral disc degeneration: A new in vivo model for therapeutic approaches of spinal disc disorders

    Science.gov (United States)

    Beierfuß, Anja; Dietrich, Hermann; Kremser, Christian; Hunjadi, Monika; Ritsch, Andreas; Rülicke, Thomas; Thomé, Claudius

    2017-01-01

    Intervertebral disc (IVD) degeneration that accelerates the loss of disc structural and functional integrities is recognized as one of the major factors of chronic back pain. Cardiovascular risk factors, such as deficits of apolipoproteins that elevate the levels of cholesterol and triglycerides, are considered critical for the progress of atherosclerosis; notably in the abdominal aorta and its lumbar branching arteries that supply lumbar vertebrae and IVDs. Obstruction of the lumbar arteries by atherosclerosis is presumed to promote lumbar disc degeneration and low back pain. APOE-knockout rabbits have recently been shown to generate hyperlipidemia with increased levels of cholesterol and triglycerides that mimic the symptoms of atherosclerosis in humans. Here, we analysed IVD degeneration in the lumbar spines of ten homozygous APOE-knockout and four wild-type New Zealand White rabbits of matching age to prove accelerated IVD degeneration in APOE-knockout rabbits, since APOE-knockout rabbits could be a beneficial model for therapeutic approaches of degenerative IVD disorders. Experiments were performed using T1/T2-weighted magnetic resonance imaging, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, glucose-oxidase assay, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot. APOE-knockout lumbar spines showed more advanced IVD degeneration, obstructed lumbar arteries and lower enhancement of contrast agent in IVDs. Moreover, lower concentration of glucose, lower number of viable cells and lower concentrations of aggrecan, collagen II and higher concentration of collagen I were detected in APOE-knockout IVDs (p rabbits could induce structurally deteriorating premature IVD degeneration that mimics the symptoms of accelerated IVD degeneration in humans. APOE-knockout rabbits could be used as beneficial model, as they can bypass the standard surgical interventions that are commonly applied in research animals for

  3. The Role of Group Counseling With Logo-Therapeutic Approach on the Mental Health of Older Women

    Directory of Open Access Journals (Sweden)

    Farshad Fakhar

    2008-04-01

    Full Text Available Objectives: Ageing is the end point of a developmental process which begins with the birth. It is not necessarily accompanied by diseases and disorders, although some are more prevalent in this period. Reportedly mental health problems, especially anxiety and depression, are seen frequently among older people which need more consideration, both in diagnosis and management. Considering the complexities of drug treatment in aging people, using psychotherapeutic approaches has been recommended. This research aimed to investigate the effects of a group counseling program based on logo-therapy concepts on the elderly women residing in the Kahrizak Nursing Home. Methods & Materials: A semi- experimental design was used. Eighteen randomly selected elderly women aged more than 60 years old were evaluated by GHQ-28. Matched according to their GHQ scores, they divided in 2 equal groups. Ten weekly therapeutic group sessions implemented. The subjects were evaluated again by the same instrument. The gathered data analyzed using t test. Results: The results showed that logo-therapeutic approach group therapy led to better mental health of the subjects (P=0.005. This effect was more significant in anxiety (P=0.015 and social (P=0.005 aspects of mental health than depression (P=0.86 and somatic (P=0.13 aspects. Conclusion: Group counseling with logo-therapeutic approach may lead to a better mental health of institutionalized elderly women, hence its application is recommended.

  4. Therapeutic Approaches in Lowering Albuminuria : Travels Along the Renin-Angiotensin-Aldosterone-System Pathway

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.

    Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in these patients. However, despite these

  5. Pulmonology meets rheumatology in sarcoidosis: a review on the therapeutic approach

    NARCIS (Netherlands)

    Drent, M.; Cremers, J.P.; Jansen, T.L.Th.A.

    2014-01-01

    PURPOSE OF REVIEW: Sarcoidosis is a systemic disease characterized by the formation of granulomas in various organs, mainly lungs and lymphatic system. Joint, muscle, and bone involvement is also rather common. Recent studies on its pathogenesis and therapeutic management are reviewed here. RECENT

  6. 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. 

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

    NARCIS (Netherlands)

    Lemos, A.; Melo, Rita; de Sousa Moreira, I.|info:eu-repo/dai/nl/412025000; 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

  8. 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.

  9. 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.

  10. Spinal cord injury induced neuropathic pain: Molecular targets and therapeutic approaches.

    Science.gov (United States)

    Schomberg, Dominic; Miranpuri, Gurwattan; Duellman, Tyler; Crowell, Andrew; Vemuganti, Raghu; Resnick, Daniel

    2015-06-01

    Neuropathic pain, especially that resulting from spinal cord injury, is a tremendous clinical challenge. A myriad of biological changes have been implicated in producing these pain states including cellular interactions, extracellular proteins, ion channel expression, and epigenetic influences. Physiological consequences of these changes are varied and include functional deficits and pain responses. Developing therapies that effectively address the cause of these symptoms require a deeper knowledge of alterations in the molecular pathways. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are two promising therapeutic targets. Matrix metalloproteinases interact with and influence many of the studied pain pathways. Gene expression of ion channels and inflammatory mediators clearly contributes to neuropathic pain. Localized and time dependent targeting of these proteins could alleviate and even prevent neuropathic pain from developing. Current therapeutic options for neuropathic pain are limited primarily to analgesics targeting the opioid pathway. Therapies directed at molecular targets are highly desirable and in early stages of development. These include transplantation of exogenously engineered cell populations and targeted gene manipulation. This review describes specific molecular targets amenable to therapeutic intervention using currently available delivery systems.

  11. [Sociability networks: approaches based on home-based therapeutic care services].

    Science.gov (United States)

    Argiles, Carmen Terezinha Leal; Kantorski, Luciane Prado; Willrich, Janaína Quinzen; Antonacci, Milena Hohmann; Coimbra, Valéria Cristina Christello

    2013-07-01

    Home-based therapeutic services emerge in the context of psychiatric reform in Brazil, as a step forward in the policy of de-institutionalization, as well as being essential services to overcome custody practices, typical of the asylum model. These services provide spaces for care, welcome and decent housing for people whose family and social ties have been affected by internment in psychiatric hospitals. The article seeks to evaluate the sociability network of users of home-based therapeutic services in Alegrete in the State of Rio Grande do Sul, based on a case report. This study is part of the research on 'Networks that Rehabilitate'--evaluating innovative experiments in the composition of psychosocial care networks. Data from semi-structured interviews with the six workers of the service were used. It was observed that the service provides unique and innovative experience to find solutions that bring people with long periods of psychiatric hospitalization back together with their family, the community and city life, thereby eliminating the segregation to which they were subjected. Coaching residents and workers in the creation of home-based therapeutic care services reveals the potential to reintegrate mentally handicapped patients into society.

  12. [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.

  13. Ischemic left ventricle systolic dysfunction: An evidence-based approach in diagnostic tools and therapeutics

    Directory of Open Access Journals (Sweden)

    Eduardo Gomes Lima

    Full Text Available Summary Coronary artery disease (CAD associated with left ventricular systolic dysfunction is a condition related to poor prognosis. There is a lack of robust evidence in many aspects related to this condition, from definition to treatment. Ischemic cardiomyopathy is a spectrum ranging from stunned myocardium associated with myocardial fibrosis to hibernating myocardium and repetitive episodes of ischemia. In clinical practice, relevance lies in identifying the myocardium that has the ability to recover its contractile reserve after revascularization. Methods to evaluate cellular integrity tend to have higher sensitivity, while the ones assessing contractile reserve have greater specificity, since a larger mass of viable myocytes is required in order to generate contractility change. Since there are many methods and different ways to detect viability, sensitivity and specificity vary widely. Dobutamine-cardiac magnetic resonance with late gadolinium enhancement has the best accuracy is this setting, giving important predictors of prognostic and revascularization benefit such as scar burden, contractile reserve and end-systolic volume index. The latter has shown differential benefit with revascularization in some recent trials. Finally, authors discuss interventional procedures in this population, focusing on coronary artery bypass grafting and evolution of evidence from CASS to post-STICH era.

  14. Patients' crying experiences in psychotherapy: Relationship with the patient level of personality organization, clinician approach, and therapeutic alliance.

    Science.gov (United States)

    Zingaretti, Pietro; Genova, Federica; Gazzillo, Francesco; Lingiardi, Vittorio

    2017-06-01

    The present study sought to further understand patients' crying experiences in psychotherapy. We asked 64 clinicians to randomly request one patient in their practice to complete a survey concerning crying in psychotherapy as well as a measure of therapeutic alliance. All clinicians provided information regarding their practice and patient diagnostic information. Fifty-five (85.93%) patients cried at least once, and 18 (28.1%) had cried during their most recent session. Patients' frequency of crying episodes in therapy was negatively related with psychotic level of personality organization, while patients' tendency to feel more negative feelings after crying was positively related to lower levels of personality organization. Patients' feeling more in control after crying was positively related with an interpersonal therapeutic approach, while patients' perception of therapists as more supportive after crying was positively related to a psychodynamic approach. Patients' tendency to experience more negative feelings after crying was significantly related with both lower levels of personality organization and patients' perception of the therapeutic alliance as weak. In regard to their most recent crying event in treatment, therapeutic alliance was related to gaining a new understanding of experience not previously recognized by the patient. Further, patients' experiences of having never told anyone about their experience related to a crying episode, as well as their realization of new ideas and feeling of having communicated something that words could not express was positively related to the goal dimension of alliance. Patients' perception of crying as a moment of genuine vulnerability, greater feelings of self-confidence and self-disclosure as well as having had a therapist response that was compassionate and supportive, was positively related with the bond dimension of alliance. Clinical implications and future research directions regarding patient crying

  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. Bimetric gravity is cosmologically viable

    Directory of Open Access Journals (Sweden)

    Yashar Akrami

    2015-09-01

    Full Text Available Bimetric theory describes gravitational interactions in the presence of an extra spin-2 field. Previous work has suggested that its cosmological solutions are generically plagued by instabilities. We show that by taking the Planck mass for the second metric, Mf, to be small, these instabilities can be pushed back to unobservably early times. In this limit, the theory approaches general relativity with an effective cosmological constant which is, remarkably, determined by the spin-2 interaction scale. This provides a late-time expansion history which is extremely close to ΛCDM, but with a technically-natural value for the cosmological constant. We find Mf should be no larger than the electroweak scale in order for cosmological perturbations to be stable by big-bang nucleosynthesis. We further show that in this limit the helicity-0 mode is no longer strongly-coupled at low energy scales.

  17. Proteolytic clearance of extracellular α-synuclein as a new therapeutic approach against Parkinson disease.

    Science.gov (United States)

    Park, Sang Myun; Kim, Kwang Soo

    2013-01-01

    Many neurodegenerative diseases such as Alzheimer disease and Parkinson disease show similar characteristics. They typically show deposits of protein aggregates, the formation of which is considered important in their pathogenesis. Recently, aggregation-prone proteins have been shown to spread between cells and so may contribute to the pathogenesis of diseases like prion disease. Such a pathogenesis pathway is possibly common to many neurodegenerative diseases. If confirmed, it could allow the development of therapeutic interventions against many such diseases. In Parkinson disease, α-synuclein, a major component of cytosolic protein inclusions named Lewy body, has been shown to be released and taken up by cells, which may facilitate its progressive pathological spreading between cells. Accordingly, inhibition of spreading by targeting extracellular α-synuclein may represent a new therapy against Parkinson disease. Research into the intercellular spreading of extracellular protein aggregations of α-synuclein and its clearance pathway are reviewed here with a focus on the proteolytic clearance pathway as a therapeutic target for the treatment of Parkinson disease. Considering the similar characteristics of aggregation-prone proteins, these clearance systems might allow treatment of other neurodegenerative diseases beyond Parkinson disease.

  18. Recent developments leading toward a paradigm switch in the diagnostic and therapeutic approach to human leishmaniasis.

    Science.gov (United States)

    Schriefer, Albert; Wilson, Mary E; Carvalho, Edgar M

    2008-10-01

    To identify recent papers showing how human and parasite genetics influence leishmaniasis, and how understanding of the immunopathology may be utilized in immunotherapy for these diseases. Progress has been made in recent years showing the complexity within populations of Leishmania spp. and indicating that different strains lead to diverse clinical pictures and responses to treatment. Thus detection of parasite genetic tags for the precise identification of infecting strains, and for predictive diagnosis of clinical and therapeutic fates seems now possible. Host genetic loci involved in disease outcome have been detected, which may also be explored for better case management. These developments in diagnosis will demand expanding the therapeutic arsenal to take their expected effect. This is starting to be fulfilled by immunotherapies successfully employed to treat cases refractory to standard first line drugs, as the result of a more profound comprehension of the immunopathology of the leishmaniases. The knowledge mounting has already helped explain why different patients present different forms of leishmaniasis and respond differently to treatment, and may be on the verge of catalyzing a major change in the already over a century old paradigm of diagnosing and managing these patients.

  19. 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

  20. Superoxide dismutase - a target for gene therapeutic approach to reduce oxidative stress in erectile dysfunction.

    Science.gov (United States)

    Deng, W; Bivalacqua, T J; Champion, H C; Hellstrom, W J; Murthy, Subramanyam N; Kadowitz, Philip J

    2010-01-01

    Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. Oxidative stress has been demonstrated to be involved in the pathophysiology of age- or diabetes-related ED. Superoxide dismutase (SOD), an antioxidant enzyme catalyzing the conversion of superoxide anion (O(2) (-)) to hydrogen peroxide (H(2)O(2)) and molecular oxygen (O(2)), is a promising therapeutic target for ED. In vivo gene therapy and adult stem cell-based ex vivo gene therapy are two attractive current gene therapies for the treatment of ED. In this chapter we describe the use of two potent gene transfer techniques to deliver the therapeutic gene extracellular superoxide dismutase (ecSOD) into the penis of aged or diabetic rats for therapy of ED: adenoviral-mediated intracavernosal ecSOD gene transfer for gene therapy of ED and ecSOD gene-modified marrow stromal cells, also known as mesenchymal stem cells, based stem cell and gene therapy.

  1. Diffuse form of Caroli's disease: therapeutical approach in a female patient with recurrent cholangitis.

    Science.gov (United States)

    Iancu, Cornel; Bodea, Raluca; Muresan, Terezia; Iancu, Dana; Boruah, Prabir; Al Hajjar, Nadim

    2010-12-01

    A 49-year old female was admitted to the 3rd Surgical Clinic Cluj with clinical signs of cholangitis. She had had these symptoms for 30 years and in 2007 she was diagnosed as suffering from a diffuse form of Caroli's disease. On admission, a biological syndrome of cholestasis was noticed, associated with an inflammatory syndrome and hepatocytolysis. The imaging examinations confirmed the presence of bilateral intrahepatic cysts communicating with the biliary tree and intrahepatic lithiasis. Surgery was performed with left lobectomy, cholecystectomy, lavage of the right biliary tree and single loop cholangio-jejunal Roux-en-Y anastomosis. The patient had a favorable postoperative evolution and was discharged on the 7th day. The optimal therapeutic solution for this patient would have been a liver transplantation. However, given the emergency presentation, the surgery choice was to treat the present complications, namely the structural damage in the left lobe, the microabcesses at this level, the intrahepatic lithiasis and cholangitis. Caroli's disease, due to its complications, may impose to the surgeon to choose between different therapeutical strategies before liver transplantation.

  2. Beyond LCDM: a viable alternative?

    CERN Document Server

    Gough, Michael Paul

    2016-01-01

    We are encouraged to look beyond LCDM as there are still no satisfactory explanations for either dark energy or dark matter. A data centred phenomenological approach supports an alternative explanation in which dark energy is not a universe-wide constant energy density, but the Holographic Dark Information Energy, HDIE, naturally centred around galaxies. HDIE can explain many of the effects attributed separately to Lambda and CDM. HDIE mimics Lambda with sufficient overall total energy and an equation of state parameter, w = -1.03+-0.05 for z 1.35, HDIE was phantom, w = -1.82+-0.08, providing a clear prediction that will enable the model to be verified or falsified. HDIE is shown to fit Planck dark energy wo-wa plots at least as well as Lambda, and to be consistent with other results that suggest dark energy was phantom at earlier times. A new w parameterisation is proposed here, as the usual CPL parameterisation is found to be biased and unsuitable for distinguishing between the HDIE/baryon and LCDM models.

  3. Tapping into Salmonella typhimurium LT2 genome in a quest to explore its therapeutic arsenal: A metabolic network modeling approach.

    Science.gov (United States)

    Mehla, Kusum; Ramana, Jayashree

    2017-02-01

    S. typhimurium, the classical broad-host-range serovar is a widely distributed cause of food-borne illness. Escalating antibiotic resistance and potential of conjugal transmission to other pathogens attributable to its broad spectrum host specificities have aided S. typhimurium to emerge as a global health threat. To keep pace with ever evolving bacterial defenses, there is dire need to restock the antibiotic pipeline. Genome scale metabolic reconstructions present immense possibilities to decipher physiological properties of an organism using constraint-based methods The systems-level approaches of genome scale metabolic networks interrogation open up new avenues of drug target identification against deadly infectious diseases. We performed flux balance analysis and minimization of metabolic adjustment studies of genome scale reconstruction model of S. typhimurium targeted at identifying large number of metabolites with a potential to be utilized as therapeutic drug targets. These constraint based approaches initially predict a set of genes indispensable to bacterial survival by performing gene knockout studies which are then prioritized through a multistep process. Metabolites involved in l-rhamnose biosynthesis, peptidoglycan biosynthesis, fatty acid biosynthesis, and folate biosynthesis pathways were prioritized as candidate drug targets. This study provides a general therapeutic approach which can be effectively applied to other pathogens as well. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Therapeutic elements in a self-management approach: experiences from group participation among people suffering from chronic pain

    Directory of Open Access Journals (Sweden)

    Furnes B

    2014-08-01

    Full Text Available Bodil Furnes,1 Gerd Karin Natvig,1,2 Elin Dysvik1 1Department of Health Studies, Faculty of Social Sciences, University of Stavanger, Stavanger, Norway; 2Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway Objective: Chronic pain is a complex, multifaceted subjective experience that involves the whole person. Self-management is the dynamic and continuous process of adapting one’s situation to the cognitive, behavioral, and emotional responses necessary to maintain a satisfactory quality of life. Approaches based on cognitive behavioral therapy (CBT are described as appropriate in assisting people suffering from chronic pain because they challenge maladaptive beliefs and behaviors in relation to pain. This study aimed to explore patients’ experiences of therapeutic elements from group participation in a chronic pain management program. Methods: A qualitative research design with a phenomenological hermeneutic approach was used. Six months after participation in the 8-week course, 34 participants formulated and submitted written reports based on open-ended questions related to their group participation and self-help achievement. These reports were analyzed by elements of qualitative content analysis. Results: The analysis resulted in two subthemes: “The significance of active involvement in gaining new insight” and “The significance of community and group support.” These were abstracted in the main theme: “Successful self-management is related to several significant contributions in the group.” Conclusion: An active role with writing, self-revelation, and exchanges of thoughts and feelings in the group seemed to be the key tools for success. In addition, group support and access to other group members’ experiences were significant therapeutic elements. We suggest that successful self-management requires knowledge of essential therapeutic elements. In a CBT

  5. Economically viable large-scale hydrogen liquefaction

    Science.gov (United States)

    Cardella, U.; Decker, L.; Klein, H.

    2017-02-01

    The liquid hydrogen demand, particularly driven by clean energy applications, will rise in the near future. As industrial large scale liquefiers will play a major role within the hydrogen supply chain, production capacity will have to increase by a multiple of today’s typical sizes. The main goal is to reduce the total cost of ownership for these plants by increasing energy efficiency with innovative and simple process designs, optimized in capital expenditure. New concepts must ensure a manageable plant complexity and flexible operability. In the phase of process development and selection, a dimensioning of key equipment for large scale liquefiers, such as turbines and compressors as well as heat exchangers, must be performed iteratively to ensure technological feasibility and maturity. Further critical aspects related to hydrogen liquefaction, e.g. fluid properties, ortho-para hydrogen conversion, and coldbox configuration, must be analysed in detail. This paper provides an overview on the approach, challenges and preliminary results in the development of efficient as well as economically viable concepts for large-scale hydrogen liquefaction.

  6. Child disaster mental health interventions, part II: Timing of implementation, delivery settings and providers, and therapeutic approaches.

    Science.gov (United States)

    Pfefferbaum, Betty; Sweeton, Jennifer L; Newman, Elana; Varma, Vandana; Noffsinger, Mary A; Shaw, Jon A; Chrisman, Allan K; Nitiéma, Pascal

    This review summarizes current knowledge on the timing of child disaster mental health intervention delivery, the settings for intervention delivery, the expertise of providers, and therapeutic approaches. Studies have been conducted on interventions delivered during all phases of disaster management from pre event through many months post event. Many interventions were administered in schools which offer access to large numbers of children. Providers included mental health professionals and school personnel. Studies described individual and group interventions, some with parent involvement. The next generation of interventions and studies should be based on an empirical analysis of a number of key areas.

  7. The Role of Simvastatin in the Therapeutic Approach of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Lucia Cojocaru

    2013-01-01

    Full Text Available The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.

  8. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zo, Jae Ill; Park, Jong Ho; Baek, Hee Jong [and others

    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 stud000.

  10. Lymphovascular and neural regulation of metastasis: Shared tumour signalling pathways and novel therapeutic approaches

    Science.gov (United States)

    Le, C.P.; Karnezis, T.; Achen, M. G.; Stacker, S.A.; Sloan, E.K.

    2014-01-01

    The progression of cancer is supported by a wide variety of non-neoplastic cell types which make up the tumour stroma, including immune cells, endothelial cells, cancer-associated fibroblasts and nerve fibres. These host cells contribute molecular signals that enhance primary tumour growth and provide physical avenues for metastatic dissemination. This article provides an overview of the role of blood vessels, lymphatic vessels and nerve fibres in the tumour microenvironment, and highlights the interconnected molecular signalling pathways that control their development and activation in cancer. Further the review highlights the known pharmacological agents which target these pathways and discusses the potential therapeutic uses of drugs that target angiogenesis, lymphangiogenesis and stress response pathways in the different stages of cancer care. PMID:24267548

  11. Mesenchymal stem cells as a therapeutic approach to glomerular diseases: benefits and risks.

    Science.gov (United States)

    Kunter, Uta; Rong, Song; Moeller, Marcus J; Floege, Jürgen

    2011-09-01

    Most studies using adult stem cells (ASCs) and progenitor cells as potential therapeutics for kidney disorders have been conducted in models of acute kidney injury, where the damage mainly affects the tubulointerstitium. The results are promising, whereas the underlying mechanisms are still being discussed controversially. Glomerular diseases have not received as much attention. Likely reasons include the often insidious onset, rendering the choice of optimal treatment timing difficult, and the fact that chronic diseases may require long-term therapy. In this mini review, we summarize current strategies in adult stem cell-based therapies for glomerular diseases. In addition, we focus on possible side effects of stem cell administration that have been reported recently, that is, profibrotic actions and maldifferentiation of mesenchymal stem cells.

  12. An integrative mechanistic account of psychological distress, therapeutic change and recovery: the Perceptual Control Theory approach.

    Science.gov (United States)

    Higginson, Sally; Mansell, Warren; Wood, Alex M

    2011-03-01

    The exact nature and mechanisms of psychological change within psychological disorders remain unknown. This review aims to use a psychological framework known as Perceptual Control Theory (Powers, 1973, 2005; Powers, Clark, & McFarland, 1960) to integrate the diverse literature within psychotherapy research. The core principles of Perceptual Control Theory are explained, and key domains of psychotherapy are considered to explore how well they converge with these principles. The quantitative and qualitative empirical literature on the process of psychological change is reviewed to examine how it fits with predictions based on Perceptual Control Theory. Furthermore, the prerequisites for psychological change; client qualities, therapist qualities, the therapeutic alliance and the shifting of awareness, are also considered to examine their consistency within a Perceptual Control Theory account. Finally the strengths and limitations of a Perceptual Control Theory account in explaining the mechanism of psychological change are considered. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Does assessing the value for money of therapeutic medical devices require a flexible approach?

