WorldWideScience

Sample records for thrombus therapeutic approach

  1. Angioplasty of symptomatic high-grade internal carotid artery stenosis with intraluminal thrombus: therapeutic approach

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, A.; Mayol, A. [Seccion de Neurorradiologia Intervencionista, Servicio de Radiologia, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain); Gil-Peralta, A.; Gonzalez-Marcos, J.R. [Servicio de Neurologia, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain); Boza, F. [Servicio de Neurofisiologia, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain); Ruano, J. [Unidad de Cuidados Intensivos, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013, Sevilla (Spain)

    2004-04-01

    Intraluminal thrombus in the internal carotid artery (ICA) is usually found in patients with severe atheromatous stenosis. Having reviewed 300 carotid angioplasties for symptomatic >70% ICA stenosis, we found three patients (1%) with intraluminal thrombus. Conservative treatment with anticoagulants and double antiplatelet coverage can result in lysis of the thrombus without severe risks. Percutaneous transluminal angioplasty and stenting, preferably with distal protection, can be an excellent alternative to carotid endarterectomy. (orig.)

  2. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

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

  3. 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.

  4. ‘Mother-in-child’ thrombectomy technique: a novel and effective approach to decrease intracoronary thrombus burden in acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Dauvergne, Christian; Araya, Mario [Department of Cardiology, Clinica Alemana, Santiago (Chile); Uriarte, Polentzi [Department of Cardiology, Instituto Nacional del Torax, Santiago (Chile); Novoa, Oscar; Novoa, Lilian [Department of Cardiology, Clinica Alemana, Santiago (Chile); Maluenda, Gabriel, E-mail: gabrielmaluenda@gmail.com [Department of Cardiology, Clinica Alemana, Santiago (Chile)

    2013-01-15

    Background: The presence of large thrombus burden in patients presenting with acute myocardial infarction (AMI) is common and associated with poor prognosis. This study aimed to describe the feasibility and safety of the novel ‘mother-in-child’ thrombectomy (MCT) technique in patients presenting with AMI and large thrombus burden undergoing percutaneous coronary intervention (PCI). Methods: We studied 13 patients presenting with AMI who underwent PCI with persistent large intracoronary thrombus after standard thrombectomy. The procedure was performed using a 5 F ‘Heartrail II-ST01’ catheter (Terumo Medical) into a 6 F guiding system. Angiographic assessment of thrombus burden and coronary flow was obtained at baseline, immediately after thrombectomy and at the end of the procedure. Results: The mean age was 55.9 ± 13.0 years and involved mostly males (76.9%). All patients underwent PCI via radial approach. Following MCT Thrombolysis In Myocardial Infarction (TIMI) flow improved by 2 or more degrees in 11 patients (84.5%), while visible angiographic thrombus was reduced in 11 patients (84.5%). In the final angiogram, normal TIMI flow was restored in 11 patients (84.5%), with normal myocardial ‘blush’ in 7 patients (53.8%) and total clearance of a visible thrombus in 7 patients (53.8%). Overall, 6 patients received thrombectomy as ‘stand-alone’ procedure. All patients were discharged alive after a mean of 5.6 ± 2 days. Conclusion: This initial report suggests that significant reduction in thrombus burden and improvement of the coronary flow can be safely achieved in patients presenting with AMI and large thrombus burden by using the novel MCT technique.

  5. Syncope: therapeutic approaches.

    Science.gov (United States)

    Benditt, David G; Nguyen, John T

    2009-05-12

    Syncope is a common clinical problem characterized by transient, spontaneously self-terminating loss of consciousness with complete and prompt recovery; the cause is insufficiency of cerebral oxygen/nutrient supply most often due to a transient fall of systemic arterial pressure to levels below those tolerated by cerebrovascular autoregulation. Careful and thorough evaluation of the cause of syncope is warranted in all patients. Determining that certain individuals are at "low mortality risk" is inadequate; syncope, although often benign from a mortality perspective, tends to recur, is associated with risk of physical injury, diminishes quality-of-life, and might lead to restriction from employment or avocation. However, the diagnostic evaluation and treatment of syncope is challenging for many reasons. First, syncope is only 1 of many causes of transient loss of consciousness. Second, the patient's symptoms are fleeting, and the patient is generally fully recovered when seen in the clinic; only infrequently are there helpful physical findings. Third, spontaneous events are often unwitnessed by medical professionals; consequently, the medical history of symptom events is usually a "second-hand" or "third-hand" story. Finally, there is often an excessive sense of diagnostic "urgency" that tends to result in a rush to undertake multiple poorly considered "diagnostic" testing procedures; a deliberate approach based on initial risk stratification is more likely to reap the dual rewards of a correct diagnosis and initiation of effective treatment in a cost-effective manner.