    Science.gov (United States)

    Iglesias, Cynthia P

    2015-02-01

    Regulation criteria for licensing pharmaceuticals and medical devices (MDs) are asymmetric. This has affected the type, quantity and quality of the evidence produced in support of MDs. This paper has three objectives: to examine the reasons behind the current licensing criteria for MDs; to identify key methodological challenges associated with pre- and post-market evaluation of MDs and to assess the extent to which existing methods for the economic evaluation of pharmaceuticals can be applied to the evaluation of MDs. The belief that MDs cannot be properly evaluated stems from a combination of historical events and complexities in implementing rigorous RCTs in this field. Existing challenges to conduct sound economic evaluation of MDs have begun to be addressed in medical research using mixed research methods. While more challenging to implement, robust evaluations of therapeutic MDs can and need to be carried out to safeguard individual's wellbeing.

  14. 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.

  15. Stereotactic interstitial radiosurgery for intracranial Rosai-Dorfman disease. A novel therapeutic approach

    Energy Technology Data Exchange (ETDEWEB)

    El Majdoub, Faycal [Cologne Univ. (Germany). Dept. of Stereotactic and Functional Neurosurgery]|[Cologne Univ. (Germany). Dept. of General Neurosurgery; Brunn, Anna [Cologne Univ. (Germany). Dept. of Neuropathology; Berthold, Frank [Cologne Univ. (Germany). Dept. of Pediatric Oncology and Hematology; Sturm, Volker; Maarouf, Mohammad [Cologne Univ. (Germany). Dept. of Stereotactic and Functional Neurosurgery

    2009-02-15

    Rosai-Dorfman disease is an idiopathic, histoproliferative disorder characterized by massive painless lymphadenopathy. The favorable treatment of Rosai-Dorfman disease affecting the central nervous system is surgical resection. Histological and immunohistochemical confirmation is essential for a definitive diagnosis. The authors report on a 10-year-old patient with Rosai-Dorfman disease of the central nervous system who presented with increased intracranial pressure. She was treated by stereotactic interstitial irradiation using iodine-125 seeds (interstitial radiosurgery). Stereotactic surgery was performed without complications. The patient recovered well to a normal neurologic status. MR images showed a complete remission 49 months after treatment. The presented case demonstrates the high efficacy and safety of interstitial irradiation for intracranial Rosai-Dorfman disease. Hence, interstitial radiosurgery could be an appropriate therapeutic option for high-risk resectable intracranial Rosai-Dorfman disease. (orig.)

  16. Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis.

    Science.gov (United States)

    Brenton, J Nicholas; Banwell, Brenda L

    2016-01-01

    Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

  17. Hiccups. Attitude in Otorhinolaryngology Towards Consulting Patients. A Diagnostic and Therapeutic Approach.

    Science.gov (United States)

    García Callejo, Francisco Javier; Redondo Martínez, Jaume; Pérez Carbonell, Tomás; Monzó Gandía, Rafael; Martínez Beneyto, M Paz; Rincón Piedrahita, Inés

    Hiccup crises are generally benign and self-limiting, but longer episodes affect quality of life and must be treated. There are recognisable causes that otorhinolaryngologists must know and be aware for diagnosis and therapeutic alternatives. The main expression is a spasmodic glottic noise with characteristic neck alterations. This was a retrospective study from 1979 with patients suffering persistent or recurrent hiccups. Chronobiology, comorbidity, findings from explorations, therapies and outcomes were noted. Thirty-seven patients were studied (mean age, 45.5±13.5 years; 30 males), with persistent hiccups in 23 (62%). A potential associated aetiology was observed in 24 cases (65%): oesophageal disorders -mainly gastroesophageal reflux- were detected in 14 cases and concomitant oncological disease was found in 8. Only 3 cases were admitted for surgery due to these findings. Therapeutic strategies with metoclopramide were used in 18 subjects, chlorpromazine in 17 and baclofen in 13, while carbamazepine or haloperidol were used in a minority. Phrenic nerve stimulation was employed in 6 patients. Hiccups disappeared in 32 cases. Out of 22 cases for which follow-up was possible, the hiccups recurred in 5 subjects (the subjects requiring new therapies) and 11 patients died. Chronic hiccup represents a multidisciplinary challenge that includes potential head and neck affection, a diagnostic schedule for ruling out causes, frequent base oesophageal alterations and high incidence of malignant neoplasm. Prokinetic and neuroleptic agents with antidopaminergic and anticholinergic effects are the pillars of its treatment. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  18. Novel therapeutic approaches for various cancer types using a modified sleeping beauty-based gene delivery system.

    Directory of Open Access Journals (Sweden)

    In-Sun Hong

    Full Text Available Successful gene therapy largely depends on the selective introduction of therapeutic genes into the appropriate target cancer cells. One of the most effective and promising approaches for targeting tumor tissue during gene delivery is the use of viral vectors, which allow for high efficiency gene delivery. However, the use of viral vectors is not without risks and safety concerns, such as toxicities, a host immune response towards the viral antigens or potential viral recombination into the host's chromosome; these risks limit the clinical application of viral vectors. The Sleeping Beauty (SB transposon-based system is an attractive, non-viral alternative to viral delivery systems. SB may be less immunogenic than the viral vector system due to its lack of viral sequences. The SB-based gene delivery system can stably integrate into the host cell genome to produce the therapeutic gene product over the lifetime of a cell. However, when compared to viral vectors, the non-viral SB-based gene delivery system still has limited therapeutic efficacy due to the lack of long-lasting gene expression potential and tumor cell specific gene transfer ability. These limitations could be overcome by modifying the SB system through the introduction of the hTERT promoter and the SV40 enhancer. In this study, a modified SB delivery system, under control of the hTERT promoter in conjunction with the SV40 enhancer, was able to successfully transfer the suicide gene (HSV-TK into multiple types of cancer cells. The modified SB transfected cancer cells exhibited a significantly increased cancer cell specific death rate. These data suggest that our modified SB-based gene delivery system can be used as a safe and efficient tool for cancer cell specific therapeutic gene transfer and stable long-term expression.

  19. Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed.

    Science.gov (United States)

    Ando, Hidenori; Kobayashi, Sakiko; Abu Lila, Amr S; Eldin, Noha Essam; Kato, Chihiro; Shimizu, Taro; Ukawa, Masami; Kawazoe, Kazuyoshi; Ishida, Tatsuhiro

    2015-12-28

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the "fluid" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Pure Quantum Interpretations Are not Viable

    Science.gov (United States)

    Schmelzer, I.

    2011-02-01

    Pure interpretations of quantum theory, which throw away the classical part of the Copenhagen interpretation without adding new structure to its quantum part, are not viable. This is a consequence of a non-uniqueness result for the canonical operators.

  1. Return to Competition in a Chronic Low Back Pain Runner: Beyond a Therapeutic Exercise Approach, a Case Report.

    Science.gov (United States)

    Veneziani, Sergio; Doria, Christian; Falciati, Luca; Castelli, Claudio Carlo; Illic, Giorgio Fanò

    2014-09-23

    Chronic low back pain (CLBP) is a disabling condition affecting both quality of life and performance in athletes. Several approaches have been proposed in the field of physiotherapy, manual therapy, physical exercise and counseling. None apparently is outdoing the other with the exception of trunk stability exercises in specific conditions. The present paper describes a clinical success in managing a CLBP runner affected by MRI documented disk herniation via dietary change. Dietary changes allowed our patient that had failed with previous standard therapeutic approaches, to regain an optimal pain-free condition. We advance the hypothesis that a visceral-autonomic concomitant or primary disturbance possibly generating mild gastrointestinal discomfort in CLBP patients should be ruled out as a possible cause of pain and disability at the somato-motor level.

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

    Science.gov (United States)

    Verdes, Aida; Anand, Prachi; Gorson, Juliette; Jannetti, Stephen; Kelly, Patrick; Leffler, Abba; Simpson, Danny; Ramrattan, Girish; Holford, Mandë

    2016-04-19

    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.

  3. 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.

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

    DEFF Research Database (Denmark)

    Jamal, Syed Babar; Hassan, Syed Shah; Tiwari, Sandeep

    2017-01-01

    (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...

  5. Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria

    Directory of Open Access Journals (Sweden)

    V. Cenni

    2011-10-01

    Full Text Available Farnesylated prelamin A is a processing intermediate produced in the lamin A maturation pathway. Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria. Progerin elicits toxic effects in cells, leading to chromatin damage and cellular senescence and ultimately causes skin and endothelial defects, bone resorption, lipodystrophy and accelerated ageing. Knowledge of the mechanism underlying prelamin A turnover is critical for the development of clinically effective protein inhibitors that can avoid accumulation to toxic levels without impairing lamin A/C expression, which is essential for normal biological functions. Little is known about specific molecules that may target farnesylated prelamin A to elicit protein degradation. Here, we report the discovery of rapamycin as a novel inhibitor of progerin, which dramatically and selectively decreases protein levels through a mechanism involving autophagic degradation. Rapamycin treatment of progeria cells lowers progerin, as well as wild-type prelamin A levels, and rescues the chromatin phenotype of cultured fibroblasts, including histone methylation status and BAF and LAP2alpha distribution patterns. Importantly, rapamycin treatment does not affect lamin C protein levels, but increases the relative expression of the prelamin A endoprotease ZMPSTE24. Thus, rapamycin, an antibiotic belonging to the class of macrolides, previously found to increase longevity in mouse models, can serve as a therapeutic tool, to eliminate progerin, avoid farnesylated prelamin A accumulation, and restore chromatin dynamics in progeroid laminopathies.

  6. Serum 5-LOX: a progressive protein marker for breast cancer and new approach for therapeutic target.

    Science.gov (United States)

    Kumar, Rahul; Singh, Abhay Kumar; Kumar, Manoj; Shekhar, Shashank; Rai, Nitish; Kaur, Punit; Parshad, Rajinder; Dey, Sharmistha

    2016-09-01

    Lipoxygenase (LOX) pathway has emerged to have a role in carcinogenesis. There is an evidence that both 12-LOX and 5-LOX have procarcinogenic role. We have previously reported the elevated level of serum 12-LOX in breast cancer patients. This study evaluated the serum level of 5-LOX in breast cancer patients and its in vitro inhibition assessment with peptide inhibitor YWCS. The level of 5-LOX was determined by surface plasmon resonance (SPR). The peptide inhibitor of 5-LOX was designed by molecular modeling and kinetic assay was performed by spectrophotometry. The siRNA mediated 5-LOX gene silencing was performed to investigate the effect on proliferation of MDA-MB-231, breast cancer cell line. The serum 5-LOX level in breast cancer (5.69±1.97ng/µl) was almost 2-fold elevated compared to control (3.53±1.0ng/µl) (P breast cancer and a promising therapeutic target for the same. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Essential Oils Loaded in Nanosystems: A Developing Strategy for a Successful Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Anna Rita Bilia

    2014-01-01

    Full Text Available Essential oils are complex blends of a variety of volatile molecules such as terpenoids, phenol-derived aromatic components, and aliphatic components having a strong interest in pharmaceutical, sanitary, cosmetic, agricultural, and food industries. Since the middle ages, essential oils have been widely used for bactericidal, virucidal, fungicidal, antiparasitical, insecticidal, and other medicinal properties such as analgesic, sedative, anti-inflammatory, spasmolytic, and locally anaesthetic remedies. In this review their nanoencapsulation in drug delivery systems has been proposed for their capability of decreasing volatility, improving the stability, water solubility, and efficacy of essential oil-based formulations, by maintenance of therapeutic efficacy. Two categories of nanocarriers can be proposed: polymeric nanoparticulate formulations, extensively studied with significant improvement of the essential oil antimicrobial activity, and lipid carriers, including liposomes, solid lipid nanoparticles, nanostructured lipid particles, and nano- and microemulsions. Furthermore, molecular complexes such as cyclodextrin inclusion complexes also represent a valid strategy to increase water solubility and stability and bioavailability and decrease volatility of essential oils.

  8. Folklore therapeutic indigenous plants in periodontal disorders in India (review, experimental and clinical approach).

    Science.gov (United States)

    Patel, V K; Venkatakrishna-Bhatt, H

    1988-04-01

    Though a number of plants and their parts are used for dental ailments among population in rural and urban areas of developing countries, in India however, the most common house-hold, road-side plants are mango (Mangifera indica), neem (Azadirachta indica; Melia azadirachta), ocimum (Ocimum basilicum), tea-dust (Camellia sinensis) and uncommonly murayya, i.e., currey leaf (Murayya koenigi) [Chopra et al. 1958, Kirtikar and Basu 1935, Nadakarni 1954, Satyavati 1984]. The leaves of these plants are folded and brushed (massage with teadust) against the teeth. Therefore, the present study is restricted only to the fleshy leaf extracts [Jindal et al. 1975] (except tea) of these plants inspite of certain limitations in the methodology and arbitrations in the microbial identification and isolation in the light of recent advances in folk dentistry. The investigation was carried out in two parts: 1) Experimental study: The efficacy of various dentifrices (commonly available in the market) and the potentiating effect of the leaf extract (LE) of the aforesaid indigenous plants when amalgamated with the tooth-paste against pathogens, were investigated. Further, the protection afforded by the said plant extracts (PE) over the conventional allopathic medicines on the human plaque cultures and gram negative bacteria from patients were studied. 2) Clinical study: The therapeutic effects of the said PE (individually) on clinical application among severely infected patients were examined.

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

    Directory of Open Access Journals (Sweden)

    Miguel Muñoz

    2015-07-01

    Full Text Available 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.

  10. Pulmonology meets rheumatology in sarcoidosis: a review on the therapeutic approach.

    Science.gov (United States)

    Drent, Marjolein; Cremers, Johanna P; Jansen, Tim L

    2014-05-01

    Sarcoidosis is a systemic disease characterized by the formation of granulomas in various organs, mainly lungs and lymphatic system. Joint, muscle, and bone involvement is also rather common. Recent studies on its pathogenesis and therapeutic management are reviewed here. The pathogenesis of sarcoidosis is not fully elucidated. An exaggerated granulomatous reaction after exposure to unidentified antigens in genetically susceptible individuals evokes a clinical situation which we call sarcoidosis. No firm guidelines exist on whether, when, and how treatment should be started. Treatment is dependent on the presentation and the distribution, extensiveness and severity of sarcoidosis. Treatment of Löfgren's triad-related symptoms starts with NSAIDs; in other more extensive manifestations of sarcoidosis, the initiating dosage of glucocorticosteroids is approximately 20 mg daily. In terms of evidence-based treatment for sarcoidosis, only a few randomized controlled trials have been done. There is no cure for chronic sarcoidosis, and treatment only changes the granulomatous process and its clinical consequences. Identified associations of certain polymorphisms with severity of the disease and treatment response suggest future research questions as well as finding the cause(s) of sarcoidosis, and the elucidation of relevant biomarkers and new efficient treatments. Between 20 and 70% of patients need systemic therapy. The increased awareness of long-term side-effects of glucocorticosteroids and the emergence of new drugs have changed the treatment of sarcoidosis. Alternative or additional options to corticosteroids should be assessed.

  11. 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.

  12. 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.

  13. News from Tartary: an ethnopharmacological approach to drug and therapeutic discovery

    Science.gov (United States)

    Hamza, Nawel; Berke, Benedicte; Umar, Anwar

    2016-01-01

    Ethnopharmacology aims to identify new therapeutic agents based on their traditional use. It begins by the identification of disease states, and of the traditional therapies for these, most commonly herbals. Herbals of interest are selected from ethnopharmacological surveys, and tested on experimental models of the diseases of interest. Once the activity of the traditional remedy is demonstrated, including dose‐dependence, if possible comparatively to reference medications, the active ingredients can be explored, if possible using bioguided extraction. Identified molecules can then be further developed as medicinal products or pharmaceutical medicines (e.g., artemisine), or the herbal product can be developed as such (e.g. St John's wort). We provide examples of various study programmes, concerning the antiplatelet and antithrombotic effects of Armagnac extracts from Southwest France; antithrombotic and antihypertensive effects of extracts of Ocimum basilicum L; antithrombotic, antihypertensive and antihyperlipidemic effects of Cydonia oblonga; Antiproliferative and antithrombotic effects of Abnorma Savda Munziq of traditional Uyghur medicine; and the antidiabetic and hepatoprotective effects of Centaurium erythraea Rafn, Artemisia herba‐alba Asso and Trigonella foenum‐graecum L., all in collaboration between University of Bordeaux, France, Xinjiang Medical University in Urumqi, China and University Mentouri in Constantine, Algeria. PMID:27297624

  14. HIV-1 associated dementia: update on pathological mechanisms and therapeutic approaches.

    Science.gov (United States)

    Kaul, Marcus

    2009-06-01

    Infection with HIV-1 can induce dementia despite successful administration of life-prolonging highly active antiretroviral therapy. This review will discuss recent progress toward a better understanding of the pathogenesis and an improved design of therapies for HIV-associated neurocognitive disorders. Highly active antiretroviral therapy prolongs the lives of HIV patients, but the incidence of HIV-associated dementia as an AIDS-defining illness has increased and the brain is now recognized as a viral sanctuary that requires additional therapeutic effort. The neuropathology of HIV infection also has changed due to improved therapy, and while more similarities with other neurodegenerative diseases are being reported, predictive biomarkers remain elusive. However, improvements of in-vivo imaging technology and progress in uncovering the molecular mechanisms of HIV disease keep providing new insights. As such it appears that a prolonged activation of the immune system by HIV eventually leads to AIDS, and several lines of evidence indicate that simultaneously neurotoxic processes and impairment of neurogenesis both contribute to the development of HIV-associated neurocognitive disorders. The improved understanding of the interaction between HIV and its human host provides hope that adjunctive therapies to antiretroviral treatment can be developed for HIV-associated neurocognitive disorders.

  15. 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.

  16. Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure.

    Science.gov (United States)

    Boutaud, Olivier; Roberts, L Jackson

    2011-09-01

    Rhabdomyolysis-induced renal failure represents up to 15% of all cases of acute renal failure. Many studies over the past 4 decades have demonstrated that accumulation of myoglobin in the kidney is central in the mechanism leading to kidney injury. However, some discussion exists regarding the mechanism mediating this oxidant injury. Although the free-iron-catalyzed Fenton reaction has been proposed to explain the tissue injury, more recent evidence strongly suggests that the main cause of oxidant injury is myoglobin redox cycling and generation of oxidized lipids. These molecules can propagate tissue injury and cause renal vasoconstriction, two of the three main conditions associated with acute renal failure. This review presents the evidence supporting the two mechanisms of oxidative injury, describes the central role of myoglobin redox cycling in the pathology of renal failure associated with rhabdomyolysis, and discusses the value of therapeutic interventions aiming at inhibiting myoglobin redox cycling for the treatment of rhabdomyolysis-induced renal failure. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Atelectasis and mucus plugging in spinal cord injury: case report and therapeutic approaches.

    Science.gov (United States)

    Slonimski, M; Aguilera, E J

    2001-01-01

    The leading causes of morbidity and mortality in the spinal cord injury (SCI) population are airway mucus plugging and atelectasis. To illustrate the risks of pulmonary disease in individuals with SCI, and present effective therapeutic interventions. Case study of a 60-year-old veteran with T7 ASIA A spinal cord injury, who presented with a complete collapse of the left lung. This patient developed fever, sepsis, and acute renal failure following colonoscopy. Following nephrostomy to remove a calculus, chest x-ray revealed complete collapse of the left lung. Despite the severe degree of atelectasis, he exhibited only mild respiratory distress. Aggressive treatment including chest physiotherapy techniques and pharmacologic intervention (acetylcysteine; bronchodilators) resulted in significant radiographic and clinical improvement. After his return to the SCI unit, his respiratory function was monitored, and assisted cough techniques were continued. Individuals with SCI have high risk of pulmonary complications. Because of neurological deficits, the usual signs and symptoms may not be apparent. Optimal management depends upon awareness of the risks, and a thorough understanding of the pathophysiology of mucus plugging and atelectasis and the alterations in pulmonary mechanics (dependent on level of injury).

  18. Adverse effects of the renal accumulation of haem proteins. Novel therapeutic approaches.

    Science.gov (United States)

    Guerrero-Hue, Melania; Rubio-Navarro, Alfonso; Sevillano, Ángel; Yuste, Claudia; Gutiérrez, Eduardo; Palomino-Antolín, Alejandra; Román, Elena; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2017-06-28

    Haemoglobin and myoglobin are haem proteins that play a key role as they help transport oxygen around the body. However, because of their chemical structure, these molecules can exert harmful effects when they are released massively into the bloodstream, as reported in certain pathological conditions associated with rhabdomyolysis or intravascular haemolysis. Once in the plasma, these haem proteins can be filtered and can accumulate in the kidney, where they become cytotoxic, particularly for the tubular epithelium, inducing acute kidney failure and chronic kidney disease. In this review, we will analyse the different pathological contexts that lead to the renal accumulation of these haem proteins, their relation to both acute and chronic loss of renal function, the pathophysiological mechanisms that cause adverse effects and the defence systems that counteract such actions. Finally, we will describe the different treatments currently used and present new therapeutic options based on the identification of new cellular and molecular targets, with particular emphasis on the numerous clinical trials that are currently ongoing. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jeroen Bremer

    2016-01-01

    Full Text Available 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.

  20. 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.

  1. Smooth muscle myosin inhibition: a novel therapeutic approach for pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    David Ho

    Full Text Available Pulmonary hypertension remains a major clinical problem despite current therapies. In this study, we examine for the first time a novel pharmacological target, smooth muscle myosin, and determine if the smooth muscle myosin inhibitor, CK-2019165 (CK-165 ameliorates pulmonary hypertension.Six domestic female pigs were surgically instrumented to measure pulmonary blood flow and systemic and pulmonary vascular dynamics. Pulmonary hypertension was induced by hypoxia, or infusion of the thromboxane analog (U-46619, 0.1 µg/kg/min, i.v.. In rats, chronic pulmonary hypertension was induced by monocrotaline.CK-165 (4 mg/kg, i.v. reduced pulmonary vascular resistance by 22±3 and 28±6% from baseline in hypoxia and thromboxane pig models, respectively (p<0.01 and 0.01, while mean arterial pressure also fell and heart rate rose slightly. When CK-165 was delivered via inhalation in the hypoxia model, pulmonary vascular resistance fell by 17±6% (p<0.05 while mean arterial pressure and heart rate were unchanged. In the monocrotaline model of chronic pulmonary hypertension, inhaled CK-165 resulted in a similar (18.0±3.8% reduction in right ventricular systolic pressure as compared with sildenafil (20.3±4.5%.Inhibition of smooth muscle myosin may be a novel therapeutic target for treatment of pulmonary hypertension.

  2. 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.

  3. 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...

  4. Targeting the notch pathway: A potential therapeutic approach for desmoid tumors

    OpenAIRE

    Shang, Hui; Braggio, Danielle; Lee, Ya?Jung; Al Sannaa, Ghadah A.; Creighton, Chad J.; Bolshakov, Svetlana; Lazar, Alexander J.F.; Lev, Dina; Pollock, Raphael E.

    2015-01-01

    BACKGROUND Desmoid tumors (DTs) are rare mesenchymal lesions that can recur repeatedly. When it is feasible, DTs are surgically resected; however, this often results in high recurrence rates. Recently, treatment with PF?03084014, a potent ??secretase inhibitor, has been shown to have antitumor activity in several tumor types by affecting the WNT/??catenin pathway. Consequently, Notch pathway inhibition by PF?03084014 might be a promising approach for DT treatment. METHODS The expression of No...

  5. 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

  6. Varicosities of the lower extremity, new approaches: cosmetic or therapeutic needs?

    Science.gov (United States)

    Spinedi, Luca; Uthoff, Heiko; Partovi, Sasan; Staub, Daniel

    2016-01-01

    Varicose veins of the lower extremity (VVLE) are a frequently encountered vascular disorder in the general population. The general view that VVLE are a non-serious disease with primarily aesthetic impact is a common misconception, as the disease can have a significant negative impact on generic and disease-specific quality of life. Further, VVLE may be associated with potentially threatening clinical conditions, such as chronic venous ulceration, venous thromboembolism and haemorrhage from ruptured varicose veins. In the case of symptomatic varicose veins, in the presence of advanced lower limb skin changes or when venous complications occur, a referral for dedicated evaluation by the vascular medicine specialist is recommended. The initial diagnostic test of choice to detect the extent of the varicose disease and to plan treatment is duplex ultrasound. Traditionally, compression therapy, surgical high ligation and stripping of the truncal veins have been considered standard of care for VVLE. Driven by the aim to reduce surgical trauma and improve the long-term effectiveness, minimally invasive treatment options have been developed in the last two decades, namely endovascular vein ablation techniques (EVA). Endovenous laser ablation and radiofrequency ablation have been established as first-line treatments for varicose veins associated with axial reflux on the basis of the most recent international guidelines. For practical purposes and depending on the concrete clinical situation, the various EVA and surgical techniques are often combined, leading to multimodal varicose vein therapy management. Knowledge of the different techniques is of utmost importance for the vascular medicine specialist. The purpose of this article is to provide an overview of the new EVA techniques and to elucidate the different therapeutic strategies for VVLE.

  7. Diagnostic and therapeutic approaches for nonmetastatic breast cancer in Canada, and their associated costs

    Science.gov (United States)

    Will, B P; Petit, C Le; Berthelot, J-M; Tomiak, E M; Verma, S; Evans, W K

    1999-01-01

    In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and treat serious illnesses. As breast cancer is the major malignancy affecting Canadian women, Statistics Canada has analysed the resources required to manage this disease in Canada, and the associated costs. Here we report the cost of initial diagnosis and treatment of nonmetastatic breast cancer, including adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease were derived by age group (calculated for a cohort of 17 700 Canadian women diagnosed in 1995. Early stage (Stages I and II) breast cancer represented 87% of all incident cases, with 77% of cases occurring in women ≥ 50 years. Variations were noted in the rate of partial vs total mastectomy, according to stage and age group. Direct costs for diagnosis and initial treatment ranged from $8014 for Stage II women ≥ 50 years old, to $10 897 for Stage III women < 50 years old. Except for Stage III women < 50 years old, the largest expenditure was for hospitalization for surgery, followed by radiotherapy costs. Chemotherapy was the largest cost component for Stage III women < 50 years old. This report describes the cost of diagnosis and initial treatment of nonmetastatic breast cancer in Canada, assuming current practice patterns. A second report will describe the lifetime costs of treating all stages of breast cancer. These data will then be incorporated into Statistics Canada's Population Health Model (POHEM) to perform cost-effectiveness studies of new therapeutic interventions for breast cancer, such as the cost-effectiveness of day surgery, or of radiotherapy to all breast cancer patients undergoing breast surgery. © 1999 Cancer Research Campaign PMID:10188886

  8. Serenoa Repens, lycopene and selenium: a triple therapeutic approach to manage benign prostatic hyperplasia.

    Science.gov (United States)

    Minutoli, L; Bitto, A; Squadrito, F; Marini, H; Irrera, N; Morgia, G; Passantino, A; Altavilla, D

    2013-01-01

    Benign prostatic hyperplasia (BPH) is a major health concern that is likely to have an increasing impact in line with the gradual aging of the population. BPH is characterized by smooth muscle and epithelial proliferation primarily within the prostatic transition zone that can cause a variety of problems for patients, the most frequent are the lower urinary tract symptoms. BPH is thought to involve in disruption of dihydrotestosterone (DHT)-supported homeostasis between cell proliferation and cell death, and, as a result, proliferative processes predominate and apoptotic processes are inhibited. Phytotherapeutic supplements, mainly based on Saw Palmetto-derived Serenoa Repens (SeR), are numerous and used frequently. Serenoa Repens reduces inflammation and decreases in vivo the androgenic support to prostatic cell growth. Furthermore, SeR stimulates the apoptotic machinery; however, data supporting efficacy is limited, making treatment recommendations difficult. Besides SeR, selenium (Se), an essential trace element mainly functioning through selenoproteins and able to promote an optimal antioxidant/oxidant balance, and lycopene (Ly), a dietary carotenoid synthesized by plants, fruits, and microorganisms with a strong antioxidant activity, has been shown to exert beneficial effects in prostate disease. SeR is frequently associated with Ly and Se, in order to increase its therapeutic activity in benign prostatic hyperplasia (BPH). It has been shown that the Ly-Se-SeR association has a greater and enhanced antiinflammatory activity that might be of particular interest in the treatment of BPH. The Ly-Se-SeR association is also more effective than SeR alone in reducing prostate weight and hyperplasia, in augmenting the pro-apoptotic Bax and caspase-9 and blunting the anti-apoptotic Bcl-2 mRNA. In addition, Ly-Se-SeR more efficiently suppresses the EGF and Vascular Endothelial Growth Factor (VEGF) expressions in hyperplastic prostates. Therefore, SeR particularly when

  9. Diagnostic and Therapeutic Approach in a Case of Severe Post-Traumatic Hyphema with Subtotal Iridodialysis

    Directory of Open Access Journals (Sweden)

    Filippo Romanazzi

    2017-10-01

    Full Text Available Purpose: To report our diagnostic ultrasound-based approach and surgical strategy in a case of severe blunt trauma with complete hyphema, 270° iris disinsertion, and traumatic subluxated cataract. Case Report: A 70-year-old male was referred to our hospital for a blunt trauma in his right eye. A complete examination revealed visual acuity consisting in light perception, a complete hyphema, and an intraocular pressure of 45 mm Hg with moderate pain. Our diagnostic approached was ultrasound based with B-scan examination showing some vitreous hemorrhage and ultrasound biomicroscopy showing a large iris disinsertion of 270° with the iris entirely dislocated in the inferior sector of the anterior chamber. The patient was hospitalized and a systemic and topical treatment was started to lower intraocular pressure. Our surgery consisted in a single-step approach with removal of traumatic cataract with scleral fixation of an intraocular lens and iridoplasty. Conclusion: In our patient, the single-step surgery, supported by anterior and posterior ultrasound imaging, achieved a satisfactory anatomical and functional outcome.

  10. 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.

  11. Diagnostic and therapeutic approach to coexistent chronic obstructive pulmonary disease and obstructive sleep apnea

    Science.gov (United States)

    Jelic, Sanja

    2008-01-01

    The high prevalence of both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in Western societies is well documented. However, OSA frequently remains unrecognized and untreated among patients with COPD. Patients with both conditions have a greater risk for fatal and nonfatal cardiovascular events compared with patients with COPD or OSA alone. Efficacious treatment with continuous positive airway pressure reduces the risk of cardiovascular complications in patients with OSA. The aim of the present review is to discuss the diagnostic approach to patients with both conditions and to delineate the benefits of timely recognition and treatment of OSA in patients with COPD. PMID:18686735

  12. Therapeutic approaches to slowing the progression of diabetic nephropathy – is less best?

    Directory of Open Access Journals (Sweden)

    Eva Vivian

    2013-03-01

    Full Text Available Objective: Angiotensin II receptor blockers (ARBs and angiotensin-converting enzyme (ACE inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin–angiotensin–aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI, to monotherapy.Design: Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012 and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs.Setting: Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review.Participants: Adult (≥18 years patients with diabetic nephropathy.Measurements: Serum creatinine level was used to estimate glomerular filtration rate (GFR. GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine was defined as macroalbuminuria.Results: ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk

  13. Therapeutic approaches to slowing the progression of diabetic nephropathy - is less best?

    Science.gov (United States)

    Vivian, Eva; Mannebach, Chelsea

    2013-03-27

    Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin-angiotensin-aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI), to monotherapy. Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012) and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs. Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review. Adult (≥18 years) patients with diabetic nephropathy. Serum creatinine level was used to estimate glomerular filtration rate (GFR). GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine) was defined as macroalbuminuria. ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk of hyperkalemia or acute kidney injury. Both ACE inhibitors and ARBs remain

  14. Therapeutic approaches to slowing the progression of diabetic nephropathy – is less best?

    Science.gov (United States)

    Vivian, Eva; Mannebach, Chelsea

    2013-01-01

    Objective: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin–angiotensin–aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI), to monotherapy. Design: Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012) and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs. Setting: Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review. Participants: Adult (≥18 years) patients with diabetic nephropathy. Measurements: Serum creatinine level was used to estimate glomerular filtration rate (GFR). GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine) was defined as macroalbuminuria. Results: ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk of

  15. Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice.

    Science.gov (United States)

    Fermoselle, Clara; García-Arumí, Elena; Puig-Vilanova, Ester; Andreu, Antoni L; Urtreger, Alejandro J; de Kier Joffé, Elisa D Bal; Tejedor, Alberto; Puente-Maestu, Luís; Barreiro, Esther

    2013-09-01

    muscle strength, decreased activity of complexes I, II and IV and decreased oxygen consumption in both muscles. Blockade of nuclear factor-κB and MAPK actions restored muscle mass and force and corrected the MRC dysfunction in both muscles, while partly reducing tumour burden. Antioxidants improved mitochondrial oxygen uptake without eliciting significant effects on the loss of muscle mass and force or tumour size, whereas the proteasome inhibitor reduced tumour burden without significantly influencing muscle mass and strength or mitochondrial function. In conclusion, nuclear factor-κB and MAPK signalling pathways modulate muscle mass and performance and MRC function of respiratory and limb muscles in this model of experimental cancer cachexia, thus offering targets for therapeutic intervention.

  16. Cybernetically sound organizational structures II: Relating de Sitter's design theory to Beer's viable system model

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.; Vriens, D.J.

    2011-01-01

    - Purpose – The purpose of this paper is to show how the viable system model (VSM) and de Sitter's design theory can complement each other in the context of the diagnosis and design of viable organizations. - Design/methodology/approach – Key concepts from Beer's model and de Sitter's design

  17. 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.

  18. MANAGEMENT OF ENDOCRINE DISEASE: Diagnostic and therapeutic approach of tall stature.

    Science.gov (United States)

    Albuquerque, Edoarda V A; Scalco, Renata C; Jorge, Alexander A L

    2017-06-01

    Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Tall individuals are usually referred to endocrinologists so that hormonal disorders leading to abnormal growth are excluded. However, the majority of these patients have familial tall stature or constitutional advance of growth (generally associated with obesity), both of which are diagnoses of exclusion. It is necessary to have familiarity with a large number of rarer overgrowth syndromes, especially because some of them may have severe complications such as aortic aneurysm, thromboembolism and tumor predisposition and demand-specific follow-up approaches. Additionally, endocrine disorders associated with tall stature have specific treatments and for this reason their recognition is mandatory. With this review, we intend to provide an up-to-date summary of the genetic conditions associated with overgrowth to emphasize a practical diagnostic approach of patients with tall stature and to discuss the limitations of current growth interruption treatment options. © 2017 European Society of Endocrinology.

  19. A novel strategy to develop therapeutic approaches to prevent proliferative vitreoretinopathy.

    Science.gov (United States)

    Pennock, Steven; Rheaume, Marc-Andre; Mukai, Shizuo; Kazlauskas, Andrius

    2011-12-01

    Proliferative vitreoretinopathy (PVR) thwarts the repair of rhegmatogenous retinal detachments. Currently, there is no effective prevention for PVR. Platelet-derived growth factor receptor α (PDGFRα) is associated with PVR in humans and strongly promotes experimental PVR driven by multiple vitreal growth factors outside the PDGF family. We sought to identify vitreal factors required for experimental PVR and to establish a potential approach to prevent PVR. Vitreous was obtained from normal rabbits or those in which PVR was either developing or stabilized. Normal vitreous contained substantial levels of growth factors and cytokines, which changed quantitatively and/or qualitatively as PVR progressed and stabilized. Neutralizing a subset of these agents in rabbit vitreous eliminated their ability to induce PVR-relevant signaling and cellular responses. A single intravitreal injection of neutralizing reagents for this subset prevented experimental PVR. To identify growth factors and cytokines likely driving PVR in humans, we subjected vitreous from patients with or without PVR to a similar series of analyses. This analysis accurately identified those agents required for vitreous-induced contraction of cells from a patient PVR membrane. We conclude that combination therapy encompassing a subset of vitreal growth factors and cytokines is a potential approach to prevent PVR. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Telephonic voice intelligibility after laryngeal cancer treatment: is therapeutic approach significant?

    Science.gov (United States)

    Crosetti, Erika; Fantini, Marco; Arrigoni, Giulia; Salonia, Laura; Lombardo, Agata; Atzori, Alessio; Panetta, Valentina; Schindler, Antonio; Bertolin, Andy; Rizzotto, Giuseppe; Succo, Giovanni

    2017-01-01

    The aim was to investigate telephonic voice intelligibility in patients treated for laryngeal cancer using different approaches. In total, 90 patients treated for laryngeal cancer using different approaches and 12 healthy volunteers were recruited. Each patient and each healthy control read a list of words and sentences during a telephone call. Six auditors listened to each telephonic recording and transcribed the words and sentences they understood. Mean intelligibility rates for each treatment were assessed and compared. Regarding words, the poorest intelligibility was noted for type II open partial horizontal laryngectomies, followed by total laryngectomies. The best intelligibility was found for transoral laser microsurgery, followed by radiotherapy alone. For sentences, the poorest intelligibility was noted for type II open partial horizontal laryngectomies, followed by chemoradiotherapy. The best intelligibility was found for radiotherapy alone and transoral laser microsurgery. More aggressive surgery as well as chemoradiotherapy correlated with significantly poorer outcomes. Transoral laser microsurgery or radiotherapy alone ensured the best telephonic voice intelligibility. Intermediate-advanced T stages at diagnosis also showed significantly poorer intelligibility outcomes, suggesting that T stage represents an independent negative prognostic factor for voice intelligibility after treatment.

  1. A new approach to the study of therapeutic work in the transference.

    Science.gov (United States)

    Pessier, J; Stuart, J

    2000-02-01

    This article proposes a new method for evaluating the effects of therapist and patient work in the transference. Work in the transference is often difficult for the patient, and may show a characteristic pattern of lag between a transference interpretation and its therapeutic effect. To account for this lag, we assessed patient responses to interpretations over the course of entire sessions. The narratives patients told about others, or Relationship Episodes (REs), were used as units of study. In a sample of three consecutive sessions taken from each of three psychodynamic cases, we identified several instances when transference work appeared to have an initial inhibitory effect, but facilitated progress over the course of the entire session. We recommend that to examine the effects of interpretations future studies use longer, more clinically meaningful segments of patient speech than have been used in the past. Dieser Beitrag propagiert eine neue Methode zur Evaluierung der Effekte von Übertragungsarbeit durch Therapeut und Patient. Arbeit in der Übertragung ist für den Patienten oftmals schwierig und zeigt häufig eine charakteristisches Muster von zeitlichen Verzögerungen bzgl. Übertragungsdeutungen und deren therapeutischen Effekten. Um diese zeitliche Verzögerung zu erklären, untersuchten wir die Reaktionen von Patienten auf derartige Deutungen im Verlauf ganzer Sitzungen. Narrative, in denen die Patienten über andere berichteten, also Beziehungsepisoden, dienten in dieser Studie als Einheit. In einter Stichprobe dreier aufeinanderfolgender Sitzugnen, die sich auf drei Fälle bezogen, identifizierten wir verschiedene Umstände, unter denen Übertragungsarbeit anfänglich einen hemmenden Affekt zu haben schien, letztlich aber den Gesamtverlauf der Sitzung günstig beeinflussten. Wir empfehlen, in Zukunft die Effekte von Übertragungsdeutungen auf der Basis längerer, klinische sinnvoller Segmente von Patientenäußerungen zu untersuchen als dies in der

  2. A generic sample preparation approach for LC–MS/MS bioanalysis of therapeutic monoclonal antibodies in serum applied to Infliximab

    Directory of Open Access Journals (Sweden)

    Anne J. Kleinnijenhuis

    2015-01-01

    Full Text Available In this study, we developed a generic bioanalytical workflow providing sensitive, specific, and accurate absolute quantification of therapeutic monoclonal antibodies in serum. The workflow involves magnetic beads coated with protein A to pull-down therapeutic monoclonal antibodies with affinity for protein A from the biological matrix, followed by tryptic digestion and LC-MS/MS quantification of a unique signature peptide, considering of course the matrix of interest and other present mAbs, if applicable. The feasibility of this approach was demonstrated for Infliximab (trade name Remicade in rat serum. The assigned signature peptide was monitored in the selected reaction monitoring (SRM mode. Assay variability was determined to be below 20%, except at the QC low level, which was provided through optimization of the sample preparation and monitoring of the LC-MS/MS using a stable isotope labeled signature peptide as internal standard. The 100 ng/ml lower limit of quantification using only 25 μl sample volume, is generally considered as sufficient for pharmaceutical development purposes for monoclonal antibodies.

  3. 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.

  4. 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.

  5. Diagnostic and therapeutic approach to coexistent chronic obstructive pulmonary disease and obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Sanja Jelic

    2008-06-01

    Full Text Available Sanja JelicDivision of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USAAbstract: The high prevalence of both obstructive sleep apnea (OSA and chronic obstructive pulmonary disease (COPD in Western societies is well documented. However, OSA frequently remains unrecognized and untreated among patients with COPD. Patients with both conditions have a greater risk for fatal and nonfatal cardiovascular events compared with patients with COPD or OSA alone. Efficacious treatment with continuous positive airway pressure reduces the risk of cardiovascular complications in patients with OSA. The aim of the present review is to discuss the diagnostic approach to patients with both conditions and to delineate the benefits of timely ecognition and treatment of OSA in patients with COPD.Keywords: chronic obstructive pulmonary disease, obstructive sleep apnea, continuous positive airway pressure, nocturnal arterial oxyhemoglobin desaturation

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

    Science.gov (United States)

    Mazzoleni, Stefano; Duret, Christophe; Grosmaire, Anne Gaëlle; Battini, Elena

    2017-01-01

    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.

  7. Educational and therapeutic behavioral approaches to providing dental care for patients with Autism Spectrum Disorder.

    Science.gov (United States)

    Nelson, Travis M; Sheller, Barbara; Friedman, Clive S; Bernier, Raphael

    2015-01-01

    Autism Spectrum Disorder (ASD) is a condition which most dentists will encounter in their practices. Contemporary educational and behavioral approaches may facilitate successful dental care. A literature review was conducted for relevant information on dental care for children with ASD. Educational principles used for children with ASD can be applied in the dental setting. Examples include: parent involvement in identifying strengths, sensitivities, and goal setting; using stories or video modeling in advance of the appointment; dividing dental treatment into sequential components; and modification of the environment to minimize sensory triggers. Patients with ASD are more capable of tolerating procedures that they are familiar with, and therefore should be exposed to new environments and stimuli in small incremental steps. By taking time to understand children with ASD as individuals and employing principles of learning, clinicians can provide high quality dental care for the majority of patients with ASD. © 2014 Special Care Dentistry Association and Wiley Periodicals, Inc.

  8. Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches.

    Science.gov (United States)

    Sahin, Ibrahim H; Lowery, Maeve A; Stadler, Zsofia K; Salo-Mullen, Erin; Iacobuzio-Donahue, Christine A; Kelsen, David P; O'Reilly, Eileen M

    2016-08-01

    Pancreatic cancer is one of the most challenging cancers. Whole genome sequencing studies have been conducted to elucidate the underlying fundamentals underscoring disease behavior. Studies have identified a subgroup of pancreatic cancer patients with distinct molecular and clinical features. Genetic fingerprinting of these tumors is consistent with an unstable genome and defective DNA repair pathways, which creates unique susceptibility to agents inducing DNA damage. BRCA1/2 mutations, both germline and somatic, which lead to impaired DNA repair, are found to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Recent studies have elucidated that PARP inhibitors and platinum agents may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. In this review we discuss the characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as a novel treatment approach.

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

    Science.gov (United States)

    Grosmaire, Anne Gaëlle; Battini, Elena

    2017-01-01

    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. PMID:29057269

  10. Unmet Therapeutic Needs: Focus on Intestinal Fibrosis Surgical Approach: Resection, Strictureplasty and Others.

    Science.gov (United States)

    Mege, Diane; Panis, Yves

    2017-01-01

    In patients with ileo-colonic Crohn's disease (CD), the main consequence of the development of intestinal fibrosis is the occurrence of a localized symptomatic stenosis for which treatment is mandatory. Besides medical treatment, which is still considered to be ineffective against non-inflammatory fibrotic intestinal stenosis due to CD, there are 2 options for the treatment of such stenosis: endoscopic and surgical approaches. Key Messages: Endoscopic treatment includes balloon dilatation and stenting, and can be performed only on selected patients with very short stenosis. Few reports with a small sample size are available; long-term results of endoscopic treatment remain unknown, with patients being exposed to possible early recurrence of the stenosis. For this reason, intestinal resection currently remains the first option for localized symptomatic intestinal stenosis due to CD refractory to medical therapy. Laparoscopic ileocecal resection with ileocolonic anastomosis gives good short-term results, without mortality and with very low rate of morbidity. Furthermore, when the resection is shorter than 50 cm, very few functional consequences or no consequences are reported, and quality of life is improved. However, CD recurrence is frequent and can be required to redo surgery in up to 30% of the cases. In order to reduce the theoretical risk of short bowel syndrome, some surgeons have proposed strictureplasty as a more conservative approach. The concept is to treat stenosis without intestinal resection by opening the stenosis. There are different kinds of stricturoplasty, with similar reported morbidity and long-term recurrence rates than those observed with resection. Because no randomized study exists, it is difficult to know what the best option for symptomatic ileal stenosis in CD is. However, for a majority of patients today, ileocecal resection is the first option, strictureplasty being reserved by most of the surgeons for recurrent cases and/or multiple

  11. Modulation of Notch signaling as a therapeutic approach for liver cancer.

    Science.gov (United States)

    Wu, Guang; Wilson, George; George, Jacob; Qiao, Liang

    2015-01-01

    Notch signaling is an evolutionarily conserved pathway crucial for the development and homeostasis of many organs including liver. Aberrant Notch signaling has been mechanistically linked to cancer development including liver cancer. The two principal types of liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). HCCs comprise over 80% of all liver cancers and are the 6(th) most common malignancy worldwide. Hepatocellular carcinoma is also a cancer with an extremely poor prognosis, being the 3(rd) commonest cause of cancer-related mortality. Accumulating evidence indicates that the role of Notch signaling in liver cancer is more complex than once thought and is dependent on the expression of specific Notch signaling components and the complex crosstalk with other signaling pathways. Currently there are a variety of gene therapy based approaches used to target Notch signaling in preclinical studies to successfully treat liver cancer including neutralizing antibodies, siRNA, shRNA and miRNA. The use of targeted anti-Notch therapy in the clinic to treat liver cancer will require considerable refinement of our current knowledge on the regulation of Notch signaling components and their effects in both normal and malignant liver cells in order to target specific Notch subunits which are critical to liver cancer tumorigenesis but not to the homeostasis of normal cells. Using this approach will reduce the major side effects, which are frequently seen in patients treated with GSIs to inhibit the entire Notch signaling pathway. Here our understanding of Notch signaling is reviewed, highlighting its function in liver cancer initiation, progress and opportunities for liver cancer therapies.

  12. Phase-dependent modulation as a novel approach for therapeutic brain stimulation

    Directory of Open Access Journals (Sweden)

    Ramin eAzodi-Avval

    2015-02-01

    Full Text Available Closed-loop paradigms provide us with the opportunity to optimize stimulation protocols for perturbation of pathological oscillatory activity in brain-related disorders. In this vein, spiking activity of motor cortex neurons and beta activity of local field potentials in the subthalamic nucleus have both been used independently of each other as neuronal signals to trigger deep brain stimulation for alleviating Parkinsonism. These approaches were superior to the standard continuous high-frequency stimulation protocols used in daily practice. However, they achieved their effects by bursts of stimulation that were applied at high-frequency as well, i.e. independent of the phase information in the stimulated region. In this context, we propose that, by timing stimulation pulses relative to the ongoing oscillation, an alternative approach, namely the targeted perturbation of pathological rhythms, could be obtained.In this modeling study, we first captured the underlying dynamics of neuronal oscillations in the human subthalamic nucleus by phased coupled neuronal oscillators. We then quantified the nature of the interaction between these coupled oscillators by obtaining a physiologically informed phase response curve from local field potentials. Reconstruction of the phase response curve predicted the sensitivity of the phase oscillator to external stimuli, revealing phase intervals that optimally maximized the degree of perturbation. We conclude that our specifically timed intervention based on the coupled oscillator concept will enable us to identify personalized ways of delivering stimulation pulses in closed-loop paradigms triggered by the phase of pathological oscillations. This will pave the way for novel physiological insights and substantial clinical benefits. In addition, this precisely phased modulation may be capable of modifying the effective interactions between oscillators in an entirely new manner.