  6. Thrombus-aspiration through 5 Fr guiding catheter with transradial approach in acute coronary syndromes: feasibility of a mini-invasive strategy.

    Science.gov (United States)

    Roule, Vincent; Dahdouh, Ziad; Wain-Hobson, Julien; Bignon, Mathieu; Malcor, Guillaume; Lognoné, Thérèse; Milliez, Paul; Grollier, Gilles; Sabatier, Rémi

    2012-08-01

    The purpose of this study was to assess the feasibility and safety of thrombus-aspiration through a 5 Fr guiding catheter with transradial approach in acute coronary syndromes. The use of thrombus-aspirating devices improves myocardial reperfusion but requires at least a 6 Fr guiding catheter. Transradial coronary interventions using a 5 Fr guiding catheter are attractive to reduce bleeding complications. We retrospectively selected patients presenting acute coronary syndromes with angiographically visible thrombus who underwent thrombus-aspiration through radial access using a 4 Fr multipurpose catheter in a 5 Fr guiding catheter. We described clinical and angiographic characteristics of the cohort, and the procedure's technique, success and complications. Among the 34 included patients, 29 presented ST-segment elevation myocardial infarction. Complete resolution of the ST-segment elevation was effective in 93% of these patients. TIMI flow grade after thrombus-aspiration was significantly improved compared to baseline TIMI flow grade or after passage of the guidewire (P guiding catheter with transradial approach seems to be safe and effective in selected patients with acute coronary syndrome. This mini-invasive approach brought the advantages of the transradial access in 5 Fr but also its limitations. ©2012, Wiley Periodicals, Inc.

  7. 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

  8. Therapeutic approach to epileptic encephalopathies.

    Science.gov (United States)

    Vigevano, Federico; Arzimanoglou, Alexis; Plouin, Perrine; Specchio, Nicola

    2013-11-01

    Epileptic encephalopathies (EEs) are electroclinical entities with a peculiar course of disease; seizures and electroencephalographic (EEG) epileptiform abnormalities, ictal and interictal, contribute to progressive disturbance of cerebral functions. Frequently EEs are drug resistant, and consequences may be catastrophic. The main goal of treatment is to stop the peculiar course of epilepsy, operating on three parameters: seizure control, reduction of EEG abnormalities, and developmental outcome. For a correct therapeutic approach it is mandatory to have an as accurate as possible syndromic and etiologic diagnosis. Given the poor efficacy of conventional antiepileptic drugs (AEDs), the use of specific drugs for EEs, such as adrenocorticotropic hormone (ACTH) and corticosteroids or stiripentol is suggested. In some cases the choice of treatment is strictly related to the etiology: vigabatrin in tuberous sclerosis, ketogenic diet in glucose transporter type 1 (GLUT-1) deficiency, and pyridoxine in pyridoxine deficiency. Some AEDs combinations, such as sodium valproate with lamotrigine, have also provided interesting results, for example, in Lennox-Gastaut syndrome, although controlled studies are lacking. Finally, early surgery can be an option in children with focal structural abnormalities responsible for EEs preferably before irreversible damage on developmental outcome. Multispecialist support is recommended in EE. Management should be global from the onset, integrating not only seizure control but also all issues related to comorbidities, particularly neuropsychological and psychiatric. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  9. Identification and Management of Pump Thrombus in the HeartWare Left Ventricular Assist Device System: A Novel Approach Using Log File Analysis.