  13. 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.

  14. 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.

  15. Photothermal sensitisation as a novel therapeutic approach for tumours: studies at the cellular and animal level.

    Science.gov (United States)

    Camerin, Monica; Rello, Santiago; Villanueva, Angeles; Ping, Xinzhan; Kenney, Malcolm E; Rodgers, Michael A J; Jori, Giulio

    2005-05-01

    Irradiation of B78H1 murine amelanotic melanoma cells with 850 nm light emitted from a Ti:sapphire laser, operated in a pulsed mode at high fluence rates and in the presence of Ni(II)-octabutoxy-naphthalocyanine (NiNc), promoted a photothermally sensitised process leading to fast and irreversible cell death. This resulted in the ejection of a consistent mass of cytoplasmic material from the irradiated cells that was detected by scanning electron microscopy. The extensive chemical and mechanical damage was probably caused by the photoinduced generation of an acoustic shock wave. The efficiency of the photoprocess was modulated by intracellular concentration of NiNc and maximally by the formation of aggregated naphthalocyanine clusters in specific subcellular areas. Very similar results were obtained upon irradiation of NiNc-loaded C32 human amelanotic melanoma cells and transformed murine HT-1080 and HaCaT fibroblasts. From these results, photothermal sensitisation appears to be a general phenomenon and preliminary studies with mice bearing subcutaneously transplanted amelanotic melanomas, irradiated with 850 nm light 24 h after intravenous injection of NiNc, suggest that this approach has potential for the therapy of some types of skin tumours.

  16. 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.

  17. 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.

  18. Feasibility of nonsense mutation readthrough as a novel therapeutical approach in propionic acidemia.

    Science.gov (United States)

    Sánchez-Alcudia, Rocío; Pérez, Belén; Ugarte, Magdalena; Desviat, Lourdes R

    2012-06-01

    Aminoglycosides and other compounds can promote premature termination codon (PTC) readthrough constituting a potential therapy for patients with nonsense mutations. In a cohort of 190 propionic acidemia (PA) patients, we have identified 12 different nonsense mutations, six of them novel, accounting for 10% of the mutant alleles. Using an in vitro system, we establish the proof-of-principle that nonsense mutations in the PCCA and PCCB genes encoding both subunits of the propionyl-CoA carboxylase (PCC) enzyme can be partially suppressed by aminoglycosides, with different efficiencies depending on the sequence context. To correct the metabolic defect, the amino acid incorporated at the PTC should support protein function, and this has been evaluated in silico and by in vitro expression analysis of the predicted missense changes, most of which retain partial activity, confirming the feasibility of the approach. In patients' fibroblasts cultured with readthrough drugs, we observe a fourfold to 50-fold increase in the PCC activity, reaching up to 10-15% level of treated control cells. The ability to partially correct nonsense PCCA and PCCB alleles represents a potential therapy or supplementary treatment for a number of propionic acidemia (PA) patients, encouraging further clinical trials with readthrough drugs without toxic effects such as PTC124 or other newly developed compounds. Hum Mutat 33:973-980, 2012. © 2012 Wiley Periodicals, Inc. © 2012 Wiley Periodicals, Inc.

  19. Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Manfredi Rizzo

    2013-03-01

    Full Text Available Small, dense low density lipoprotein (sdLDL represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG, very low density lipoprotein (VLDL and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk.

  20. The potential role of nanotechnology in therapeutic approaches for triple negative breast cancer.

    Science.gov (United States)

    Johnson, Rebecca; Sabnis, Nirupama; McConathy, Walter J; Lacko, Andras G

    2013-01-01

    Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression of the human epidermal growth factor receptor 2 (HER2). It is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. Unfortunately, TNBC patients do not benefit from current anti-HER2 or hormone positive targeted breast cancer treatments; consequently, these patients rely primarily on chemotherapy. However, the 5-year survival rate for woman with metastatic TNBC is less than 30%. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and <2% respectively. Because the only current systemic treatment for TNBC is chemotherapy, alternative targeted therapies are urgently needed to improve the prognosis for TNBC patients. This review is focused on opportunities for developing new approaches for filling the current void in an effective treatment for TNBC patients.

  1. The Potential Role of Nanotechnology in Therapeutic Approaches for Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Andras G. Lacko

    2013-06-01

    Full Text Available Triple Negative Breast Cancer, TNBC, a highly aggressive and metastatic type of breast cancer, is characterized by loss of expression of the estrogen receptor (ER, progesterone receptor (PR, and a lack of overexpression of the human epidermal growth factor receptor 2 (HER2. It is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. Unfortunately, TNBC patients do not benefit from current anti-HER2 or hormone positive targeted breast cancer treatments; consequently, these patients rely primarily on chemotherapy. However, the 5-year survival rate for woman with metastatic TNBC is less than 30%. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and <2% respectively. Because the only current systemic treatment for TNBC is chemotherapy, alternative targeted therapies are urgently needed to improve the prognosis for TNBC patients. This review is focused on opportunities for developing new approaches for filling the current void in an effective treatment for TNBC patients.

  2. Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review)

    Science.gov (United States)

    Tse, Gary; Liu, Tong; Li, Ka Hou Christien; Laxton, Victoria; Wong, Andy On-Tik; Chan, Yin Wah Fiona; Keung, Wendy; Chan, Camie W.Y.; Li, Ronald A.

    2017-01-01

    Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia-bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene-based bio-artificial sinoatrial node and cell-based bio-artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three-way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies. PMID:28204831

  3. A convenient approach to facilitate monitoring Gaucher disease progression and therapeutic response.

    Science.gov (United States)

    Zhang, Wujuan; Oehrle, Melissa; Prada, Carlos E; Schwartz, Ida Vanessa D; Chutipongtanate, Somchai; Wattanasirichaigoon, Duangrurdee; Inskeep, Venette; Dai, Mei; Pan, Dao; Sun, Ying; Setchell, Kenneth D R

    2017-09-08

    Gaucher disease (GD) is caused by mutations on the GBA1 gene leading to deficiency in acid β-glucosidase (GCase) and subsequent accumulation of its substrates, glucosylceramide (GlcC) and glucosylsphingosine (GlcS). GlcS in plasma has been proposed as a highly sensitive and specific biomarker for the diagnosis of GD and for monitoring disease progression and response to therapy. Here we report a novel robust and accurate hydrophilic interaction liquid chromatography tandem mass spectrometric method (HILIC-MS/MS) for the direct measurement of glucosylsphingosine (GlcS) in dried plasma spots (DPS). The method was also capable of resolving the isomeric pair, glucosylsphingosine and galactosylsphingosine, the latter of which was proposed as a promising biomarker for Krabbe disease. The method was fully validated and applied to the analysis of 19 GD patients and carriers. The GlcS levels in 9 GD type I patients who have been on enzyme replacement therapy (ERT) were reduced to a mean of 31.0 nM, much lower compared to a pre-treated specimen at a level of 85.8 nM, but still significantly elevated compared to healthy controls. GlcS concentrations in three treated type III GD patients were much lower compared to an untreated patient. In our preclinical GD studies, 4L;C* mice (subacute nGD model) exhibited comparable levels of plasma GlcS, but had much higher GlcS accumulation in the brain than those of 9V/null mice (chronic neuropathic GD model). Our method for the measurement of GlcS in DPS proved to be a very convenient approach for sample collection, storage and shipping nationwide and internationally.

  4. Ovarian and oviductal pathologies in the buffalo: Occurrence, diagnostic and therapeutic approaches

    Directory of Open Access Journals (Sweden)

    G N Purohit

    2014-06-01

    Full Text Available Ovarian pathologies observed in the buffalo include developmental anomalies, inflammatory conditions and neoplasm's, the usual incidence of which has been observed to be low (0.1%–19.0% in abattoir studies. Ovarian functional disorders are the most frequently observed clinical entities in buffalo and include conditions such as sub estrus, (7.4%–55.8%, persistent corpus luteum (0.54% and ovarian cysts (0.5%–1.4%. The diagnostic approaches for ovarian hypofunction and ovarian pathologies include transrectal palpation and transrectal ultrasonography the efficiency of which continues to be suboptimal especially for unilateral small sized pathological conditions. Techniques such as laparoscopy have been utilized for visualization of buffalo ovaries however; their clinical use appears to be uncommon. The therapy of most ovarian pathologies except the functional disorders appears to be difficult. The prospects of surgical removal of ovaries in neoplastic ovarian pathologies are limited owing to the costs and loss of reproductive function under bilateral conditions. Oviductal pathologies in buffalo have been mentioned largely from abattoir studies and include salpingitis (0.2%–14.2%, hydrosalpinx (0.7%–14.2%, pyosalpinx (0.6%–11.9%, adhesions (1.5%–1.7%, congenital defects (0.2% and oviductal blockage (1.2%–37.8%. The diagnosis of most oviductal pathologies in buffalo appears to be difficult except under conditions of gross enlargement. Under situations of bilateral involvement the therapy of most oviductal pathologies currently seems impractical as the reattainment of fertility appears to be difficult.

  5. Using Generic Examples to Make Viable Arguments

    Science.gov (United States)

    Adams, Anne E.; Ely, Rob; Yopp, David

    2017-01-01

    The twenty-first century has seen an increased call to train students to craft mathematical arguments. The third of the Common Core's (CCSS) Standards for Mathematical Practice (SMP 3) (CCSSI 2010) calls for all mathematically proficient students to "construct viable arguments" to support the truth of their ideas and to "critique…

  6. Laminin Receptor-Avid Nanotherapeutic EGCg-AuNPs as a Potential Alternative Therapeutic Approach to Prevent Restenosis

    Science.gov (United States)

    Khoobchandani, Menka; Katti, Kavita; Maxwell, Adam; Fay, William P.; Katti, Kattesh V.

    2016-01-01

    In our efforts to develop new approaches to treat and prevent human vascular diseases, we report herein our results on the proliferation and migration of human smooth muscles cells (SMCs) and endothelial cells (ECs) using epigallocatechin-3-gallate conjugated gold nanoparticles (EGCg-AuNPs) as possible alternatives to drug coated stents. Detailed in vitro stability studies of EGCg-AuNPs in various biological fluids, affinity and selectivity towards SMCs and ECs have been investigated. The EGCg-AuNPs showed selective inhibitory efficacy toward the migration of SMCs. However, the endothelial cells remained unaffected under similar experimental conditions. The cellular internalization studies have indicated that EGCg-AuNPs internalize into the SMCs and ECs within short periods of time through laminin receptor mediated endocytosis mode. Favorable toxicity profiles and selective affinity toward SMCs and ECs suggest that EGCg-AuNPs may provide attractive alternatives to drug coated stents and therefore offer new therapeutic approaches in treating cardiovascular diseases. PMID:26938531

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

    Science.gov (United States)

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

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Laminin Receptor-Avid Nanotherapeutic EGCg-AuNPs as a Potential Alternative Therapeutic Approach to Prevent Restenosis

    Directory of Open Access Journals (Sweden)

    Menka Khoobchandani

    2016-03-01

    Full Text Available In our efforts to develop new approaches to treat and prevent human vascular diseases, we report herein our results on the proliferation and migration of human smooth muscles cells (SMCs and endothelial cells (ECs using epigallocatechin-3-gallate conjugated gold nanoparticles (EGCg-AuNPs as possible alternatives to drug coated stents. Detailed in vitro stability studies of EGCg-AuNPs in various biological fluids, affinity and selectivity towards SMCs and ECs have been investigated. The EGCg-AuNPs showed selective inhibitory efficacy toward the migration of SMCs. However, the endothelial cells remained unaffected under similar experimental conditions. The cellular internalization studies have indicated that EGCg-AuNPs internalize into the SMCs and ECs within short periods of time through laminin receptor mediated endocytosis mode. Favorable toxicity profiles and selective affinity toward SMCs and ECs suggest that EGCg-AuNPs may provide attractive alternatives to drug coated stents and therefore offer new therapeutic approaches in treating cardiovascular diseases.

  9. Incidence, clinical outcomes, and therapeutic approaches of capsule endoscopy-related adverse events in a large study population

    Directory of Open Access Journals (Sweden)

    Ignacio Fernández-Urien

    2015-12-01

    Full Text Available Introduction: Capsule endoscopy (CE has become a first-line tool for small bowel (SB examination. However, adverse events (AEs, such as CE retention or aspiration, may occur. The aims of this study were to evaluate incidence, clinical outcomes and therapeutic approaches of CE-related AEs in the largest series published to date. Methods: Data from 5428 procedures performed at 12 institutions between August 2001 and January 2012 were retrospectively analyzed. Baseline patient characteristics; procedure; type, localization and symptoms before/after AEs; previous patency tests performed; therapeutic management and patient's outcome were recorded. Results: The overall incidence of CE-related AEs was 1.9%: 2.0% for SB, 0.9% for esophageal and 0.5% for colon CE. The incidence of capsule retention was significantly higher than capsule aspiration (1.87% vs. 0.003%; p < 0.05, in patients suffering from inflammatory bowel disease (IBD than in obscure GI bleeding (OGIB (3.3% vs. 1.5%; p < 0.05 and in patients with the combination of nausea/vomiting, abdominal pain and distension. The SB was the most frequent localization of retention (88.2%. The use of patency tests -except for Patency© capsule- before CE was not a good predictor for AEs. Most of the patients with AEs developed no or mild symptoms (97% and were managed by non-surgical methods (64.4%. Conclusions: CE-related AEs are uncommon and difficult to predict by imagiological examinations. SB retention, that is usually asymptomatic, is the most frequent AE. In absence of symptoms, non-surgical management of CE-related AEs is recommended.

  10. [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.

  11. Therapeutical approaches to paroxysmal hemicrania, hemicrania continua and short lasting unilateral neuralgiform headache attacks: a critical appraisal.

    Science.gov (United States)

    Baraldi, Carlo; Pellesi, Lanfranco; Guerzoni, Simona; Cainazzo, Maria Michela; Pini, Luigi Alberto

    2017-12-01

    Hemicrania continua (HC), paroxysmal hemicrania (PH) and short lasting neuralgiform headache attacks (SUNCT and SUNA) are rare syndromes with a difficult therapeutic approach. The aim of this review is to summarize all articles dealing with treatments for HC, PH, SUNCT and SUNA, comparing them in terms of effectiveness and safety. A survey was performed using the pubmed database for documents published from the 1st January 1989 onwards. All types of articles were considered, those ones dealing with symptomatic cases and non-English written ones were excluded. Indomethacin is the best treatment both for HC and PH. For the acute treatment of HC, piroxicam and celecoxib have shown good results, whilst for the prolonged treatment celecoxib, topiramate and gabapentin are good options besides indomethacin. For PH the best drug besides indomethacin is piroxicam, both for acute and prolonged treatment. For SUNCT and SUNA the most effective treatments are intravenous or subcutaneous lidocaine for the acute treatment of active phases and lamotrigine for the their prevention. Other effective therapeutic options are intravenous steroids for acute treatment and topiramate for prolonged treatment. Non-pharmacological techniques have shown good results in SUNCT and SUNA but, since they have been tried on a small number of patients, the reliability of their efficacy is poor and their safety profile mostly unknown. Besides a great number of treatments tried, HC, PH, SUNCT and SUNA management remains difficult, according with their unknown pathogenesis and their rarity, which strongly limits the studies upon these conditions. Further studies are needed to better define the treatment of choice for these conditions.

  12. Acute myeloid leukemia in the elderly: a critical review of therapeutic approaches and appraisal of results of therapy.

    Science.gov (United States)

    Ferrara, F; Mirto, S; Zagonel, V; Pinto, A

    1998-04-01

    In the elderly, acute myeloid leukemia (AML) is characterized by a poorer prognosis than in younger patients, due to either host related factors (poor performance status, co-morbid diseases, organ function impairment) or the biology of leukemia itself (high incidence of adverse cytogenetic abnormalities, high frequency of preceding myelodysplastic syndromes, intrinsic resistance to cytotoxic drugs). Current therapeutic results are mostly unsatisfactory and studies reporting high rates of complete remission are probably influenced by selection biases as suggested by the low rate of elderly patients inclusion into cooperative trials. Availability of intensive support including hematopoietic growth factors could stimulate clinicians to manage an increasing number of elderly patients with AML with aggressive programs. However, chemotherapy in the elderly is difficult, costly and usually associated with high morbidity and mortality rate. Therefore, all efforts should be made to identify those subset of elderly patients in whom aggressive treatment may result in a true improvement of disease free and overall survival. The critical analysis of our five years experience, as reported here, seems to suggest that older AML patients displaying unfavourable prognostic factors at diagnosis (i.e., adverse karyotype and high serum LDH levels), but clinically eligible for intensive chemotherapy, do not actually benefit from an aggressive approach. A blind attempt to treat these patients aggressively may be associated with a life threatening toxicity not counterbalanced by an actual survival advantage. We suggest therefore that aggressive treatment should be reserved for elderly AML cases in whom the presence of good prognostic factors at diagnosis predicts that the loss of some patients due to toxicity may be balanced by the achievement of a substantial proportion of long term survivors. Finally, given the biological and clinical heterogeneity of elderly AML patients, a more

  13. The HIV protease inhibitor, nelfinavir, as a novel therapeutic approach for the treatment of refractory pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Meier-Stephenson V

    2017-05-01

    Full Text Available Vanessa Meier-Stephenson,1,2 Justin Riemer,1,2 Aru Narendran1–3 1Department of Oncology, Cumming School of Medicine, University of Calgary, 2Department of Pediatrics, Alberta Children’s Hospital, 3Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC Laboratory, Calgary, AB, Canada Purpose: Refractory pediatric leukemia remains one of the leading causes of death in children. Intensification of current chemotherapy regimens to improve the outcome in these children is often limited by the effects of drug resistance and cumulative toxicity. Hence, the search for newer agents and novel therapeutic approaches are urgently needed to formulate the next-generation early-phase clinical trials for these patients.Materials and methods: A comprehensive library of antimicrobials, including eight HIV protease inhibitors (nelfinavir [NFV], saquinavir, indinavir, ritonavir, amprenavir, atazanavir, lopinavir, and darunavir, was tested against a panel of pediatric leukemia cells by in vitro growth inhibition studies. Detailed target modulation studies were carried out by Western blot analyses. In addition, drug synergy experiments with conventional and novel antitumor agents were completed to identify effective treatment regimens for future clinical trials.Results: Several of the HIV protease inhibitors showed cytotoxicity at physiologically relevant concentrations (half-maximal inhibitory concentration values ranging from 1–24 µM. In particular, NFV was found to exhibit the most potent antileukemic properties across all cell lines tested. Mechanistic studies show that NFV leads to the induction of autophagy and apoptosis possibly through the induction of endoplasmic reticulum stress. Furthermore, interference with cell signaling pathways, including Akt and mTOR, was also noted. Finally, drug combination studies have identified agents with potential for synergy with NFV in its antileukemic activity. These include JQ1 (BET inhibitor

  14. Therapeutical approaches in melasma.

    Science.gov (United States)

    Prignano, Francesca; Ortonne, Jean-Paul; Buggiani, Gionata; Lotti, Torello

    2007-07-01

    Melasma (cloasma) is a typical hypermelanosis and a common dermatologic skin disease that involves sun-exposed areas of the skin. It mostly affects women of reproductive age. Solar and ultraviolet exposure are the most crucial etiologic factors. Pregnancy, certain endocrine disorders and hormonal treatments, cosmetics, phototoxic drugs, and antiseizure medications are well-known inducing and exacerbating factors. A classification of melasma is based on Wood's light examination, classifying it in four major clinical types and patterns: epidermal, dermal, mixed, and indeterminate. Different treatment options are currently available for melasma. The choice of proper treatment should take into account the type of melasma to be treated, the skin complexion of the patient, possible previous treatments, the expectations and compliance of the patient, and the season in which the treatment is started.

  15. Ferenczi's Revolutionary Therapeutic Approach.

    Science.gov (United States)

    Mucci, Clara

    2017-09-01

    Many of the revolutionary principles introduced by Ferenczi in his clinical practice have now been widely accepted especially in the field of trauma and trauma therapy. Examples of these innovative views include his emphasis on empathy as opposed to technical neutrality and his stress on the real conditions of child caring and family environmental deficits and on the consequences of interpersonal violence and abuse that lead to "identification with the aggressor" by the victim thereby resulting in the internalization of both aggressiveness and guilt (the split guilt of the abuser). The resulting "fragmentation" of the personality, which is now considered dissociation (instead of Freud's "repression"), is at the root of several severe disorders, characterized by distortion of reality, loss of touch with one's body and loss of trust in the other. Therefore "abreaction is not enough". A new, positive relational experience must be re-inscribed at the level of implicit memory.

  16. 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

  17. Monotone viable trajectories for functional differential inclusions

    Science.gov (United States)

    Haddad, Georges

    This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

  18. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments

    Science.gov (United States)

    Zhao, Min; Kong, Lei; Qu, Hong

    2014-01-01

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X chromosome. In addition, these genes were enriched in target lists of seven transcription factors and sixteen microRNAs. Using a network-based approach, we further reconstructed an IQ-related pathway from known human pathway interaction data. Based on this reconstructed pathway, we incorporated enriched drugs and described the importance of dopamine and norepinephrine systems in IQ-related biological process. These findings not only reveal several testable genes and processes related to IQ scores, but also have potential therapeutic implications for IQ-related mental disorders. PMID:24566931

  19. 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.

  20. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments.

    Science.gov (United States)

    Zhao, Min; Kong, Lei; Qu, Hong

    2014-02-25

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X chromosome. In addition, these genes were enriched in target lists of seven transcription factors and sixteen microRNAs. Using a network-based approach, we further reconstructed an IQ-related pathway from known human pathway interaction data. Based on this reconstructed pathway, we incorporated enriched drugs and described the importance of dopamine and norepinephrine systems in IQ-related biological process. These findings not only reveal several testable genes and processes related to IQ scores, but also have potential therapeutic implications for IQ-related mental disorders.

  1. 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

  2. Therapeutic approach to "downhill" esophageal varices bleeding due to superior vena cava syndrome in Behcet's disease: a case report

    Directory of Open Access Journals (Sweden)

    Haghighi Mahshid

    2006-12-01

    Full Text Available Abstract Background One of the rare presentations of superior vena cava syndrome is bleeding of "downhill" esophageal varices (DEV and different approaches have been used to control it. This is a case report whose DEV was eradicated by band ligation for the first time. Case presentation We report a 42-year-old man who is a known case of Behcet's disease. The patient's first presentation was superior vena cava syndrome due to thrombosis followed by bipolar ulcers and arthralgia. He received warfarin, prednisolone and azathioprine. The clinical course of the patient was complicated by one episode of hematemesis without abdominal pain when the patient's PT was in therapeutic range. After resuscitation and correction of PT with fresh frozen plasma transfusion, upper gastrointestinal endoscopy was done. Prominent varices were seen in the upper third of the esophagus, tapering to the middle part without acute bleeding. Stomach and duodenum were normal. Color ultrasonography evaluation of the portal, hepatic and splenic veins was negative for thrombosis. Band ligation was done and the patient's bleeding did not recur. Conclusion Band ligation is a safe and effective method for controlling DEV bleeding in patients with uncorrectable underlying disorders.

  3. Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach.

    Science.gov (United States)

    Habib, Abdul Musaweer; Islam, Md Saiful; Sohel, Md; Mazumder, Md Habibul Hasan; Sikder, Mohd Omar Faruk; Shahik, Shah Md

    2016-12-01

    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.

  4. 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.

  5. 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

  6. 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

  7. Selective Targeting of Interferon gamma to Stromal Fibroblasts and Pericytes as a Novel Therapeutic Approach to Inhibit Angiogenesis and Tumor Growth

    NARCIS (Netherlands)

    Bansal, Ruchi; Tomar, Tushar; Ostman, Arne; Poelstra, Klaas; Prakash, Jai

    2012-01-01

    New approaches to block the function of tumor stromal cells such as cancer-associated fibroblasts and pericytes is an emerging field in cancer therapeutics as these cells play a crucial role in promoting angiogenesis and tumor growth via paracrine signals. Because of immunomodulatory and other

  8. Air-spore in Cartagena, Spain: viable and non-viable sampling methods.

    Science.gov (United States)

    Elvira-Rendueles, Belen; Moreno, Jose; Garcia-Sanchez, Antonio; Vergara, Nuria; Martinez-Garcia, Maria Jose; Moreno-Grau, Stella

    2013-01-01

    In the presented study the airborne fungal spores of the semiarid city of Cartagena, Spain, are identified and quantified by means of viable or non-viable sampling methods. Airborne fungal samples were collected simultaneously using a filtration method and a pollen and particle sampler based on the Hirst methodology. This information is very useful for elucidating geographical patterns of hay fever and asthma. The qualitative results showed that when the non-viable methodology was employed, Cladosporium, Ustilago, and Alternaria were the most abundant spores identified in the atmosphere of Cartagena, while the viable methodology showed that the most abundant taxa were: Cladosporium, Penicillium, Aspergillus and Alternaria. The quantitative results of airborne fungal spores identified by the Hirst-type air sampler (non-viable method), showed that Deuteromycetes represented 74% of total annual spore counts, Cladosporium being the major component of the fungal spectrum (62.2%), followed by Alternaria (5.3%), and Stemphylium (1.3%). The Basidiomycetes group represented 18.9% of total annual spore counts, Ustilago (7.1%) being the most representative taxon of this group and the second most abundant spore type. Ascomycetes accounted for 6.9%, Nectria (2.3%) being the principal taxon. Oomycetes (0.2%) and Zygomycestes and Myxomycestes (0.06%) were scarce. The prevailing species define our bioaerosol as typical of dry air. The viable methodology was better at identifying small hyaline spores and allowed for the discrimination of the genus of some spore types. However, non-viable methods revealed the richness of fungal types present in the bioaerosol. Thus, the use of both methodologies provides a more comprehensive characterization of the spore profile.

  9. Parejas viables que perduran en el tiempo

    OpenAIRE

    Juan José Cuervo Rodríguez

    2013-01-01

    El presente artículo científico presenta resultados del proceso llevado a cabo en el proyecto de investigación docente "Mecanismos de autorregulación en parejas viables que perduran en el tiempo". Se soporta en una mirada compleja de la psicología basada en una epistemología de la construcción. En el ámbito metodológico, se inscribe en los estudios de terapia familiar desde una perspectiva de la comunicación humana como un todo integrado. Participaron nueve parejas. Los criterios de inclusión...

  10. Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'.

    Science.gov (United States)

    Akhtar, Naseem; Khan, Riaz A

    2016-10-01

    Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 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

  12. Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches

    National Research Council Canada - National Science Library

    deGoma, Emil M; deGoma, Rolando L; Rader, Daniel J

    2008-01-01

    A number of therapeutic strategies targeting high-density lipoprotein (HDL) cholesterol and reverse cholesterol transport are being developed to halt the progression of atherosclerosis or even induce regression...

  13. Psychosocial factors and therapeutic approaches in the context of sexual history taking in men: a study conducted among Swiss general practitioners and urologists.

    Science.gov (United States)

    Platano, Giacomo; Margraf, Jürgen; Alder, Judith; Bitzer, Johannes

    2008-11-01

    Male sexual dysfunction is a common medical condition, which is addressed mainly from a biomedical perspective by Swiss general practitioners (GPs) and urologists as the results of part I of our study showed. A psychosocial orientation in sexual history taking (SHT) leads to a truly patient-centered approach and is crucial for improving therapy decisions related to sexual dysfunction. To analyze to what extent Swiss GPs and urologists have a psychosocial orientation in SHT, and what therapeutic options they focus on when confronted with male sexual dysfunction. A semistructured interview was developed and used in face-to-face encounters with 25 GPs and 25 urologists. Content and frequency of interview responses. The GPs and urologists differed significantly from each other in 5 out of 22 psychosocial factors. Summarizing these psychosocial factors in four domains showed a difference between the GPs and urologists in only one domain. Both groups focus on an open conversation as their approach in SHT. No GP and only a minority of urologists based their diagnosis on criteria of the International Classification of Diseases (10th edition) (ICD-10) or Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). The GPs and urologists differed significantly from each other in 4 out of 16 combinations resulting from the given therapeutic options and form of sexual dysfunction. The urologists focus more strongly on medication as a therapeutic option. The results of part II additionally justify establishing guidelines and training resources related to SHT in Switzerland. Swiss physicians should be encouraged to apply a more psychosocial orientation in SHT. This will contribute to a better patient-centered approach with positive consequences on physicians' therapeutic decisions. Optimizing the approach in SHT and the choice of therapeutic options may better facilitate real sexual satisfaction for the patient and ultimately result in fewer health insurance

  14. Roots of success: cultivating viable community forestry

    Energy Technology Data Exchange (ETDEWEB)

    MacQueen, Duncan

    2009-05-15

    Is community forestry emerging from the shadows? The evidence shows that locally controlled enterprises can be economically viable, and often build on stronger social and environmental foundations than the big private-sector players. Certainly this is an industry in need of a shakeup. Many forests have become flashpoints where agro-industry, large-scale logging concerns and conservation interests clash, while forest-dependent communities are left out in the cold. Meanwhile, governments – driven by concerns over the climate impacts of deforestation – are having to gear up for legal, sustainable forestry production. Community forestry could be crucial to solving many of these challenges. By building on local core capabilities and developing strategic partnerships, they are forging key new business models that could transform the sector.

  15. Inkjet printing of viable human dental follicle stem cells

    Directory of Open Access Journals (Sweden)

    Mau Robert

    2015-09-01

    Full Text Available Inkjet printing technology has the potential to be used for seeding of viable cells for tissue engineering approaches. For this reason, a piezoelectrically actuated, drop-on-demand inkjet printing system was applied to deliver viable human dental follicle stem cells (hDFSC of sizes of about 15 μm up to 20 μm in diameter. The purpose of these investigations was to verify the stability of the printing process and to evaluate cell viability post printing. Using a Nanoplotter 2.1 (Gesim, Germany equipped with the piezoelectric printhead NanoTip HV (Gesim, Germany, a concentration of 6.6 ×106 cells ml−1 in DMEM with 10% fetal calf serum (FCS could be dispensed. The piezoelectric printhead has a nominal droplet volume of ~ 400 pl and was set to a voltage of 75 V and a pulse of 50 μs while dosing 50 000 droplets over a time of 100 seconds. The volume and trajectory of the droplet were checked by a stroboscope test right before and after the printing process. It was found that the droplet volume decreases significantly by 35% during printing process, while the trajectory of the droplets remains stable with only an insignificant number of degrees deviation from the vertical line. It is highly probable that some cell sedimentations or agglomerations affect the printing performance. The cell viability post printing was assessed by using the Trypan Blue dye exclusion test. The printing process was found to have no significant influence on cell survival. In conclusion, drop-on-demand inkjet printing can be a potent tool for the seeding of viable cells.

  16. 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

  17. An efficient liquid chromatography-high resolution mass spectrometry approach for the optimization of the metabolic stability of therapeutic peptides.

    Science.gov (United States)

    Esposito, Simone; Mele, Riccardo; Ingenito, Raffaele; Bianchi, Elisabetta; Bonelli, Fabio; Monteagudo, Edith; Orsatti, Laura

    2017-04-01

    In drug discovery, there is increasing interest in peptides as therapeutic agents due to several appealing characteristics that are typical of this class of compounds, including high target affinity, excellent selectivity, and low toxicity. However, peptides usually present also some challenging ADME (absorption, distribution, metabolism, and excretion) issues such as limited metabolic stability, poor oral bioavailability, and short half-lives. In this context, early preclinical in vitro studies such as plasma metabolic stability assays are crucial to improve developability of a peptidic drug. In order to speed up the optimization of peptide metabolic stability, a strategy was developed for the integrated semi-quantitative determination of metabolic stability of peptides and qualitative identification/structural elucidation of their metabolites in preclinical plasma metabolic stability studies using liquid chromatography-high-resolution Orbitrap™ mass spectrometry (LC-HRMS). Sample preparation was based on protein precipitation: experimental conditions were optimized after evaluating and comparing different organic solvents in order to obtain an adequate extraction of the parent peptides and their metabolites and to minimize matrix effect. Peptides and their metabolites were analyzed by reverse-phase liquid chromatography: a template gradient (total run time, 6 min) was created to allow retention and good peak shape for peptides of different polarity and isoelectric points. Three LC columns were selected to be systematically evaluated for each series of peptides. Targeted and untargeted HRMS data were simultaneously acquired in positive full scan + data-dependent MS/MS acquisition mode, and then processed to calculate plasma half-life and to identify the major cleavage sites, this latter by using the software Biopharma Finder™. Finally, as an example of the application of this workflow, a study that shows the plasma stability improvement of a series of

  18. Polymerase chain reaction-based discrimination of viable from non-viable Mycoplasma gallisepticum

    Directory of Open Access Journals (Sweden)

    Ching Giap Tan

    2014-02-01

    Full Text Available The present study was based on the reverse transcription polymerase chain reaction (RT-PCR of the 16S ribosomal nucleic acid (rRNA of Mycoplasma for detection of viable Mycoplasma gallisepticum. To determine the stability of M. gallisepticum 16S rRNA in vitro, three inactivation methods were used and the suspensions were stored at different temperatures. The 16S rRNA of M. gallisepticum was detected up to approximately 20–25 h at 37 °C, 22–25 h at 16 °C, and 23–27 h at 4 °C. The test, therefore, could detect viable or recently dead M. gallisepticum (< 20 h. The RT-PCR method was applied during an in vivo study of drug efficacy under experimental conditions, where commercial broiler-breeder eggs were inoculated with M. gallisepticum into the yolk. Hatched chicks that had been inoculated in ovo were treated with Macrolide 1. The method was then applied in a flock of day 0 chicks with naturally acquired vertical transmission of M. gallisepticum, treated with Macrolide 2. Swabs of the respiratory tract were obtained for PCR and RT-PCR evaluations to determine the viability of M. gallisepticum. This study proved that the combination of both PCR and RT-PCR enables detection and differentiation of viable from non-viable M. gallisepticum.

  19. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

    Directory of Open Access Journals (Sweden)

    Nelly Mezzaroba

    Full Text Available Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  20. Mammalian cell display technology coupling with AID induced SHM in vitro: an ideal approach to the production of therapeutic antibodies.

    Science.gov (United States)

    Qin, Chang-Fei; Li, Guan-Cheng

    2014-12-01

    Traditional antibody production technology within non-mammalian cell expression systems has shown many unsatisfactory properties for the development of therapeutic antibodies. Nevertheless, mammalian cell display technology reaps the benefits of producing full-length all human antibodies. Together with the developed cytidine deaminase induced in vitro somatic hypermutation technology, mammalian cell display technology provides the opportunity to produce high affinity antibodies that might be ideal for therapeutic application. This review was concentrated on the development of the mammalian cell display technology as well as the activation-induced cytidine deaminase induced in vitro somatic hypermutation technology and their applications for the production of therapeutic antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Illness, disease, sickness : Clinical factors, concepts of pain and sick leave patterns among immigrants in primary health care. Effects of different therapeutic approaches

    OpenAIRE

    Löfvander, Monica

    1997-01-01

    Illness, disease, sickness. Clinical factors, concepts of pain and sick leave patterns amongimmigrants in primary health care. Effects of different therapeutic approaches Monica Löfvander The outer framework for this thesis is the high rate of disability pensions amongsome immigrant groups in Sweden. The general aim for the research has been to understandthe phenomena of illness, disease and sickness certification in immigrants from aprimary care perspective and ...

  2. Connexin-Based Therapeutics and Tissue Engineering Approaches to the Amelioration of Chronic Pancreatitis and Type I Diabetes: Construction and Characterization of a Novel Prevascularized Bioartificial Pancreas

    Directory of Open Access Journals (Sweden)

    J. Matthew Rhett

    2016-01-01

    Full Text Available Total pancreatectomy and islet autotransplantation is a cutting-edge technique to treat chronic pancreatitis and postoperative diabetes. A major obstacle has been low islet cell survival due largely to the innate inflammatory response. Connexin43 (Cx43 channels play a key role in early inflammation and have proven to be viable therapeutic targets. Even if cell death due to early inflammation is avoided, insufficient vascularization is a primary obstacle to maintaining the viability of implanted cells. We have invented technologies targeting the inflammatory response and poor vascularization: a Cx43 mimetic peptide that inhibits inflammation and a novel prevascularized tissue engineered construct. We combined these technologies with isolated islets to create a prevascularized bioartificial pancreas that is resistant to the innate inflammatory response. Immunoconfocal microscopy showed that constructs containing islets express insulin and possess a vascular network similar to constructs without islets. Glucose stimulated islet-containing constructs displayed reduced insulin secretion compared to islets alone. However, labeling for insulin post-glucose stimulation revealed that the constructs expressed abundant levels of insulin. This discrepancy was found to be due to the expression of insulin degrading enzyme. These results suggest that the prevascularized bioartificial pancreas is potentially a tool for improving long-term islet cell survival in vivo.

  3. Increase in Endoscopic and Laparoscopic Surgery Regarding the Therapeutic Approach of Gastric Cancer Detected by Cancer Screening in Saga Prefecture, Japan.

    Science.gov (United States)

    Yamaguchi, Shunsuke; Sakata, Yasuhisa; Iwakiri, Ryuichi; Hara, Megumi; Akutagawa, Kayo; Shimoda, Ryo; Yamaguchi, Daisuke; Hidaka, Hidenori; Sakata, Hiroyuki; Fujimoto, Kazuma; Mizuguchi, Masanobu; Shimoda, Yuichiro; Irie, Hiroyuki; Noshiro, Hirokazu

    2016-01-01

    Objective Despite recent advances in endoscopic treatment and laparoscopic surgery for gastric cancers, an increase in the uptake of these therapeutic approaches has not yet been fully demonstrated. Therefore, the present study aimed to investigate the change in therapeutic approaches regarding the treatment of gastric cancers detected by cancer screening in Saga Prefecture, Japan between April 2002 and March 2011. Methods Gastric cancer screening by X-ray was performed on 311,074 subjects between April 2002 and March 2011. In total, 534 patients were thereafter diagnosed with gastric cancer. Eighteen subjects were excluded because precise details of their treatment were not available. To evaluate the changes in the therapeutic approach, the observation period was divided into three 3-year intervals: Period I: April 2002 to March 2005; Period II: April 2005 to March 2008; Period III: April 2008 to March 2011. Results The use of open laparotomy for the treatment of gastric cancer decreased, and laparoscopic surgery and endoscopic treatment increased markedly in a time-dependent manner. A 2.5-fold increase in endoscopic treatment, and a 18.4-fold increase in laparoscopic surgery were observed in Period III compared with Period I (after adjusting for age and tumor characteristics). Conclusion Endoscopic treatment and laparoscopic surgery for gastric cancer increased during the investigation period (2002-2011), although the tumor characteristics of the gastric cancers detected through cancer screening in Saga Prefecture, Japan did not show any changes.

  4. The Conceptual Mechanism for Viable Organizational Learning Based on Complex System Theory and the Viable System Model

    Science.gov (United States)

    Sung, Dia; You, Yeongmahn; Song, Ji Hoon

    2008-01-01

    The purpose of this research is to explore the possibility of viable learning organizations based on identifying viable organizational learning mechanisms. Two theoretical foundations, complex system theory and viable system theory, have been integrated to provide the rationale for building the sustainable organizational learning mechanism. The…

  5. Deletion of ultraconserved elements yields viable mice

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.

    2007-07-15

    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  6. Is Greenberg's "Macro-Carib" viable?

    Directory of Open Access Journals (Sweden)

    Spike Gildea

    Full Text Available In his landmark work Language in the Americas, Greenberg (1987 proposed that Macro-Carib was one of the major low-level stocks of South America, which together with Macro-Panoan and Macro-Ge-Bororo were claimed to comprise the putative Ge-Pano-Carib Phylum. His Macro-Carib includes the isolates Andoke and Kukura, and the Witotoan, Peba-Yaguan, and Cariban families. Greenberg's primary evidence came from person-marking paradigms in individual languages, plus scattered words from individual languages collected into 79 Macro-Carib 'etymologies' and another 64 Amerind 'etymologies'. The goal of this paper is to re-evaluate Greenberg's Macro-Carib claim in the light of the much more extensive and reliable language data that has become available largely since 1987. Based on full person-marking paradigms for Proto-Cariban, Yagua, Bora and Andoke, we conclude that Greenberg's morphological claims are unfounded. For our lexical comparison, we created lexical lists for Proto-Cariban, Proto-Witotoan, Yagua and Andoke, for both Greenberg's 143 putative etymologies and for the Swadesh 100 list. From both lists, a total of 23 potential cognates were found, but no consonantal correspondences were repeated even once. We conclude that our greatly expanded and improved database does not provide sufficient evidence to convince the skeptic that the Macro-Carib hypothesis is viable

  7. Heel melanoma: the final result of wrong diagnostic and therapeutic approach in another bulgarian patient. First documented case from the board of the “adcrstr-association for dermatohistopathologic control, reevaluation and subsequent therapeutic recomme.

    Science.gov (United States)

    Chokoeva, A A; Tchernev, G; Gianfaldoni, S; Patterson, J W; Wollina, U; Lotti, T

    2015-01-01

    recommendations of the AJCC. Unfortunately disease progression was observed with loco-regional lymph node involvement. Systemic therapy with interferon was planned. The incorrect therapeutic approach in this patient, as well as the several subsequent misdiagnoses that were made in the leading pathology departments of the capital, undoubtedly helped lead to the creation of a national board with international participation in order to minimize errors in the diagnostic and therapeutic approach in dermatology, surgery and histopathology. The already-created Association for Dermatohistopathologic Control, Reevaluation and Subsequent Therapeutic Recommendations-ADCRSTR, aims to take control of histopathological preparations with wrong diagnoses and subsequent therapy in patients with cutaneous tumors, as well as their documentation. Another task of the Institution is to focus on the preservation and protection of the rights and interests of affected patients.

  8. 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.

  9. Dual abrogation of MNK and mTOR: a novel therapeutic approach for the treatment of aggressive cancers.

    Science.gov (United States)

    Lineham, Ella; Spencer, John; Morley, Simon J

    2017-09-01

    Targeting the translational machinery has emerged as a promising therapeutic option for cancer treatment. Cancer cells require elevated protein synthesis and exhibit augmented activity to meet the increased metabolic demand. Eukaryotic translation initiation factor 4E is necessary for mRNA translation, its availability and phosphorylation are regulated by the PI3K/AKT/mTOR and MNK1/2 pathways. The phosphorylated form of eIF4E drives the expression of oncogenic proteins including those involved in metastasis. In this article, we will review the role of eIF4E in cancer, its regulation and discuss the benefit of dual inhibition of upstream pathways. The discernible interplay between the MNK and mTOR signaling pathways provides a novel therapeutic opportunity to target aggressive migratory cancers through the development of hybrid molecules.

  10. Herbal therapeutics that block the oncogenic kinase PAK1: a practical approach towards PAK1-dependent diseases and longevity.

    Science.gov (United States)

    Maruta, Hiroshi

    2014-05-01

    Over 35 years research on PAKs, RAC/CDC42(p21)-activated kinases, comes of age, and in particular PAK1 has been well known to be responsible for a variety of diseases such as cancer (mainly solid tumors), Alzheimer's disease, acquired immune deficiency syndrome and other viral/bacterial infections, inflammatory diseases (asthma and arthritis), diabetes (type 2), neurofibromatosis, tuberous sclerosis, epilepsy, depression, schizophrenia, learning disability, autism, etc. Although several distinct synthetic PAK1-blockers have been recently developed, no FDA-approved PAK1 blockers are available on the market as yet. Thus, patients suffering from these PAK1-dependent diseases have to rely on solely a variety of herbal therapeutics such as propolis and curcumin that block PAK1 without affecting normal cell growth. Furthermore, several recent studies revealed that some of these herbal therapeutics significantly extend the lifespan of nematodes (C. elegans) and fruit flies (Drosophila), and PAK1-deficient worm lives longer than the wild type. Here, I outline mainly pathological phenotypes of hyper-activated PAK1 and a list of herbal therapeutics that block PAK1, but cause no side (harmful) effect on healthy people or animals. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Parejas viables que perduran en el tiempo

    Directory of Open Access Journals (Sweden)

    Juan José Cuervo Rodríguez

    2013-01-01

    Full Text Available El presente artículo científico presenta resultados del proceso llevado a cabo en el proyecto de investigación docente "Mecanismos de autorregulación en parejas viables que perduran en el tiempo". Se soporta en una mirada compleja de la psicología basada en una epistemología de la construcción. En el ámbito metodológico, se inscribe en los estudios de terapia familiar desde una perspectiva de la comunicación humana como un todo integrado. Participaron nueve parejas. Los criterios de inclusión fueron: cinco o más años de convivencia, participación voluntaria, no presentar (ni haber presentado problemáticas especiales que ameriten intervención psicoterapéutica y la obtención de un porcentaje significativo en el uso de estrategias de comunicación asertiva en la resolución de conflictos. El método general utilizado fue el análisis de la comunicación en tarea de conversación. Los principales hallazgos señalan una estrecha relación entre el contexto de desarrollo de las parejas, la emergencia de códigos comunicacionales propios y la posibilidad de perdurar en el tiempo; también, se resalta el tipo de comunicación asertiva o constructiva, la construcción de valores como el respeto y la aceptación de las diferencias, y el deseo por vivir y construir bienestar común, como elementos constitutivos de su identidad como pareja.

  12. The Use of a Therapeutic Jurisprudence Approach to the Teaching and Learning of Law to a New Generation of Law Students in South Africa

    Directory of Open Access Journals (Sweden)

    E Fourie

    2012-03-01

    Full Text Available In rapidly changing social, economic and intellectual environments it is imperative that teaching and learning should be transformed from being primarily concerned with the transmission of knowledge (learning about to being primarily concerned with the practices of a knowledge domain (learning to be. Law lecturers are faced with a new generation of law students, many of whom may be the first in their families to enter university, and one of the important challenges that we face, when educating law students, is how to enable these students to take their place in a very important profession. To meet this challenge it is necessary to instill skills that will be beneficial to the profession, future clients and the community as a whole. We at the University of Johannesburg are endeavouring to do so through embracing a therapeutic jurisprudence approach that focuses on the well-being of the student, the client and the community. The integration of therapeutic jurisprudence throughout the law student's studies, starting with orientation and continuing through to the final-year clinical experience, will enhance the therapeutic outcomes for all of the parties involved. A therapeutic jurisprudence approach, combined with appropriate teaching and learning methods, will enhance the student's interpersonal skills and writing and reading skills. The teaching methods invoked include role-play to transform formal knowledge into living knowledge, thereby stimulating students' natural practical curiosity and creating a learning environment that supports collaboration and encourages students to act purposefully in such an environment. This article discusses the teaching of first-generation students and how to overcome the existing social, cultural, economic and linguistic barriers by using a therapeutic jurisprudence approach, while upholding the values that should guide legal practice, such as integrity and respect for diversity and human dignity. The

  13. Is telomerase a viable target in cancer?

    Science.gov (United States)

    Buseman, C.M.; Wright, W.E.; Shay, J.W.

    2012-01-01

    The ideal cancer treatment would specifically target cancer cells yet have minimal or no adverse effects on normal somatic cells. Telomerase, the ribonucleoprotein reverse transcriptase that maintains the ends of human chromosome, is an attractive cancer therapeutic target for exactly this reason [1]. Telomerase is expressed in more than 85% of cancer cells, making it a nearly universal cancer marker, while the majority of normal somatic cells are telomerase negative. Telomerase activity confers limitless replicative potential to cancer cells, a hallmark of cancer which must be attained for the continued growth that characterizes almost all advanced neoplasms [2]. In this review we will summarize the role of telomeres and telomerase in cancer cells, and how properties of telomerase are being exploited to create targeted cancer therapies including telomerase inhibitors, telomerase-targeted immunotherapies and telomerase-driven virotherapies. A frank and balanced assessment of the current state of telomerase inhibitors with caveats and potential limitations will be included. PMID:21802433

  14. Combining ethidium monoazide treatment with real-time PCR selectively quantifies viable Batrachochytrium dendrobatidis cells.