    Science.gov (United States)

    Jorde, Ulrich P; Aaronson, Keith D; Najjar, Samer S; Pagani, Francis D; Hayward, Christopher; Zimpfer, Daniel; Schlöglhofer, Thomas; Pham, Duc T; Goldstein, Daniel J; Leadley, Katrin; Chow, Ming-Jay; Brown, Michael C; Uriel, Nir

    2015-11-01

    The study sought to characterize patterns in the HeartWare (HeartWare Inc., Framingham, Massachusetts) ventricular assist device (HVAD) log files associated with successful medical treatment of device thrombosis. Device thrombosis is a serious adverse event for mechanical circulatory support devices and is often preceded by increased power consumption. Log files of the pump power are easily accessible on the bedside monitor of HVAD patients and may allow early diagnosis of device thrombosis. Furthermore, analysis of the log files may be able to predict the success rate of thrombolysis or the need for pump exchange. The log files of 15 ADVANCE trial patients (algorithm derivation cohort) with 16 pump thrombus events treated with tissue plasminogen activator (tPA) were assessed for changes in the absolute and rate of increase in power consumption. Successful thrombolysis was defined as a clinical resolution of pump thrombus including normalization of power consumption and improvement in biochemical markers of hemolysis. Significant differences in log file patterns between successful and unsuccessful thrombolysis treatments were verified in 43 patients with 53 pump thrombus events implanted outside of clinical trials (validation cohort). The overall success rate of tPA therapy was 57%. Successful treatments had significantly lower measures of percent of expected power (130.9% vs. 196.1%, p = 0.016) and rate of increase in power (0.61 vs. 2.87, p Log file parameters can potentially predict the likelihood of successful tPA treatments and if validated prospectively, could substantially alter the approach to thrombus management. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Malignant mesothelioma: biology, diagnosis and therapeutic approaches

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

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

  11. Interpreting quantum theory a therapeutic approach

    CERN Document Server

    Friederich, S

    2014-01-01

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

  12. Dissolution of pre-existing platelet thrombus by synergistic administration of low concentrations of bifunctional antibodies against β3 integrin.

    Directory of Open Access Journals (Sweden)

    Suying Dang

    Full Text Available Most antithrombotic approaches target prevention rather than the more clinically relevant issue of resolution of an existing thrombus. In this study, we describe a novel and effective therapeutic strategy for ex vivo clearance of pre-existing platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66 ligands that target different parts of the arterial thrombus. We produced an additional GPIIIa49-66 agent (named APAC, which homes to activated platelets. Like our previously described SLK (which targets newly deposited fibrin strands surrounding the platelet thrombus, APAC destroys platelet aggregates ex vivo in an identical fashion with 85% destruction of platelet aggregates at 2 hours. The combined application of APAC and SLK demonstrated a ~2 fold greater platelet thrombus dissolution than either agent alone at a low concentration (0.025 µM. Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T(50% by APAC (95 ± 6.1 min or SLK (145 ± 7.1 min was much longer than that by combined APAC + SLK (65 ± 7.6 min at the final concentration of 0.025 µM (APAC + SLK vs APAC, p<0.05; APAC + SLK vs SLK, p<0.01. Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo.

  13. Dissolution of pre-existing platelet thrombus by synergistic administration of low concentrations of bifunctional antibodies against β3 integrin.

    Science.gov (United States)

    Dang, Suying; Hong, Tao; Wisniewski, Thomas; Zhang, Wei

    2011-01-01

    Most antithrombotic approaches target prevention rather than the more clinically relevant issue of resolution of an existing thrombus. In this study, we describe a novel and effective therapeutic strategy for ex vivo clearance of pre-existing platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66 ligands that target different parts of the arterial thrombus. We produced an additional GPIIIa49-66 agent (named APAC), which homes to activated platelets. Like our previously described SLK (which targets newly deposited fibrin strands surrounding the platelet thrombus), APAC destroys platelet aggregates ex vivo in an identical fashion with 85% destruction of platelet aggregates at 2 hours. The combined application of APAC and SLK demonstrated a ~2 fold greater platelet thrombus dissolution than either agent alone at a low concentration (0.025 µM). Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T(50%)) by APAC (95 ± 6.1 min) or SLK (145 ± 7.1 min) was much longer than that by combined APAC + SLK (65 ± 7.6 min) at the final concentration of 0.025 µM (APAC + SLK vs APAC, pAPAC + SLK vs SLK, p<0.01). Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo.