    Science.gov (United States)

    Blooi, Mark; Martel, An; Vercammen, Francis; Pasmans, Frank

    2013-02-01

    Detection of the lethal amphibian fungus Batrachochytrium dendrobatidis relies on PCR-based techniques. Although highly accurate and sensitive, these methods fail to distinguish between viable and dead cells. In this study a novel approach combining the DNA intercalating dye ethidium monoazide (EMA) and real-time PCR is presented that allows quantification of viable B. dendrobatidis cells without the need for culturing. The developed method is able to suppress real-time PCR signals of heat-killed B. dendrobatidis zoospores by 99.9 % and is able to discriminate viable from heat-killed B. dendrobatidis zoospores in mixed samples. Furthermore, the novel approach was applied to assess the antifungal activity of the veterinary antiseptic F10(®) Antiseptic Solution. This disinfectant killed B. dendrobatidis zoospores effectively within 1 min at concentrations as low as 1:6400. Copyright © 2013 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  15. 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 Modalities INTRODUCTION Lung cancer is the most prevalent cancer worldwide and the leading cause of cancer-related mortality in both men...11C-PD153035. Chin Med J (Engl) 120:960–964 12. Memon AA, Jakobsen S, Dagnaes-Hansen F, Sorensen BS, Keiding S, Nexo E (2009) Positron emission...for a long period of time. However, you should wait 2 hours before holding an infant or getting close to a pregnant woman to avoid exposing them to

  16. The Role of Histone Deacetylases in Neurodegenerative Diseases and Small-Molecule Inhibitors as a Potential Therapeutic Approach

    Science.gov (United States)

    Bürli, Roland W.; Thomas, Elizabeth; Beaumont, Vahri

    Neurodegenerative disorders are devastating for patients and their social environment. Their etiology is poorly understood and complex. As a result, there is clearly an urgent need for therapeutic agents that slow down disease progress and alleviate symptoms. In this respect, interference with expression and function of multiple gene products at the epigenetic level has offered much promise, and histone deacetylases play a crucial role in these processes. This review presents an overview of the biological pathways in which these enzymes are involved and illustrates the complex network of proteins that governs their activity. An overview of small molecules that interfere with histone deacetylase function is provided.

  17. Investigation of molecular mechanism of recognition between citral and MARK4: A newer therapeutic approach to attenuate cancer cell progression.

    Science.gov (United States)

    Naz, Farha; Khan, Faez Iqbal; Mohammad, Taj; Khan, Parvez; Manzoor, Saaliqa; Hasan, Gulam Mustafa; Lobb, Kevin A; Luqman, Suaib; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2018-02-01

    Microtubule affinity regulating kinase 4 (MARK4) is a member of AMP-activated protein kinase, found to be involved in apoptosis, inflammation and many other regulatory pathways. Since, its aberrant expression is directly associated with the cell cycle and thus cancer. Therefore, MARK4 is being considered as a potential drug target for cancer therapy. Here, we investigated the mechanism of inhibition of MARK4 activity by citral. Docking studies suggested that citral effectively binds to the active site cavity, and complex is stabilized by several interactions. We further performed molecular dynamics simulation of MARK4-citral complex under explicit water condition for 100ns and observed that binding of citral to MARK4 was quite stable. Fluorescence binding studies suggested that citral strongly binds to MARK4 and thereby inhibits its enzyme activity which was measured by the kinase inhibition assay. We further performed MTT assay and observed that citral inhibits proliferation of breast cancer cell line MCF-7. This work provides a newer insight into the use of citral as novel cancer therapeutics through the MARK4 inhibition. Results may be employed to design novel therapeutic molecule using citral as a scaffold for MARK4 inhibition to fight related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. [Chemistry approach for therapeutic education of children with hemophilia and their parents: Representation of complex phenomena related to treatment].

    Science.gov (United States)

    Novais, T; Meunier, S; Trossaërt, M; Salmon, D; Chamouard, V

    2016-08-01

    The therapeutic management of hemophilia is based on replacement therapy by clotting factor concentrates and may require several injections per week. In teenagers, non-compliance with treatment may be responsible for major orthopedic complications. The aim of this study was to develop and assess an educational intervention for children with hemophilia and their parents, thus illustrating the complex phenomena related to treatment and its adhesion. The construction of the educational workshop and tools was based on the concrete, visual, and playful representation of the following concepts: pathophysiology, the replacement therapy's mechanism of action, drug elimination requiring repeated administrations, and inhibitor development. The procedure was then assessed by a sample of children and parents using a questionnaire. A 60- to 90-min workshop was developed. The different tools used to illustrate the severity of the disease, the effect of the injected drug, drug elimination, and the inhibitor effect were: a blue-to-transparent colorimetric scale in bottles, a weekly timeline, Muppets, and a slow redox reaction. Five children and eight parents assessed this educational intervention with a rating of 3.75/4 (±0.10) and 3.60/4 (±0.45), respectively. The intervention developed could be transposed to other chronic diseases with similar therapeutic characteristics (including replacement mechanism of action and pharmacokinetics). Understanding the transmitted pharmacological concepts in a playful way is a major challenge to encourage treatment adhesion during adolescence. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Profiling Total Viable Bacteria in a Hemodialysis Water Treatment System.

    Science.gov (United States)

    Chen, Lihua; Zhu, Xuan; Zhang, Menglu; Wang, Yuxin; Lv, Tianyu; Zhang, Shenghua; Yu, Xin

    2017-05-28

    Culture-dependent methods, such as heterotrophic plate counting (HPC), are usually applied to evaluate the bacteriological quality of hemodialysis water. However, these methods cannot detect the uncultured or viable but non-culturable (VBNC) bacteria, both of which may be quantitatively predominant throughout the hemodialysis water treatment system. Therefore, propidium monoazide (PMA)-qPCR associated with HPC was used together to profile the distribution of the total viable bacteria in such a system. Moreover, high-throughput sequencing of 16S rRNA gene amplicons was utilized to analyze the microbial community structure and diversity. The HPC results indicated that the total bacterial counts conformed to the standards, yet the bacteria amounts were abruptly enhanced after carbon filter treatment. Nevertheless, the bacterial counts detected by PMA-qPCR, with the highest levels of 2.14 × 10 7 copies/100 ml in softener water, were much higher than the corresponding HPC results, which demonstrated the occurrence of numerous uncultured or VBNC bacteria among the entire system before reverse osmosis (RO). In addition, the microbial community structure was very different and the diversity was enhanced after the carbon filter. Although the diversity was minimized after RO treatment, pathogens such as Escherichia could still be detected in the RO effluent. In general, both the amounts of bacteria and the complexity of microbial community in the hemodialysis water treatment system revealed by molecular approaches were much higher than by traditional method. These results suggested the higher health risk potential for hemodialysis patients from the up-to-standard water. The treatment process could also be optimized, based on the results of this study.

  2. PMA-Linked Fluorescence for Rapid Detection of Viable Bacterial Endospores

    Science.gov (United States)

    LaDuc, Myron T.; Venkateswaran, Kasthuri; Mohapatra, Bidyut

    2012-01-01

    The most common approach for assessing the abundance of viable bacterial endospores is the culture-based plating method. However, culture-based approaches are heavily biased and oftentimes incompatible with upstream sample processing strategies, which make viable cells/spores uncultivable. This shortcoming highlights the need for rapid molecular diagnostic tools to assess more accurately the abundance of viable spacecraft-associated microbiota, perhaps most importantly bacterial endospores. Propidium monoazide (PMA) has received a great deal of attention due to its ability to differentiate live, viable bacterial cells from dead ones. PMA gains access to the DNA of dead cells through compromised membranes. Once inside the cell, it intercalates and eventually covalently bonds with the double-helix structures upon photoactivation with visible light. The covalently bound DNA is significantly altered, and unavailable to downstream molecular-based manipulations and analyses. Microbiological samples can be treated with appropriate concentrations of PMA and exposed to visible light prior to undergoing total genomic DNA extraction, resulting in an extract comprised solely of DNA arising from viable cells. This ability to extract DNA selectively from living cells is extremely powerful, and bears great relevance to many microbiological arenas.

  3. Awareness Levels about Breast Cancer Risk Factors, Early Warning Signs, and Screening and Therapeutic Approaches among Iranian Adult Women: A large Population Based Study Using Latent Class Analysis

    Directory of Open Access Journals (Sweden)

    Mahdi Tazhibi

    2014-01-01

    Full Text Available Background and Objective. Breast cancer (BC continues to be a major cause of morbidity and mortality among women throughout the world and in Iran. Lack of awareness and early detection program in developing country is a main reason for escalating the mortality. The present research was conducted to assess the Iranian women’s level of knowledge about breast cancer risk factors, early warning signs, and therapeutic and screening approaches, and their correlated determinants. Methods. In a cross-sectional study, 2250 women before participating at a community based screening and public educational program in an institute of cancer research in Isfahan, Iran, in 2012 were investigated using a self-administered questionnaire about risk factors, early warning signs, and therapeutic and screening approaches of BC. Latent class regression as a comprehensive statistical method was used for evaluating the level of knowledge and its correlated determinants. Results. Only 33.2%, 31.9%, 26.7%, and 35.8% of study participants had high awareness levels about screening approaches, risk factors, early warning signs and therapeutic modalities of breast cancer, respectively, and majority had poor to moderate knowledge levels. Most effective predictors of high level of awareness were higher educational qualifications, attending in screening and public educational programs, personal problem, and family history of BC, respectively. Conclusion. Results of current study indicated that the levels of awareness among study population about key elements of BC are low. These findings reenforce the continuing need for more BC education through conducting public and professional programs that are intended to raise awareness among younger, single women and those with low educational attainments and without family history.

  4. Tenoscopy of the navicular bursa: a new therapeutic approach for horses affected by "palmar pain syndrome." Endoscopic technique review and personal experiences.

    Science.gov (United States)

    Scandella, M; Lazzaretti, S S; De Zani, D; Cassano, M; Zani, D D; Ravasio, G; Gualtieri, M

    2010-06-01

    Tenoscopy of the navicular bursa has been recently introduced as a diagnostic and therapeutic treatment in cases of palmar foot pain syndrome. A deep digital flexor tendon transthecal approach was suggested in 1999, and the endoscopic technique has been reviewed. Smith and coworkers have recently reported good and promising results. An anatomic cadaver limb study was performed, and the endoscopic technique was evaluated. Subsequently, a 14-year-old Argentine mare, affected by palmar foot pain syndrome, was treated. Clinical data, MRI and endoscopic findings, and a 6-month follow-up evaluation are reported.

  5. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue.

    Science.gov (United States)

    Schwartz, Joseph; Winters, Jeffrey L; Padmanabhan, Anand; Balogun, Rasheed A; Delaney, Meghan; Linenberger, Michael L; Szczepiorkowski, Zbigniew M; Williams, Mark E; Wu, Yanyun; Shaz, Beth H

    2013-07-01

    The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence-based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the "level of evidence" criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. Copyright © 2013 Wiley Periodicals, Inc.

  6. Restoration of Wild-Type Activity to Mutant p53 in Prostate Cancer: A Novel Therapeutic Approach

    National Research Council Canada - National Science Library

    Manfredi, James

    2006-01-01

    A summary is presented of research performed during the first year of a project to determine feasibility of approaches to restore wild-type transcriptional activity on mutant p53 proteins found in human prostate tumors...

  7. Restoration of Wild-Type Activity to Mutant p53 in Prostate Cancer: A Novel Therapeutic Approach

    National Research Council Canada - National Science Library

    Manfredi, James J

    2008-01-01

    A summary is presented of research performed during three years of a project to determine feasibility of approaches to restore wild-type transcriptional activity on mutant p53 proteins found in human prostate tumors...

  8. The integrated approach of yoga: a therapeutic tool for mentally retarded children: a one-year controlled study.

    Science.gov (United States)

    Uma, K; Nagendra, H R; Nagarathna, R; Vaidehi, S; Seethalakshmi, R

    1989-10-01

    Ninety children with mental retardation of mild, moderate and severe degree were selected from four special schools in Bangalore, India. Forty-five children underwent yogic training for one academic year (5 h in every week) with an integrated set of yogic practices, including breathing exercises and pranayama, sithilikarana vyayama (loosening exercises), suryanamaskar, yogasanas and meditation. They were compared before and after yogic training with a control group of 45 mentally retarded children matched for chronological age, sex, IQ, socio-economic status and socio environmental background who were not exposed to yoga training but continued their usual school routine during that period. There was highly significant improvement in the IQ and social adaptation parameters in the yoga group as compared to the control group. This study shows the efficacy of yoga as an effective therapeutic tool in the management of mentally retarded children.

  9. Magnetic thermotherapy of breast tumors: an experimental therapeutic approach; Magnetische Thermotherapie von Tumoren der Brust: ein experimenteller Therapieansatz

    Energy Technology Data Exchange (ETDEWEB)

    Hilger, I.; Kaiser, W.A. [Inst. fuer Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Univ. Jena (Germany); Andrae, W.; Hergt, R.; Hiergeist, R. [Inst. fuer Physikalische Hochtechnologie e.V., Jena (Germany)

    2005-04-01

    The therapeutic strategy for breast cancer is changing, especially for early tumor stages with good prognosis. One potential minimally invasive therapy modality consists in the accumulation of a well-tolerated magnetic material (iron oxides, particularly magnetite) in the target tissue. By applying an alternating magnetic field, energy is selectively absorbed and induces harmful heating of the tumor. The present review deals with the essential conditions and parameters as studied in vitro and in vivo in animal experiments. Extrapolations to the clinical situation are discussed, in particular, the heating potential of the magnetic material, the selection of the magnetic field parameters, the occurrence of eddy currents, the generation of localized heating spots and the expected temperature rises and their effects on the tumor area. (orig.)

  10. Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

    Science.gov (United States)

    Zhou, Ming-Da; Hao, Sijie; Williams, Anthony J.; Harouaka, Ramdane A.; Schrand, Brett; Rawal, Siddarth; Ao, Zheng; Brennaman, Randall; Gilboa, Eli; Lu, Bo; Wang, Shuwen; Zhu, Jiyue; Datar, Ram; Cote, Richard; Tai, Yu-Chong; Zheng, Si-Yang

    2014-12-01

    The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.

  11. Asouzu's Complementary Ontology as a Foundation for a Viable ...

    African Journals Online (AJOL)

    This paper on “Asouzu's Complementary Ontology as a foundation for a viable Ethic of the Environment”, posits that an ethic of the environment can be seen as viable if it considers the whole of reality as ontologically relevant. This point of view would free environmental ethics of anthropocentric bias and its attendant ...

  12. A 2-step optical coherence tomography guided therapeutic approach to acute myocardial infarction secondary to stent thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Bogale, Nigussie, E-mail: nigussie.bogale@lyse.net [Vancouver General Hospital, Division of Cardiology University of British Columbia, Vancouver, BC (Canada); Stavanger University Hospital, Department of Cardiology, Stavanger (Norway); Lempereur, Mathieu; Fung, Anthony Y. [Vancouver General Hospital, Division of Cardiology University of British Columbia, Vancouver, BC (Canada)

    2016-07-15

    Myocardial infarction secondary to stent thrombosis has high mortality and recurrence rate. Emergency PCI has high risk of no-reflow. We used a 2-step approach of early recanalization with minimal mechanical intervention followed by delayed PCI 1–2 days later guided by Optical Coherence Tomography (OCT). From October 2011 to December 2013, we treated 5 patients with this approach. Time from early recanalization to the delayed definitive PCI was 1 day (median, range 1–3 days). All the OCT images were diagnostic with a clear view of the underlying structures. Summary: A 2-step approach to treat stent thrombosis appears beneficial with low incidence of peri-procedural thrombosis or no-reflow phenomena during the second step, and superb OCT imaging.

  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. Therapeutic applications of carbon nanotubes: opportunities and challenges.

    Science.gov (United States)

    Rogers-Nieman, Gabrielle M; Dinu, Cerasela Zoica

    2014-01-01

    Based on their physicochemical properties that allow efficient functionalization with biomolecules and cellular membrane translocation, as well as on their applications in Raman and near-infrared fluorescence imaging, carbon nanotubes (CNTs) have been proposed as viable candidates for developing therapeutic platforms that ensure targeting of tumor cells without affecting healthy cells. This article reviews the research on toxicological effects of CNTs on host cells, as well as their pharmacological profiles on cancer cells. The potential impact of this approach is discussed along with some potential pitfalls that will need to be overcome when therapeutic implementation CNTs are considered. For further resources related to this article, please visit the WIREs website. The authors declare no competing financial interest. © 2014 Wiley Periodicals, Inc.

  15. Issues of organizational cybernetics and viability beyond Beer's viable systems model

    Science.gov (United States)

    Nechansky, Helmut

    2013-11-01

    The paper starts summarizing the claims of Beer's viable systems model to identify five issues any viable organizations has to deal with in an unequivocal hierarchical structure of five interrelated systems. Then the evidence is introduced for additional issues and related viable structures of organizations, which deviate from Beer's model. These issues are: (1) the establishment and (2) evolution of an organization; (3) systems for independent top-down control (like "Six Sigma"); (4) systems for independent bottom-up correction of performance problems (like "Kaizen"), both working outside a hierarchical structure; (5) pull production systems ("Just in Time") and (6) systems for checks and balances of top-level power (like boards and shareholder meetings). Based on that an evolutionary approach to organizational cybernetics is outlined, addressing the establishment of organizations and possible courses of developments, including recent developments in quality and production engineering, as well as problems of setting and changing goal values determining organizational policies.

  16. Endometrial stromal sarcomas frequently express epidermal growth factor receptor (EGFR, HER-1): potential basis for a new therapeutic approach.

    Science.gov (United States)

    Moinfar, Farid; Gogg-Kamerer, Margit; Sommersacher, Andrea; Regitnig, Peter; Man, Yan Gao; Zatloukal, Kurt; Denk, Helmut; Tavassoli, Fattaneh A

    2005-04-01

    Endometrial stromal sarcomas are rare malignant mesenchymal uterine tumors. The expressions of different epidermal growth factor receptors such as EGFR (HER-1), HER-2, HER-3, and HER-4 have not yet been examined in these tumors. Twenty-three cases of endometrial sarcomas consisting of 20 low-grade endometrial stromal sarcomas and 3 undifferentiated endometrial sarcomas were examined immunohistochemically for EGFR (HER-1), HER-2, HER-3, and HER-4. EGFR (HER-1) was positive in 17 of 23 (74%) cases. While the three undifferentiated endometrial sarcomas were positive for EGFR, 14 of 20 (70%) low-grade endometrial stromal sarcomas showed positive reactions for EGFR. All examined cases were negative for HER-2, HER-3, and HER-4. This study is the first to show common expression of EGFR (HER-1) in endometrial stromal sarcomas. This finding may provide the basis for a new therapeutic strategy using monoclonal antibodies against EGFR (such as cetuximab) or small molecule inhibitors of EGFR (such as gefitinib) in patients with endometrial sarcomas.

  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. Separation of viable and non-viable tomato (Solanum lycopersicum L.) seeds using single seed near-infrared spectroscopy

    DEFF Research Database (Denmark)

    Shrestha, Santosh; Deleuran, Lise Christina; Gislum, René

    2017-01-01

    -viable tomato seeds of two cultivars using chemometrics. The data exploration were performed by principal component analysis (PCA). Subsequently, viable and non-viable seeds were classified by partial least squares-discriminant analysis (PLS-DA) and interval PLS-DA (iPLS-DA). The indication of clustering...... of viable and non-viable seeds were observed in the PCA of each cultivar and the pooled samples. However, the PCA did not exhibit a pattern of separation among the early, normal and late germinated tomato seeds. The NIR spectral regions of 1160–1170, 1383–1397, 1647–1666, 1860–1884 and 1915–1940 nm were...... identified as important for classification of viable and non-viable tomato seeds by iPLS-DA. The sensitivity i.e. ability to correctly identify the positive samples and specificity i.e. ability to reject the negative samples of the (iPLS-DA) model on identified spectral regions for prediction of viable...

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

    Science.gov (United States)

    2009-03-01

    Hong WK, Wistuba II, Lotan R. Immunohistochemical ardó-Vila M, Zurita AJ, Giordano RJ, Sun J, Rangel R, Guzman -Rojas L, Anobom CD, Valente olella...Cure Rate Model with an Unknown Threshold LUIS E. NIETO-BARAJAS Department of Statistics, ITAM GUOSHENG YIN Department of Biostatistics, M.D. Anderson...a unified approach. Can. J. Statist. 33, 559–570. Received September 2006, in final form October 2007 Luis E. Nieto-Barajas, Department of Statistics

  20. 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.

  1. 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.

  2. 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

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

    Science.gov (United States)

    Krylov, Victor; Shaburova, Olga; Krylov, Sergey; Pleteneva, Elena

    2012-01-01

    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. PMID:23344559

  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. Massive Ethylene Glycol Ingestion Treated with Fomepizole Alone—A Viable Therapeutic Option

    National Research Council Canada - National Science Library

    Buchanan, Jennie A; Alhelail, Mohammed; Cetaruk, Edward W; Schaeffer, Tammi H; Palmer, Robert B; Kulig, Ken; Brent, Jeffrey

    2010-01-01

    Fomepizole is used to treat and prevent toxicity from ethylene glycol poisoning. Treatment with fomepizole without hemodialysis in massive ethylene glycol ingestion has been rarely reported in the literature...

  6. Texture analysis of cardiac cine magnetic resonance imaging to detect non-viable segments in patients with chronic myocardial infarction.

    Science.gov (United States)

    Larroza, Andrés; López-Lereu, María P; Monmeneu, José V; Gavara, Jose; Chorro, Francisco J; Bodí, Vicente; Moratal, David

    2018-02-01

    To investigate the ability of texture analysis to differentiate between infarcted non-viable, viable, and remote segments on cardiac cine magnetic resonance imaging (MRI). This retrospective study included 50 patients suffering chronic myocardial infarction. The data was randomly split into training (30 patients) and testing (20 patients) sets. The left ventricular myocardium was segmented according to the 17-segment model in both cine and late gadolinium enhancement (LGE) MRI. Infarcted myocardium regions were identified on LGE in short-axis views. Non-viable segments were identified as those showing LGE ≥ 50%, and viable segments those showing 0 cine images. A support vector machine (SVM) classifier was trained with different combination of texture features to obtain a model that provided optimal classification performance. The best classification on testing set was achieved with local binary patterns features using a 2D + t approach, in which the features are computed by including information of the time dimension available in cine sequences. The best overall area under the receiver operating characteristic curve (AUC) were: 0.849, sensitivity of 92% to detect non-viable segments, 72% to detect viable segments, and 85% to detect remote segments. Non-viable segments can be detected on cine MRI using texture analysis and this may be used as hypothesis for future research aiming to detect the infarcted myocardium by means of a gadolinium-free approach. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Is the step-wise tiered approach for ERA of pharmaceuticals useful for the assessment of cancer therapeutic drugs present in marine environment?

    Science.gov (United States)

    Aguirre-Martínez, G V; Okello, C; Salamanca, M J; Garrido, C; Del Valls, T A; Martín-Díaz, M L

    2016-01-01

    Methotrexate (MTX) and tamoxifen (TMX) cancer therapeutic drugs have been detected within the aquatic environment. Nevertheless, MTX and TMX research is essentially bio-medically orientated, with few studies addressing the question of its toxicity in fresh water organisms, and none to its' effect in the marine environment. To the authors' knowledge, Environmental Risk Assessments (ERA) for pharmaceuticals has mainly been designed for freshwater and terrestrial environments (European Medicines Agency-EMEA guideline, 2006). Therefore, the purpose of this research was (1) to assess effect of MTX and TMX in marine organism using the EMEA guideline, (2) to develop an ERA methodology for marine environment, and (3) to evaluate the suitability of including a biomarker approach in Phase III. To reach these aims, a risk assessment of MTX and TMX was performed following EMEA guideline, including a 2-tier approach during Phase III, applying lysosomal membrane stability (LMS) as a screening biomarker in tier-1 and a battery of biochemical biomarkers in tier-2. Results from Phase II indicated that MTX was not toxic for bacteria, microalgae and sea urchin at the concentrations tested, thus no further assessment was required, while TMX indicated a possible risk. Therefore, Phase III was performed for only TMX. Ruditapes philippinarum were exposed during 14 days to TMX (0.1, 1, 10, 50 μg L(-1)). At the end of the experiment, clams exposed to environmental concentration indicated significant changes in LMS compared to the control (ppharmaceuticals in marine environment which includes sensitive endpoints. The inadequacy of current EMEA guideline to predict chemotherapy agents toxicity in Phase II was displayed whilst the usefulness of other tests were demonstrated. The 2-tier approach, applied in Phase III, appears to be suitable for an ERA of cancer therapeutic drugs in the marine environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Keeping checkpoint/restart viable for exascale systems.

    Energy Technology Data Exchange (ETDEWEB)

    Riesen, Rolf E.; Bridges, Patrick G. (IBM Research, Ireland, Mulhuddart, Dublin); Stearley, Jon R.; Laros, James H., III; Oldfield, Ron A.; Arnold, Dorian (University of New Mexico, Albuquerque, NM); Pedretti, Kevin Thomas Tauke; Ferreira, Kurt Brian; Brightwell, Ronald Brian

    2011-09-01

    Next-generation exascale systems, those capable of performing a quintillion (10{sup 18}) operations per second, are expected to be delivered in the next 8-10 years. These systems, which will be 1,000 times faster than current systems, will be of unprecedented scale. As these systems continue to grow in size, faults will become increasingly common, even over the course of small calculations. Therefore, issues such as fault tolerance and reliability will limit application scalability. Current techniques to ensure progress across faults like checkpoint/restart, the dominant fault tolerance mechanism for the last 25 years, are increasingly problematic at the scales of future systems due to their excessive overheads. In this work, we evaluate a number of techniques to decrease the overhead of checkpoint/restart and keep this method viable for future exascale systems. More specifically, this work evaluates state-machine replication to dramatically increase the checkpoint interval (the time between successive checkpoint) and hash-based, probabilistic incremental checkpointing using graphics processing units to decrease the checkpoint commit time (the time to save one checkpoint). Using a combination of empirical analysis, modeling, and simulation, we study the costs and benefits of these approaches on a wide range of parameters. These results, which cover of number of high-performance computing capability workloads, different failure distributions, hardware mean time to failures, and I/O bandwidths, show the potential benefits of these techniques for meeting the reliability demands of future exascale platforms.

  9. Surgical mistake causing an high recto-vaginal fistula. A case report with combined surgical and endoscopic approach: therapeutic considerations

    Science.gov (United States)

    2013-01-01

    Background Rectovaginal fistulas (RVFs) have multiple causes, size and location on which the surgical treatment depends. Description The Authors consider different approaches to RVFs and describe a clinical case of recurrent high RVF. Conclusions Most RVFs can be successfully repaired, although many interventions may be necessary. A colostomy with delayed repair may improve RVFs outcome. Moreover, several authors indicate Mucosal Advancement Flap and Babcock-Bacon technique as the treatments of choice respectively for low and high RVFs (complex and recurrent) and emphasize the placement of endoscopic prothesis in cases of difficult healing of the anastomosis. PMID:24266908

  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. 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

  12. 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% O2 + 90% N2). 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 [KITT] HFHSu sham, 2.56 ± 0.41% glucose/min; KITT 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

  13. 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.

  14. 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.

  15. Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs

    Directory of Open Access Journals (Sweden)

    Cardelli Pierluigi

    2011-09-01

    Full Text Available Abstract Background Cancer is one of the most difficult current health challenges, being responsible for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach, and the prevailing orientation calls for the administration of the maximum tolerated dose; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. Electrochemotherapy (ECT is a tumor treatment that combines the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses. In this article we evaluate the capability of ECT to allow the use of cisplatin despite its high toxicity in a spontaneous feline model of soft tissue sarcoma. Methods A cohort of sixty-four cats with incompletely excised sarcomas were treated with cisplatin-based adjuvant ECT and monitored for side effects. Their response was compared to that of fourteen cats treated with surgery alone. Results The toxicities were minimal and mostly treated symptomatically. ECT resulted in increased local control (median not reached at the time of writing with a mean time to recurrence of 666 days versus 180 of controls. Conclusions We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols.

  16. Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches.

    Science.gov (United States)

    de Bartolomeis, Andrea; Latte, Gianmarco; Tomasetti, Carmine; Iasevoli, Felice

    2014-02-01

    Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic synapses, and made by scaffolding proteins, receptors, and effector proteins; it is considered a structural and functional crossroad where multiple neurotransmitter systems converge, including the dopaminergic, serotonergic, and glutamatergic ones, which are all implicated in the pathophysiology of psychosis. Decreased PSD-95 protein levels have been reported in postmortem brains of schizophrenia patients. Variants of Homer1, a key PSD protein for glutamate signaling, have been associated with schizophrenia symptoms severity and therapeutic response. Mutations in Shank gene have been recognized in autism spectrum disorder patients, as well as reported to be associated to behaviors reminiscent of schizophrenia symptoms when expressed in genetically engineered mice. Here, we provide a critical appraisal of PSD proteins role in the pathophysiology of schizophrenia and autism spectrum disorders. Then, we discuss how antipsychotics may affect PSD proteins in brain regions relevant to psychosis pathophysiology, possibly by controlling synaptic plasticity and dendritic spine rearrangements through the modulation of glutamate-related targets. We finally provide a framework that may explain how PSD proteins might be useful candidates to develop new therapeutic approaches for schizophrenia and related disorders in which there is a need for new biological treatments, especially against some symptom domains, such as negative symptoms, that are poorly affected by current antipsychotics.

  17. Nano-particles for therapeutical purposes: an innovative approach for the radiotherapy of cancer;Les nanoparticules therapeutiques: une voie novatrice pour la radiotherapie appliquee a la cancerologie

    Energy Technology Data Exchange (ETDEWEB)

    Borghi, E.; Said, P.; Pottier, A.; Levy, L. [Nanobiotix, 75 - Paris (France)

    2010-02-15

    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

  18. Loco-regional cancer drug therapy: present approaches and rapidly reversible hydrophobization (RRH) of therapeutic agents as the future direction.

    Science.gov (United States)

    Budker, Vladimir G; Monahan, Sean D; Subbotin, Vladimir M

    2014-12-01

    Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Viable Cell Culture Banking for Biodiversity Characterization and Conservation.

    Science.gov (United States)

    Ryder, Oliver A; Onuma, Manabu

    2018-02-15

    Because living cells can be saved for indefinite periods, unprecedented opportunities for characterizing, cataloging, and conserving biological diversity have emerged as advanced cellular and genetic technologies portend new options for preventing species extinction. Crucial to realizing the potential impacts of stem cells and assisted reproductive technologies on biodiversity conservation is the cryobanking of viable cell cultures from diverse species, especially those identified as vulnerable to extinction in the near future. The advent of in vitro cell culture and cryobanking is reviewed here in the context of biodiversity collections of viable cell cultures that represent the progress and limitations of current efforts. The prospects for incorporating collections of frozen viable cell cultures into efforts to characterize the genetic changes that have produced the diversity of species on Earth and contribute to new initiatives in conservation argue strongly for a global network of facilities for establishing and cryobanking collections of viable cells.

  20. Pregnancy-Associated Plasma Protein-A and its Role in Cardiovascular Disease. Biology, Experimental/Clinical Evidences and Potential Therapeutic Approaches.

    Science.gov (United States)

    Ziviello, Francesca; Conte, Stefano; Cimmino, Giovanni; Sasso, Ferdinando Carlo; Trimarco, Bruno; Cirillo, Plinio

    2017-01-01

    Pregnancy-Associated Plasma Protein-A (PAPP-A) is a zinc-binding metalloproteinase protein produced by placental syncytio-trophoblasts and secreted into the maternal circulation where its concentration progressively increases until term. In recent years, PAPP-A has been studied for its potential involvement in cardiovascular (CV) disease. However, all those studies did not provide a clear view to identify the pathophysiological links between PAPP-A plasma levels and the occurrence of CV events. In this review, starting from a complete description of PAPP-A structure and biology, we present an updated overview of experimental as well as clinical evidence on the role of this metalloproteinase in CV disease. Finally, we discuss possible therapeutic approaches to antagonize its potential detrimental CV effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. 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.

  2. Derrame pleural complicado na criança: Abordagem terapêutica Complicated pleural effusion in children: Therapeutical approach

    Directory of Open Access Journals (Sweden)

    Sara Martins

    2007-01-01

    Full Text Available A abordagem do derrame pleural parapneumónico complicado, em idade pediátrica, permanece controversa. As opções terapêuticas incluem antibioticoterapia e drenagem pleural contínua, instilação intrapleural de fibrinolíticos, videotoracoscopia e toracotomia com descorticação. O objectivo deste estudo foi rever, avaliar e actualizar a abordagem ao derrame pleural complicado. Procedeu-se à revisão retrospectiva dos processos clínicos das crianças internadas na UPP por derrame pleural complicado entre 1992 e 2003. Foram incluídos 25 doentes, com idade média (±DP: 37,4 (± 37,0 meses, sendo 15/25 (60% do sexo masculino. A identificação do agente foi possível em 17/25 (68% casos [S. Aureus 6/17 (35%, St. pneumoniae 5/17 (29%], no líquido pleural em 16/17 (94% casos. Todos os doentes realizaram toracocentese e antibioticoterapia sistémica. A drenagem pleural contínua foi instituída em 22/25 (88% casos com duração média (±DP: 14,2 (± 7,8 dias; em 1 caso houve instilação de fibrinolíticos intrapleurais e em 11/25 (44% realizou-se toracotomia com descorticação. Um doente foi submetido a videotoracoscopia primária. A duração média de internamento (±DP foi de 30,4 (± 15,1 dias e não ocorreram óbitos. A experiência do centro é determinante na abordagem escolhida e na rapidez de actuação. Provavelmente ambas influenciam o prognóstico imediato.Pediatric management of complicated pleural effusion (CPE remains controversial. Different approaches include antibiotics and chest tube drainage alone or the use of fibrinolitics, videothorascoscopy (VTC and surgical decortication through thoracotomy. The aim of the present study was to review, evaluate and update technical approach to CPE. We retrospectively reviewed the clinical files of children admitted to the Pediatric Respiratory Ward between 1992 and 2003 with the diagnosis of CPE. Twenty-five patients were included [15 male (60%]. Mean (±SD age was 37,4 (±37

  3. 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.

  4. 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.

  5. Profile of a Serial Killer: Cellular and Molecular Approaches to Study Individual Cytotoxic T-Cells following Therapeutic Vaccination

    Directory of Open Access Journals (Sweden)

    Emanuela M. Iancu

    2011-01-01

    Full Text Available T-cell vaccination may prevent or treat cancer and infectious diseases, but further progress is required to increase clinical efficacy. Step-by-step improvements of T-cell vaccination in phase I/II clinical studies combined with very detailed analysis of T-cell responses at the single cell level are the strategy of choice for the identification of the most promising vaccine candidates for testing in subsequent large-scale phase III clinical trials. Major aims are to fully identify the most efficient T-cells in anticancer therapy, to characterize their TCRs, and to pinpoint the mechanisms of T-cell recruitment and function in well-defined clinical situations. Here we discuss novel strategies for the assessment of human T-cell responses, revealing in part unprecedented insight into T-cell biology and novel structural principles that govern TCR-pMHC recognition. Together, the described approaches advance our knowledge of T-cell mediated-protection from human diseases.

  6. Profile of a serial killer: cellular and molecular approaches to study individual cytotoxic T-cells following therapeutic vaccination.

    Science.gov (United States)

    Iancu, Emanuela M; Baumgaertner, Petra; Wieckowski, Sébastien; Speiser, Daniel E; Rufer, Nathalie

    2011-01-01

    T-cell vaccination may prevent or treat cancer and infectious diseases, but further progress is required to increase clinical efficacy. Step-by-step improvements of T-cell vaccination in phase I/II clinical studies combined with very detailed analysis of T-cell responses at the single cell level are the strategy of choice for the identification of the most promising vaccine candidates for testing in subsequent large-scale phase III clinical trials. Major aims are to fully identify the most efficient T-cells in anticancer therapy, to characterize their TCRs, and to pinpoint the mechanisms of T-cell recruitment and function in well-defined clinical situations. Here we discuss novel strategies for the assessment of human T-cell responses, revealing in part unprecedented insight into T-cell biology and novel structural principles that govern TCR-pMHC recognition. Together, the described approaches advance our knowledge of T-cell mediated-protection from human diseases.

  7. Radiofrequency Ablation in the Management of Advanced Stage Thymomas: A Case Report on a Novel Multidisciplinary Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Panagiotis Paliogiannis

    2014-01-01

    Full Text Available We describe in this report a case of successful radiofrequency ablation of an unresectable stage III-type B3 thymoma, and we discuss the role of this novel approach in the management of patients with advanced stage thymoma. The patient, a 59-year-old Caucasian male underwent neoadjuvant chemotherapy with only a slight reduction of the mass. Subsequently, an explorative sternotomy and debulking were performed; before closing the thorax, radiofrequency ablation of the residual tumor was carried out and a partial necrosis of the mass was achieved. A further percutaneous radiofrequency ablation was performed subsequently, obtaining complete necrosis of the lesion. Successively, the patient underwent adjuvant radiotherapy. As a result of this multidisciplinary treatment, complete and stable response was obtained. It is hard to say which of the single treatments had the major impact on cure; nevertheless, the results obtained suggest that radiofrequency ablation must be taken into account for the treatment of advanced stage thymomas, and its effectiveness must be further assessed in future studies.

  8. 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

    2017-12-22

    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

  9. Adapting drug approval pathways for bacteriophage-based therapeutics

    Directory of Open Access Journals (Sweden)

    Callum Cooper

    2016-08-01

    Full Text Available The global rise of multi-drug resistant bacteria has resulted in the notion that an antibiotic apocalypse is fast approaching. This has led to a number of well publicized calls for global funding initiatives to develop new antibacterial agents. The long clinical history of phage therapy in Eastern Europe, combined with more recent in vitro and in vivo success, demonstrates the potential for whole phage or phage based antibacterial agents. To date, no whole phage or phage derived products are approved for human therapeutic use in the EU or USA. There are at least three reasons for this: (i phages possess different biological, physical and pharmacological properties compared to conventional antibiotics. Phages need to replicate in order to achieve a viable antibacterial effect, resulting in complex pharmacodynamics / pharmacokinetics. (ii The specificity of individual phages requires multiple phages to treat single species infections, often as part of complex cocktails. (iii The current approval process for antibacterial agents has evolved with the development of chemically based drugs at its core, and is not suitable for phages. Due to similarities with conventional antibiotics, phage derived products such as endolysins are suitable for approval under current processes as biological therapeutic proteins. These criteria render the approval of phages for clinical use theoretically possible but not economically viable. In this review, pitfalls of the current approval process will be discussed for whole phage and phage derived products, in addition to the utilization of alternative approval pathways including adaptive licensing and Right to try legislation.

  10. Assessment of diagnostic and therapeutic approaches of Helicobacter pylori-associated iron deficiency and anemia in children with dyspeptic symptoms.

    Science.gov (United States)

    El-Aziz Awad, Mohiee El-Deen; Amin, Saleh Mohamed; Abdou, Saied Mohamed

    2014-12-01

    This study assessed the diagnostic approaches of Helicobacter pylori (IP)-associated iron deficiency (ID) and anemia (IDA) in children with dyspeptic symptoms and evaluated the effect of simultaneous anti-H. pylori (anti-HIP) therapy and oral iron in comparison with each of anti? HP therapy and oral iron therapy alone, on iron status as assessed by serum soluble transferrin receptor (sTfR) level. Two hundreds children with dyspeptic symptoms were subjected to clinical evaluation, stool examination, CBC, biochemical assays for serum iron parameters and measurements of serum IgG antibodies to HP and serum sTfR level by ELISA. Sixty children were found to have HP. associated ID or IDA and were randomly divided into 3 groups (20 children each). GA received 2-week anti-HP therapy plus 90-day oral iron, and GB received 2-week anti-HP therapy alone whereas group C received 90-day oral iron alone. Re-evaluation of the 3 groups was performed after 3 months of treatment initiation by repeat CBC and serum sTfR level. Children (45%) were HP-seropositive. The mean values of serum sTfR were significantly higher in HP-positive group and in HP-positive children with IDA than in HP-negative group and in HP-negative children with IDA although no significant differences were noted in hematologic variables and iron parameters between the corresponding groups and children. As regard treatment groups, there were significant improvements in the mean values of indices of IDA status (HIb, MCH, MCV, sTfR) and ID status (sTtRi) at 3 months of treatment initiation compared with their baseline values after. anti-HP triple therapy either with oral iron or without oral iron whereas the control children who were treated with oral iron alone showed insignificant changes despite oral iron administration. The improvements in these parameters were significantly greater in groups of children who received anti-HP therapy either combined with iron or alone, where compared with those who did not receive

  11. Navigating the Future of Cardiovascular Drug Development-Leveraging Novel Approaches to Drive Innovation and Drug Discovery: Summary of Findings from the Novel Cardiovascular Therapeutics Conference.

    Science.gov (United States)

    Povsic, Thomas J; Scott, Rob; Mahaffey, Kenneth W; Blaustein, Robert; Edelberg, Jay M; Lefkowitz, Martin P; Solomon, Scott D; Fox, Jonathan C; Healy, Kevin E; Khakoo, Aarif Y; Losordo, Douglas W; Malik, Fady I; Monia, Brett P; Montgomery, Rusty L; Riesmeyer, Jeffrey; Schwartz, Gregory G; Zelenkofske, Steven L; Wu, Joseph C; Wasserman, Scott M; Roe, Matthew T

    2017-08-01

    The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era. Participants then reviewed the use of innovative approaches being explored to facilitate rapid and more cost-efficient evaluations of drug candidates in a short timeframe. We summarize observations gleaned from this summit and offer insight into future cardiovascular drug development. The rapid development in genetic and high-throughput drug evaluation technologies, coupled with new approaches to rapidly evaluate potential cardiovascular therapies with in vitro techniques, offer opportunities to identify new drug targets for cardiovascular disease, study new therapies with better efficiency and higher throughput in the preclinical setting, and more rapidly bring the most promising therapies to human testing. However, there must be a critical interface between industry and academia to guide the future of cardiovascular drug development. The shared interest among academic institutions and pharmaceutical companies in developing promising therapies to address unmet clinical needs for patients with cardiovascular disease underlies and guides innovation and discovery platforms that are significantly altering the landscape of cardiovascular drug development.

  12. Therapeutical approach to rheumatoid arthritis

    OpenAIRE

    Paraskevi Gourni; Evaggelos Giavasopoulos

    2008-01-01

    Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of the synovial joints, and loss of the function leading to disability. The ultimate goal in managing RA is to prevent joint damage and to maintain functional ability. Although, οver the past decade, major advances have been made in our understanding of the factors that are crucial in regulating this disease, still the managment of the disease remains difficult.Aim : Τhe aim of the present study was the evaluation ...

  13. [Therapeutic approach to postoperative anemia].

    Science.gov (United States)

    Bisbe Vives, E; Moltó, L

    2015-06-01

    Postoperative anemia is a common finding in patients who undergo major surgery, and it can affect early rehabilitation and the return to daily activities. Allogeneic blood transfusion is still the most widely used method for restoring hemoglobin levels rapidly and effectively. However, the potential risks of transfusions have led to the review of this practice and to a search for alternative measures for treating postoperative anemia. The early administration of intravenous iron appears to improve the evolution of postoperative hemoglobin levels and reduce allogeneic transfusions, especially in patients with significant iron deficiency or anemia. What is not clear is whether this treatment heavily influences rehabilitation and quality of life. There is a lack of well-designed, sufficiently large, randomized prospective studies to determine whether postoperative or perioperative intravenous iron treatment, with or without recombinant erythropoietin, has a role in the recovery from postoperative anemia, in reducing transfusions and morbidity rates and in improving exercise capacity and quality of life. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    hemophilia and many storage disor- ders), cell-tissue-organ transplantation ... young women suffering from PKU give birth to very severely ... Hemophilia A. 4. Factor IX. Hemophilia B. 5. Erythropoietin. Anemia. 6. Alpha Galactosidase. Fabry disease. In mild conditions, provision of enzyme co-factors or activators, mostly vita-.

  15. Therapeutic approach to electrolyte emergencies.

    Science.gov (United States)

    Schaer, Michael

    2008-05-01

    Hypokalemia, hyperkalemia, hyponatremia, hypernatremia, hypocalcemia, and hypercalcemia are commonly seen in emergency medicine. Severe abnormalities in any of these electrolytes can cause potentially life-threatening consequences to the patient. It is essential that the clinician understand and correct (if possible) the underlying cause of each disorder and recognize the importance of the rates of correction, especially with serum sodium disorders. The recommended doses in this article might have to be adjusted to the individual patient, and these modifications must be adjusted again to the pathophysiology of the primary underlying disorder.

  16. Experimental design for the optimization of propidium monoazide treatment to quantify viable and non-viable bacteria in piggery effluents.

    Science.gov (United States)

    Desneux, Jérémy; Chemaly, Marianne; Pourcher, Anne-Marie

    2015-08-16

    Distinguishing between viable and dead bacteria in animal and urban effluents is a major challenge. Among existing methods, propidium monoazide (PMA)-qPCR is a promising way to quantify viable cells. However, its efficiency depends on the composition of the effluent, particularly on total suspended solids (TSS)) and on methodological parameters. The aim of this study was evaluate the influence of three methodological factors (concentration of PMA, incubation time and photoactivation time) on the efficiency of PMA-qPCR to quantify viable and dead cells of Listeria monocytogenes used as a microorganism model, in two piggery effluents (manure and lagoon effluent containing 20 and 0.4 TSS g.kg(-1), respectively). An experimental design strategy (Doehlert design and desirability function) was used to identify the experimental conditions to achieve optimal PMA-qPCR results. The quantification of viable cells of L. monocytogenes was mainly influenced by the concentration of PMA in the manure and by the duration of photoactivation in the lagoon effluent. Optimal values differed with the matrix: 55 μM PMA, 5 min incubation and 56 min photoactivation for manure and 20 μM PMA, 20 min incubation and 30 min photoactivation for lagoon effluent. Applied to five manure and four lagoon samples, these conditions resulted in satisfactory quantification of viable and dead cells. PMA-qPCR can be used on undiluted turbid effluent with high levels of TSS, provided preliminary tests are performed to identify the optimal conditions.

  17. 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.

  18. Role of chymase in the local renin-angiotensin system in keloids: inhibition of chymase may be an effective therapeutic approach to treat keloids

    Science.gov (United States)

    Wang, Ru; Chen, Junjie; Zhang, Zhenyu; Cen, Ying

    2015-01-01

    Background Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. Recently, it was reported that chymase induced a profibrotic response via transforming growth factor-β1 (TGF-β1)/Smad activation in keloid fibroblasts (KFs). However, the role of chymase in the local renin-angiotensin system (RAS) in keloids has not been elucidated. This study aims to determine whether chymase plays an important role in the local RAS in keloids. Methods We compared the expression and activity of chymase in keloids and normal skin tissues using Western blotting and radioimmunoassay, and studied the expression of TGF-β1, interleukin-1β, collagen I, hydroxyproline, and angiotensin II in KFs after chymase and inhibitors’ treatment. Results The results revealed an increased activity of chymase in keloid tissues, and that chymase enhanced the expression of angiotensin II, collagen I, TGF-β1, and interleukin-1β in KFs. Blockade of the chymase pathway involved in the local RAS lowered the expression of these signaling factors. Conclusion This research suggests that inhibition of chymase might be an effective therapeutic approach to improve the clinical treatment of keloids. PMID:26357464

  19. The Importance of Extensive Intraoperative Peritoneal Lavage as a Promising Method in Patients with Gastric Cancer Showing Positive Peritoneal Cytology Without Overt Peritoneal Metastasis and Other Therapeutic Approaches.