  14. Right heart thrombus in transit: a series of two cases.

    Science.gov (United States)

    Otoupalova, Eva; Dalal, Bhavinkumar; Renard, Brian

    2017-12-01

    Right heart thrombus in transit is an increasingly recognized medical emergency with very high mortality rate. Echocardiography helps to establish the diagnosis and can differentiate between right heart thrombi that result from atrial fibrillation and those originating from deep venous thrombosis. We present two cases of right heart thrombus in transit diagnosed with echocardiography that were managed with different approaches.

  15. [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.

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

    Science.gov (United States)

    Alsharif, Naser Z.; And Others

    1997-01-01

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

  17. 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.

  18. 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.

  19. New approaches to molecular cancer therapeutics.

    Science.gov (United States)

    Collins, Ian; Workman, Paul

    2006-12-01

    Cancer drug development is leading the way in exploiting molecular biological and genetic information to develop "personalized" medicine. The new paradigm is to develop agents that target the precise molecular pathology driving the progression of individual cancers. Drug developers have benefited from decades of academic cancer research and from investment in genomics, genetics and automation; their success is exemplified by high-profile drugs such as Herceptin (trastuzumab), Gleevec (imatinib), Tarceva (erlotinib) and Avastin (bevacizumab). However, only 5% of cancer drugs entering clinical trials reach marketing approval. Cancer remains a high unmet medical need, and many potential cancer targets remain undrugged. In this review we assess the status of the discovery and development of small-molecule cancer therapeutics. We show how chemical biology approaches offer techniques for interconnecting elements of the traditional linear progression from gene to drug, thereby providing a basis for increasing speed and success in cancer drug discovery.

  20. GIANT PROSTHETIC VALVE THROMBUS

    Directory of Open Access Journals (Sweden)

    Prashanth Kumar

    2015-04-01

    Full Text Available Mechanical prosthetic valves are predisposed to bleeding, thrombosis & thromboembolic complications. Overall incidence of thromboembolic complications is 1% per year who are on oral anticoagulants, whereas bleeding complications incidence is 0.5% to 6.6% per year. 1, 2 Minimization of Scylla of thromboembolic & Charybdis of bleeding complication needs a balancing act of optimal antithrombotic therapy. We are reporting a case of middle aged male patient with prosthetic mitral valve presenting in heart failure. Patient had discontinued anticoagulants, as he had subdural hematoma in the past. He presented to our institute with a giant prosthetic valve thrombus.

  1. 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

  2. Dabigatran for left ventricular thrombus

    Directory of Open Access Journals (Sweden)

    Satishkumar Kolekar

    2015-09-01

    Dabigatran is a reversible direct thrombin inhibitor and currently approved for the prevention of thromboembolic episodes in non-valvar atrial fibrillation. This case demonstrates possible thrombolytic properties of dabigatran in resolution of left ventricular thrombus.

  3. 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.

  4. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

    Directory of Open Access Journals (Sweden)

    Chase W Kessinger

    Full Text Available Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT will develop the post-thrombotic syndrome (PTS. Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice. Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1, tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs, and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

  5. Tractatus; The beginning of Wittgenstein's therapeutic approach to philosophy

    Directory of Open Access Journals (Sweden)

    Sahar

    2015-10-01

    Full Text Available On the one hand, Wittgenstein considers philosophy as a generator of mental confusion, but on the other hand, he desires philosopher as a therapist. This two-sided attitude to philosophy begins with Tractatus and then admitting the various therapeutic methods, reaches to the second period of his life. Recently, the origins of Wittgenstein's therapeutic approach in Tractatus are neglected by most of his positivist commentators, instead, this approach have been followed in the second period of his thought, especially in Philosophical Investigations. In this essay, we have tried to clarify this obscurity and to indicate the roots of Wittgenstein's therapeutic approach in Tractatus. Since mentioning the "symptom" or symptoms of mental confusion resulting from philosophical thinking and stage of its "diagnosis" is considered as preparations of therapy, we, by emphasizing on the therapeutic value of clarity, will survey "symptom", "diagnosis" and finally Wittgenstein's therapeutic approach toward philosophy in Tractatus, and then we will point out some reasons causing negligence to Tractatus therapeutic approach. In this way, we will show that Wittgenstein, from the beginning of his philosophical thinking, has believed in this approach and in Philosophical Investigations he has just declared it in the everyday language. Here, we will also unveil restriction of Wittgenstein's therapeutic approach to philosophy.

  6. 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.

  7. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    Pacheco, Ivan; Buzea, Cristina; Tron, Victor

    2011-11-01

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

  8. Recent novel tumor gatekeepers and potential therapeutic approaches

    African Journals Online (AJOL)

    In this review, efforts 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, ...

  9. 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.

  10. Nanotechnology based approaches in cancer therapeutics

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  11. [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.

  12. 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.

  13. 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.

  14. Therapeutic Approaches to Target Cancer Stem Cells

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

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

  15. Generic thrombus segmentation from pre- and post-operative CTA.

    Science.gov (United States)

    Lalys, Florent; Yan, Vincent; Kaladji, Adrien; Lucas, Antoine; Esneault, Simon

    2017-09-01

    Abdominal aortic aneurysm (AAA) is a localized, permanent and irreversible enlargement of the artery, with the formation of thrombus into the inner wall of the aneurysm. A precise patient-specific segmentation of the thrombus is useful for both the pre-operative planning to estimate the rupture risk, and for post-operative assessment to monitor the disease evolution. This paper presents a generic approach for 3D segmentation of thrombus from patients suffering from AAA using computed tomography angiography (CTA) scans. A fast and versatile thrombus segmentation approach has been developed. It is composed of initial centerline detection and aorta lumen segmentation, an optimized pre-processing stage and the use of a 3D deformable model. The approach has been designed to be very generic and requires minimal user interaction. The proposed method was tested on different datasets with 145 patients overall, including pre- and post-operative CTAs, abdominal aorta and iliac artery sections, different calcification degrees, aneurysm sizes and contrast enhancement qualities. The thrombus segmentation approach showed very accurate results with respect to manual delineations for all datasets ([Formula: see text] and [Formula: see text] for abdominal aorta sections on pre-operative CTA, iliac artery sections on pre-operative CTAs and aorta sections on post-operative CTA, respectively). Experiments on the different patient and image conditions showed that the method was highly versatile, with no significant differences in term of precision. Comparison with the level-set algorithm also demonstrated the superiority of the 3D deformable model. Average processing time was [Formula: see text]. We presented a near-automatic and generic thrombus segmentation algorithm applicable to a large variability of patient and imaging conditions. When integrated in an endovascular planning system, our segmentation algorithm shows its compatibility with clinical routine and could be used for pre

  16. [The therapeutic approach to drug addicts].

    Science.gov (United States)

    Bucher, R E; Costa, P F

    1985-06-01

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

  17. Tumor thrombus of inferior vena cava in patients with renal cell carcinoma – clinical and oncological outcome of 50 patients after surgery

    Directory of Open Access Journals (Sweden)

    Kocot Arkadius

    2012-06-01

    Full Text Available Abstract Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC and tumor thrombus involving inferior vena cava (IVC treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42% distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%, thoracoabdominal (14 patients/28% or midline abdominal approach (21 patients/42%, depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB was performed in 10 patients (20% with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10 even had a better outcome (overall survival at 5 years of 58.33% than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal

  18. Multiple, sclerosis: clinical feature, pathogenesis and current therapeutical approaches

    International Nuclear Information System (INIS)

    Merkelbach, S.; Koelmel, C.; Schimrigk, K.

    2000-01-01

    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.) [de

  19. Patient in chronic hemodialysis with right atrial mass: thrombus, fungal endocarditis or atrial myxoma?

    Science.gov (United States)

    Salani, Talita G; Borges, Cynthia de Moura; Urbini, Carolina S; Schincariol, Patrícia; Quadros, Kélcia Rosana da Silva; Ribeiro-Alves, Maria Almerinda; Oliveira, Rodrigo Bueno de