    Science.gov (United States)

    Ilhan, Enver; Alemdar, Ali; Ureyen, Orhan; Bas, Koray

    2017-10-01

    Peritoneal invasion is more common and has a worse prognosis in gastric cancer than most of other intestinal cancers. Advanced gastric cancers have a poor course in terms of the development of peritoneal carcinomatosis and prognosis, even if the curative resection has been performed. Patients usually die within the first 2 years of the postoperative period mainly due to peritoneal metastasis. It is, therefore, essential to eradicate intraperitoneal free cancer cells to prevent peritoneal recurrences. A standard therapy has not been developed yet for patients with gastric cancer with a positive peritoneal cytology or a gross peritoneal metastasis. Curative resection following neoadjuvant chemotherapy, postoperative oral S-1 chemotherapy, intraoperative intraperitoneal chemotherapy (IPC), and extensive intraoperative peritoneal lavage (EIPL)-IPC are recommended as therapeutic approaches. Although there is a limited number of studies on EIPL, which is a promising and exciting method in this patient population, unexpected results of survival have been demonstrated. We consider that the results of ongoing and further studies would lead to an extensive use of EIPL, which is a simple and easy method which can be applied anywhere and anytime, in patients with advanced gastic cancer and/or peritoneal cytology positive but peritoneal metastasis negative (CY+/P0) gastric cancer.

  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. 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.

  2. 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.

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

    Science.gov (United States)

    Pétré, Benoit; Gagnayre, Remi; De Andrade, Vincent; Ziegler, Olivier; Guillaume, Michèle

    2017-01-01

    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 behavior. Best TPE practices should encourage personal work on this, opening professionals to the social, experiential and emotional aspects of managing chronic illness.

  4. 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.

  5. 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.

  6. The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer.

    Science.gov (United States)

    Rebello, Richard J; Kusnadi, Eric; Cameron, Donald P; Pearson, Helen B; Lesmana, Analia; Devlin, Jennifer R; Drygin, Denis; Clark, Ashlee K; Porter, Laura; Pedersen, John; Sandhu, Shahneen; Risbridger, Gail P; Pearson, Richard B; Hannan, Ross D; Furic, Luc

    2016-11-15

    The MYC oncogene is frequently overexpressed in prostate cancer. Upregulation of ribosome biogenesis and function is characteristic of MYC-driven tumors. In addition, PIM kinases activate MYC signaling and mRNA translation in prostate cancer and cooperate with MYC to accelerate tumorigenesis. Here, we investigate the efficacy of a single and dual approach targeting ribosome biogenesis and function to treat prostate cancer. The inhibition of ribosomal RNA (rRNA) synthesis with CX-5461, a potent, selective, and orally bioavailable inhibitor of RNA polymerase I (Pol I) transcription, has been successfully exploited therapeutically but only in models of hematologic malignancy. CX-5461 and CX-6258, a pan-PIM kinase inhibitor, were tested alone and in combination in prostate cancer cell lines, in Hi-MYC- and PTEN-deficient mouse models and in patient-derived xenografts (PDX) of metastatic tissue obtained from a patient with castration-resistant prostate cancer. CX-5461 inhibited anchorage-independent growth and induced cell-cycle arrest in prostate cancer cell lines at nanomolar concentrations. Oral administration of 50 mg/kg CX-5461 induced TP53 expression and activity and reduced proliferation (MKI67) and invasion (loss of ductal actin) in Hi-MYC tumors, but not in PTEN-null (low MYC) tumors. While 100 mg/kg CX-6258 showed limited effect alone, its combination with CX-5461 further suppressed proliferation and dramatically reduced large invasive lesions in both models. This rational combination strategy significantly inhibited proliferation and induced cell death in PDX of prostate cancer. Our results demonstrate preclinical efficacy of targeting the ribosome at multiple levels and provide a new approach for the treatment of prostate cancer. Clin Cancer Res; 22(22); 5539-52. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. The search for viable local government system in Nigeria: an ...

    African Journals Online (AJOL)

    The history of the Nigerian local government system has been one long episode of trails and errors aimed at achieving viable local government institution without much success. Local government in the country began its long series of reforms from the colonial period when the colonial government attempted to ...

  8. Detection of viable toxigenic Vibrio cholerae and virulent Shigella ...

    African Journals Online (AJOL)

    A rapid and sensitive assay was developed for the detection of low numbers of viable Vibrio cholerae and Shigella spp. cells in environmental and drinking water samples. Water samples were filtered, and the filters were enriched in a non-selective medium. The enrichment cultures were prepared for polymerase chain ...

  9. Comment: Towards a Viable Local Government Structure in Nigeria ...

    African Journals Online (AJOL)

    Local governments are principally established for development at the grassroots and they must be structured in a manner that makes them viable and capable of achieving this purpose. The objective of this comment is to appraise the current local government structure under the Nigerian constitutional framework with a view ...

  10. Cultivation and multiplication of viable axenic Trypanosoma vivax in ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-09-01

    Sep 1, 2009 ... Cultivation and multiplication of viable axenic. Trypanosoma vivax in vitro and in vivo. O. A. Idowu, A. B. Idowu, C. F. Mafiana and S. O. Sam-Wobo*. Parasitology Laboratory, Department of Biological Sciences, University of Agriculture, Abeokuta, Nigeria. Accepted 13 April, 2006. Trypanosoma vivax was ...

  11. Detection of viable toxigenic Vibrio cholerae and virulent Shigella ...

    African Journals Online (AJOL)

    DRINIE

    2003-04-02

    Apr 2, 2003 ... A rapid and sensitive assay was developed for the detection of low numbers of viable Vibrio cholerae and Shigella spp. cells in environmental and drinking water samples. Water samples were filtered, and the filters were enriched in a non-selective medium. The enrichment cultures were prepared for ...

  12. High speed flow cytometric separation of viable cells

    Science.gov (United States)

    Sasaki, Dennis T.; Van den Engh, Gerrit J.; Buckie, Anne-Marie

    1995-01-01

    Hematopoietic cell populations are separated to provide cell sets and subsets as viable cells with high purity and high yields, based on the number of original cells present in the mixture. High-speed flow cytometry is employed using light characteristics of the cells to separate the cells, where high flow speeds are used to reduce the sorting time.

  13. 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

  14. The problem of psychopathology and phenomenology. What is viable and not viable in phenomenological psychiatry.

    Science.gov (United States)

    Ramos-Gorostiza, Pablo; Adán-Manes, Jaime

    2013-01-01

    The epistemological underpinnings of psychiatric theory and practice have always been unstable. This reflects the essential contradiction existing between the task (the description and individuation of speech and behavior as psychopathological symptoms) and tools (semiotics). As a result of this contradiction, the history of psychiatry is one of permanent crisis in which there are moments of temporary stability as approaches that aim at organizing this mismatch between tasks and tools gain prevalence. However, these approaches can only offer a false sense of unity, consistency and progress. In this sense, a narrow perspective on a particular period may lead us to believe that psychiatry is just another medical specialty with its own specific theoretical framework like others. However, any such perspective overlooks the coexistence of different schools, disagreements, contradictions, global alternatives, etc. For a certain period of time, phenomenology was assumed to be as the solution for psychiatry’s internal contradiction. As we see it, phenomenology was only partially understood. Despite the great influence it exerted upon psychiatry worldwide, it finally fell into disuse as a mere empiricism. Husserl’s phenomenology was more thoroughly understood and better assimilated by other psychiatrists, and its influence has persisted to the present day. If we view phenomenology in its proper (Husserlian) sense, it is possible to understand psychopathology as a means of creating intelligibility and clarifying the uniqueness of psychiatry. On the other hand, if phenomenology is understood as a representational theory, it will eventually lead to an unavoidable relapse into psychologism, which has been the main path of psychiatry until now.

  15. Therapeutic development in psoriasis.

    Science.gov (United States)

    Sobell, Jeffrey M; Leonardi, Craig L

    2014-06-01

    Advances in molecular biology have provided the basis for development of new therapeutic approaches to psoriasis. New, more effective therapies target specific molecules in the inflammatory cascade involved in the pathogenesis of psoriasis.The biologic era of psoriasis therapy began with inhibitors of T-cell activation, tumor necrosis factor-α, and interleukin (IL)-12/23. Continued investigation has led to therapies and therapeutic candidates that target IL-17, IL-23, phosphodiesterase-4, and isomers of Janus kinase. 2014 by Frontline Medical Communications Inc.

  16. A computational modelling approach combined with cellular electrophysiology data provides insights into the therapeutic benefit of targeting the late Na+ current

    Science.gov (United States)

    Yang, Pei-Chi; Song, Yejia; Giles, Wayne R; Horvath, Balazs; Chen-Izu, Ye; Belardinelli, Luiz; Rajamani, Sridharan; Clancy, Colleen E

    2015-01-01

    approach, our results suggest that INaL block is a potent therapeutic strategy. This is because reduction of INaL stabilizes the action potential waveform by reducing depolarizing current during the plateau phase of the action potential. This reduces the most vulnerable phase of the action potential with high membrane resistance. In summary, by reducing the sensitivity of the myocardial substrate to small electrical perturbations that promote arrhythmia triggers, agents such as GS-458967 may constitute an effective antiarrhythmic pharmacological strategy. Key points The ventricular action potential plateau is a phase of high resistance, which makes ventricular myocytes vulnerable to small electrical perturbations. We developed a computationally based model of GS-458967 interaction with the cardiac Na+ channel, informed by experimental data recorded from guinea pig isolated single ventricular myocytes. The model predicts that the therapeutic potential of GS-458967 derives largely from the designed property of significant potent selectivity for INaL. PMID:25545172

  17. PMA-PhyloChip DNA Microarray to Elucidate Viable Microbial Community Structure

    Science.gov (United States)

    Venkateswaran, Kasthuri J.; Stam, Christina N.; Andersen, Gary L.; DeSantis, Todd

    2011-01-01

    Since the Viking missions in the mid-1970s, traditional culture-based methods have been used for microbial enumeration by various NASA programs. Viable microbes are of particular concern for spacecraft cleanliness, for forward contamination of extraterrestrial bodies (proliferation of microbes), and for crew health/safety (viable pathogenic microbes). However, a "true" estimation of viable microbial population and differentiation from their dead cells using the most sensitive molecular methods is a challenge, because of the stability of DNA from dead cells. The goal of this research is to evaluate a rapid and sensitive microbial detection concept that will selectively estimate viable microbes. Nucleic acid amplification approaches such as the polymerase chain reaction (PCR) have shown promise for reducing time to detection for a wide range of applications. The proposed method is based on the use of a fluorescent DNA intercalating agent, propidium monoazide (PMA), which can only penetrate the membrane of dead cells. The PMA-quenched reaction mixtures can be screened, where only the DNA from live cells will be available for subsequent PCR reaction and microarray detection, and be identified as part of the viable microbial community. An additional advantage of the proposed rapid method is that it will detect viable microbes and differentiate from dead cells in only a few hours, as opposed to less comprehensive culture-based assays, which take days to complete. This novel combination approach is called the PMA-Microarray method. DNA intercalating agents such as PMA have previously been used to selectively distinguish between viable and dead bacterial cells. Once in the cell, the dye intercalates with the DNA and, upon photolysis under visible light, produces stable DNA adducts. DNA cross-linked in this way is unavailable for PCR. Environmental samples suspected of containing a mixture of live and dead microbial cells/spores will be treated with PMA, and then incubated

  18. READING PHILEMON AS THERAPEUTIC NARRATIVE

    African Journals Online (AJOL)

    2010-03-29

    Mar 29, 2010 ... Contrary to an initial impression, the narrative therapeutic approach does not emerge from a completely psychological ... Furthermore, a narrative therapeutic reading does not exist in a vacuum, therefore this investigation ..... converted to Christianity, Philemon supported other believers in various ways ...

  19. O atosibano como agente tocolítico: uma nova proposta de esquema terapêutico Atosiban as a tocolytic agent: a new proposal of a therapeutic approach

    Directory of Open Access Journals (Sweden)

    Fábio Roberto Cabar

    2008-02-01

    Full Text Available OBJETIVO: avaliar um novo esquema terapêutico de emprego do atosibano quanto ao efeito tocolítico, eficácia e efeitos colaterais maternos e fetais. MÉTODOS: Estudo prospectivo com 80 gestantes em trabalho de parto prematuro admitidas para tocólise. Critérios de inclusão: gestação única, presença de contrações uterinas regulares, dilatação cervical >1 cm e 50%, idade gestacional entre 23 e 33 semanas e seis dias, membranas ovulares íntegras, índice de líquido amniótico >5 e PURPOSE: to test a therapeutic approach using atosiban for tocolysis, evaluating its safety and maternal and fetal side effects. METHODS: prospective study with 80 pregnant women with preterm labor admitted for tocolysis. Inclusion criteria: singleton pregnancy, regular uterine activity, cervical dilatation between 1 to 3 cm, cervical enfacement greater than 50%, 23 to 33 weeks and six days of gestational age, intact membranes, amniotic fluid index between 5 and 25, no maternal, fetal or placental diseases, no fetal growth restriction, no cervical incompetence, no fever. Exclusion criteria: chorioamnionitis or fever during tocolysis. Atosiban group: women received 6.75 mg atosiban iv in bolus, 300 mcg/min for three hours, then 100 mcg/min for three hours and thirty minutes. If uterine activity persisted, it was maintained iv infusion of 100 mcg/min for 12.5 hand that so for as long as 45 hours. Control group: women received terbutaline (five ampoules, 500 mL crystalloid solution iv infusion, 20 mL/h. If uterine activity persisted, infusion velocity was raised (20 mL/h until uterine contractions were absent. The dose was maintained for 24 hours. RESULTS: gestational age at birth was 29 weeks and five days to 40 weeks and six days. In atosiban group, the proportion of women who had not delivered at 48 hours was 97.5%, mean interval between tocolysis and birth of 28.2 days. In control group, birth occurred before 48 hours in 22.5% of the cases; mean interval

  20. A technique for determining viable military logistics support alternatives

    Science.gov (United States)

    Hester, Jesse Stuart

    A look at today's US military will see them operating much beyond the scope of protecting and defending the United States. These operations now consist of, but are not limited to humanitarian aid, disaster relief, peace keeping, and conflict resolution. This broad spectrum of operational environments has necessitated a transformation of the individual military services to a hybrid force that is attempting to leverage the inherent and emerging capabilities and strengths of all those under the umbrella of the Department of Defense (DOD), this concept has been coined Joint Operations. Supporting Joint Operations requires a new approach to determining a viable military logistics support system. The logistics architecture for these operations has to accommodate scale, time, varied mission objectives, and imperfect information. Compounding the problem is the human in the loop (HITL) decision maker (DM) who is a necessary component for quickly assessing and planning logistics support activities. Past outcomes are not necessarily good indicators of future results, but they can provide a reasonable starting point for planning and prediction of specific needs for future requirements. Adequately forecasting the necessary logistical support structure and commodities needed for any resource intensive environment has progressed well beyond stable demand assumptions to one in which dynamic and nonlinear environments can be captured with some degree of fidelity and accuracy. While these advances are important, a holistic approach that allows exploration of the operational environment or design space does not exist to guide the military logistician in a methodical way to support military forecasting activities. To bridge this capability gap, a method called Adaptive Technique for Logistics Architecture Solutions (ATLAS) has been developed. This method provides a process that facilitates the use of techniques and tools that filter and provide relevant information to the DM. By doing

  1. Recovery of somatosensory and motor functions of the paretic upper limb in patients after stroke: Comparison of two therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Kateřina Macháčková

    2016-03-01

    Full Text Available Background: Frequent and extensive disturbances to the somatosensory and motor hand functions after stroke are common. This study explores a new therapeutic approach that may improve the effectiveness of rehabilitation for these upper limb impairments. Objective: To assess the effect of rehabilitation combining standard therapy and somatosensory stimulation on sensorimotor hand functions. To compare the effect of this method with the standard method of rehabilitation. Methods: Two groups of patients were used to compare the effect of standard therapy (group A, n = 15, age = 59.8 ± 9.4 years, and the effect of therapy with targeted somatosensory stimulation (group B, n = 15, age = 65.5 ± 8.2. The groups consisted of patients after an ischemic stroke in post-acute phase, with hemiparesis, aged from 45 to 75 years, both men and women. The methods used to assess patients comprised a neurological clinical examination, two batteries of tests of somatosensory function (Rivermead Assessment of Somatosensory Performance, Fabric Matching Test, two batteries of tests of motor function (Nine Hole Peg Test, Test of Manipulation Functions, and activities of daily living assessment. Results: The results show that before therapy a deficit of somatosensory function occurred on the paretic upper limb in more than 50% of patients in both groups. Motor functions were impaired more frequently than somatosensory functions. Somatosensory stimulation therapy had an enhanced improvement of somatosensory functions, especially tactile discrimination of the object surface. Conclusions: Major improvement, particularly of tactile discrimination sensation, occurred in group B, where therapy focused on somatosensory deficit was applied. We did not show that such considerable improvement in discrimination sensation in group B was associated with any change in motor function. Clinical improvement in the motor function of the paretic limb occurred in

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

    Science.gov (United States)

    Pétré, Benoit; Gagnayre, Remi; De Andrade, Vincent; Ziegler, Olivier; Guillaume, Michèle

    2017-01-01

    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 behavior. Best TPE practices should encourage personal work on this, opening professionals to the social, experiential and emotional aspects of managing chronic illness. PMID:28356722

  3. Viable group A streptococci in macrophages during acute soft tissue infection.

    Directory of Open Access Journals (Sweden)

    Pontus Thulin

    2006-03-01

    Full Text Available Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections

  4. Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis

  5. Removal of viable bacteria and endotoxins by Electro Deionization (EDI).

    Science.gov (United States)

    Harada, Norimitsu; Otomo, Teruo; Watabe, Tomoichi; Ase, Tomonobu; Takemura, Takuto; Sato, Toshio

    2011-09-01

    Viable bacteria and endotoxins in water sometimes cause problems for human health. Endotoxins are major components of the outer cell wall of gram-negative bacteria (lipopolysaccharides). In medical procedures, especially haemodialysis (HD) and related therapies (haemodiafiltration (HDF), haemofiltration (HF)), endotoxins in the water for haemodialysis can permeate through the haemodialysis membrane and cause microinflammation or various haemodialysis-related illnesses. To decrease such a biological risk, RO and UF membranes are generally used. Also, hot water disinfection or the chemical disinfection is regularly executed to kill bacteria which produce endotoxins. However, simple treatment methods and equipment may be able to decrease the biological risk more efficiently. In our experiments, we confirmed that viable bacteria and endotoxins were removed by Electro Deionization (EDI) technology and also clarified the desorption mechanisms.

  6. Acupuntura un tratamiento viable para las adicciones en Colombia

    Directory of Open Access Journals (Sweden)

    Hernán López Seuscún

    2013-07-01

    Los tratamientos con auriculoterapia, como el protocolo NADA (National Acupuncture Detoxification Association, son los métodos más usados para las adicciones en el mundo, y aunque no se ha logrado evidenciar su efectividad, por su costo, facilidad y el poco riesgo de efectos adversos se hace viable en un país con pocos recursos económicos como Colombia.

  7. Academic Pediatric Dentistry is a Rewarding, Financially Viable Career Path.

    Science.gov (United States)

    Townsend, Janice A; Chi, Donald L

    2017-09-15

    Newly graduated pediatric dentists have unprecedented levels of debt. High levels of student debt may be perceived as an obstacle to pursue an academic career. However, opportunities exist through faculty compensation models and loan repayment programs that make an academic career financially viable. The purpose of this paper is to outline the benefits of a career in academic dentistry and provide examples of young pediatric dentistry faculty members who have been able to manage student debt while pursuing meaningful and rewarding careers.

  8. How Can We Prevent Violence Becoming a Viable Political Strategy?

    OpenAIRE

    Patricia Justino

    2009-01-01

    A basic issue that conflict analysis investigates is how non-peaceful ways of living and governing become viable political strategies. Macro-level studies provide some important insights but micro-level analysis is vital to understand the mechanisms that make violence possible. This briefing outlines some preliminary findings in this respect from MICROCON, a major research programme analysing violent conflict at the micro level. It also discusses their implications for policies aimed at preve...

  9. A rapid biosensor for viable B. anthracis spores.

    Science.gov (United States)

    Baeumner, Antje J; Leonard, Barbara; McElwee, John; Montagna, Richard A

    2004-09-01

    A simple membrane-strip-based biosensor assay has been combined with a nucleic acid sequence-based amplification (NASBA) reaction for rapid (4 h) detection of a small number (ten) of viable B. anthracis spores. The biosensor is based on identification of a unique mRNA sequence from one of the anthrax toxin genes, the protective antigen ( pag), encoded on the toxin plasmid, pXO1, and thus provides high specificity toward B. anthracis. Previously, the anthrax toxins activator ( atxA) mRNA had been used in our laboratory for the development of a biosensor for the detection of a single B. anthracis spore within 12 h. Changing the target sequence to the pag mRNA provided the ability to shorten the overall assay time significantly. The vaccine strain of B. anthracis (Sterne strain) was used in all experiments. A 500-microL sample containing as few as ten spores was mixed with 500 microL growth medium and incubated for 30 min for spore germination and mRNA production. Thus, only spores that are viable were detected. Subsequently, RNA was extracted from lysed cells, selectively amplified using NASBA, and rapidly identified by the biosensor. While the biosensor assay requires only 15 min assay time, the overall process takes 4 h for detection of ten viable B. anthracis spores, and is shortened significantly if more spores are present. The biosensor is based on an oligonucleotide sandwich-hybridization assay format. It uses a membrane flow-through system with an immobilized DNA probe that hybridizes with the target sequence. Signal amplification is provided when the target sequence hybridizes to a second DNA probe that has been coupled to liposomes encapsulating the dye sulforhodamine B. The amount of liposomes captured in the detection zone can be read visually or quantified with a hand-held reflectometer. The biosensor can detect as little as 1 fmol target mRNA (1 nmol L(-1)). Specificity analysis revealed no cross-reactivity with 11 organisms tested, among them closely

  10. [Therapeutic management of neurodermatitis atopica].

    Science.gov (United States)

    Kägi, M K

    1998-08-01

    The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.

  11. Liquid biopsy in cancer patients: advances in capturing viable CTCs for functional studies using the EPISPOT assay.

    Science.gov (United States)

    Alix-Panabières, Catherine; Pantel, Klaus

    2015-01-01

    Circulating tumor cells (CTCs) in the blood of cancer patients have received increasing attention as new diagnostic tool enabling 'liquid biopsies'. In contrast to the wealth of descriptive studies demonstrating the clinical relevance of CTCs as biomarkers, the extremely low concentration of CTCs in the peripheral blood of most cancer patients challenges further functional studies. This article discusses the current possibilities to enrich and, in particular, detect viable CTCs with emphasis on the EPithelial ImmunoSPOT technology. This functional assay detects viable CTCs at the single-cell level and has been used on hundreds of patients with different tumor types including epithelial tumors (breast, prostate and colon cancer) and melanomas. Moreover, the article summarizes recent advances in the in vitro and in vivo expansion of CTCs from cancer patients. These functional analyses will contribute to identifying the biological properties of metastatic cells and reveal new therapeutic targets against disseminating cancer cells.

  12. 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

  13. Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones

    Directory of Open Access Journals (Sweden)

    Taylor Anthony H

    2011-11-01

    Full Text Available Abstract Background In early pregnancy, increased plasma levels of the endocannabinoid anandamide (AEA are associated with miscarriage through mechanisms that might affect the developing placenta or maternal decidua. Methods In this study, we compare AEA levels in failed and viable pregnancies with the levels of the trophoblastic hormones (beta-human chorionic gonadotrophin (beta-hCG, progesterone (P4 and (pregnancy-associated placental protein-A (PAPP-A essential for early pregnancy success and relate that to the expression of the cannabinoid receptors and enzymes that modulate AEA levels. Results The median plasma AEA level in non-viable pregnancies (1.48 nM; n = 20 was higher than in viable pregnancies (1.21 nM; n = 25; P = 0.013, as were progesterone and beta-hCG levels (41.0 vs 51.5 ng/mL; P = 0.052 for P4 and 28,650 vs 6,560