    2016-12-01

    We present the case report of a 19-year-old patient with chronic kidney disease due to chronic glomerulonephritis, in hemodialysis (HD) by central catheter, with the incidental finding of a mass of 28x16 mm in right atrium (RA). The diagnosis of thrombus, infective endocarditis or myxoma were considered. Given the context of immunosuppression and difficult access vascular therapeutic practice has proved complex. Although Doppler echocardiography suggested thrombus in RA, nuclear magnetic resonance imaging (MRI) indicated for the diagnosis of myxoma in RA. In both conditions, the proposed surgical approach was limited by intense immunosuppression history and the risk of infectious complications. Throughout the treatment, the general state of K.M.F. remained satisfactory and revealed no signs or symptoms related to atrial dysfunction. The absence of fever and negative blood cultures excluded infective endocarditis. Prior echocardiogram report without masses in the RA decreased the chance of cardiac myxoma. The therapeutic response to anticoagulation confirmed the diagnosis of thrombosis. After 180 days of anticoagulation, there was significant reduction in mass. The patient developed asymptomatic. The diagnosis of mass in RA can be a challenge and only the evolution of the case was able to guide the appropriate conduit. While MRI has high sensitivity and specificity for the diagnosis of cardiac myxoma, the interpretation of images can be subjective. Controversial point is the removal of the catheter in such cases, which is subject discussed throughout the report.

  20. Thrombus segmentation by texture dynamics from microscopic image sequences

    Science.gov (United States)

    Brieu, Nicolas; Serbanovic-Canic, Jovana; Cvejic, Ana; Stemple, Derek; Ouwehand, Willem; Navab, Nassir; Groher, Martin

    2010-03-01

    The genetic factors of thrombosis are commonly explored by microscopically imaging the coagulation of blood cells induced by injuring a vessel of mice or of zebrafish mutants. The latter species is particularly interesting since skin transparency permits to non-invasively acquire microscopic images of the scene with a CCD camera and to estimate the parameters characterizing the thrombus development. These parameters are currently determined by manual outlining, which is both error prone and extremely time consuming. Even though a technique for automatic thrombus extraction would be highly valuable for gene analysts, little work can be found, which is mainly due to very low image contrast and spurious structures. In this work, we propose to semi-automatically segment the thrombus over time from microscopic image sequences of wild-type zebrafish larvae. To compensate the lack of valuable spatial information, our main idea consists of exploiting the temporal information by modeling the variations of the pixel intensities over successive temporal windows with a linear Markov-based dynamic texture formalization. We then derive an image from the estimated model parameters, which represents the probability of a pixel to belong to the thrombus. We employ this probability image to accurately estimate the thrombus position via an active contour segmentation incorporating also prior and spatial information of the underlying intensity images. The performance of our approach is tested on three microscopic image sequences. We show that the thrombus is accurately tracked over time in each sequence if the respective parameters controlling prior influence and contour stiffness are correctly chosen.

  1. The Use of a Therapeutic Jurisprudence Approach to the Teaching ...

    African Journals Online (AJOL)

    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 ...

  2. Novel therapeutic approaches for hepatocellulcar carcinoma: fact and fiction.

    Science.gov (United States)

    Zhang, Yuan-Yuan; Xia, Harry-Hua-Xiang

    2008-03-21

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and accounts for 80%-90% of this class of malignancy. So far, understanding of its pathogenesis and effective therapeutic methods are rather limited. In this issue, 11 invited review articles are published to address current advance of underlying molecular mechanisms for the development of HCC, and novel therapeutic approaches for HCC. This series of review articles provide an in-depth unders-tanding of HCC that has led to or may lead to the development of novel therapies for HCC.

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

    Directory of Open Access Journals (Sweden)

    Viktoriia A. Lykova

    2010-08-01

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

  4. Surgical Treatment of Renal Cell Carcinoma with Inferior Vena Cava Thrombus: Using Liver Mobilization Technique to Avoid Cardiopulmonary Bypass

    Directory of Open Access Journals (Sweden)

    Tawatchai Taweemonkongsap

    2008-04-01

    CONCLUSION: These results support the aggressive surgical removal of RCC with IVC thrombus as the initial treatment. Most of the thrombi can be approached and safely controlled by a transabdominal approach without any form of bypass. Tumour thrombus removal provides a high survival chance and offers improvement in quality of life.

  5. Development of a flow-through system to create occluding thrombus.

    Science.gov (United States)

    Ku, David N; Flannery, Conor J

    2007-01-01

    Occlusive thrombosis accounts for many heart attacks and strokes. These acute events are difficult to catch in patients and animal test methods may be misleading because anti-thrombotic therapeutics often do not cross-react with different species. This paper presents a new flow-through system that leads to rapid occlusive thrombosis in arterial flow conditions. Whole porcine blood is perfused through a tubular test section. The growing thrombus is visualized in real time from early platelet attachment, through accumulation, to occlusion. The progression of flow rate reduction provides a clear distinguishing parameter between thrombus formation and embolization. Thrombus growth rate is a linear function of very high shear rate beyond 40,000 s(-1). The histology of the thrombus reveals predominantly platelet accumulation and growth as a rough surface with tendrils. This flow-through system may be useful for the economic testing of new anti-thrombosis therapies.

  6. NANO TECHNOLOGY: A NEW THERAPEUTIC APPROACH FOR DIABETES

    OpenAIRE

    K. Sai Sasank *1 , Dr. Greeshma Musunuru2 , Nalluri Kranthi Koushik 1 , Dr. R. Venkateswara Rao2 , Dr. Ramarao Nadendla3

    2017-01-01

    Nano technology an exciting area of scientific development offers ways to create smaller, cheaper, lighter devices that can help to do better. The current literature has recognized and reported many possibility and applications of nano technology. The medical applications of nano technology are tremendous and could give medicine including the treatment of diabetes a new therapeutic approach. The frequency of diabetes is growing rapidly all over the globe at an alarming rate. Hence, the applic...

  7. NANO TECHNOLOGY: A NEW THERAPEUTIC APPROACH FOR DIABETES

    OpenAIRE

    K. Sai Sasank * , Dr. Greeshma Musunuru , Nalluri Kranthi Koushik , Dr. R. Venkateswara Rao , Dr. Ramarao Nadendla

    2016-01-01

    Nano technology an exciting area of scientific development offers ways to create smaller, cheaper, lighter devices that can help to do better. The current literature has recognized and reported many possibility and applications of nano technology. The medical applications of nano technology are tremendous and could give medicine including the treatment of diabetes a new therapeutic approach. The frequency of diabetes is growing rapidly all over the globe at an alarming rate. Hence, the applic...

  8. Dynamics of blood flow and thrombus formation in a multi-bypass microfluidic ladder network.

    Science.gov (United States)

    Zilberman-Rudenko, Jevgenia; Sylman, Joanna L; Lakshmanan, Hari H S; McCarty, Owen J T; Maddala, Jeevan

    2017-02-01

    The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL. Red blood cells and platelets were assumed to be non-interacting spherical particles transported by the bulk fluid flow, and convection of the activated coagulation factor II, thrombin, was assumed to be governed by mass transfer. This model served as the basis for predicting formation of local shear rate gradients, stagnation points and recirculation zones as dictated by the bypass geometry. Based on the insights from these models, we were able to predict the patterns of blood clot formation at specific locations in the device. Our experimental data was then used to adjust the model to account for the dynamical presence of thrombus formation in the biorheology of blood flow. The model predictions were then compared to results from experiments using recalcified whole human blood. Microfluidic devices were coated with the extracellular matrix protein, fibrillar collagen, and the initiator of the extrinsic pathway of coagulation, tissue factor. Blood was perfused through the devices at a flow rate of 2 µL/min, translating to physiologically relevant initial shear rates of 300 and 700 s -1 for main channels and bypasses, respectively. Using fluorescent and light microscopy, we observed distinct flow and thrombus formation patterns near channel intersections at bypass points, within recirculation zones and at stagnation points. Findings from this proof-of-principle ladder network model suggest a specific correlation between

  9. siRNA Genome Screening Approaches to Therapeutic Drug Repositioning

    Directory of Open Access Journals (Sweden)

    Ralph A. Tripp

    2013-01-01

    Full Text Available Bridging high-throughput screening (HTS with RNA interference (RNAi has allowed for rapid discovery of the molecular basis of many diseases, and identification of potential pathways for developing safe and effective treatments. These features have identified new host gene targets for existing drugs paving the pathway for therapeutic drug repositioning. Using RNAi to discover and help validate new drug targets has also provided a means to filter and prioritize promising therapeutics. This review summarizes these approaches across a spectrum of methods and targets in the host response to pathogens. Particular attention is given to the utility of drug repurposing utilizing the promiscuous nature of some drugs that affect multiple molecules or pathways, and how these biological pathways can be targeted to regulate disease outcome.

  10. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

  12. [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.

  13. Microbubble mediated thrombus dissolution with diagnostic ultrasound for the treatment of chronic venous thrombi.

    Directory of Open Access Journals (Sweden)

    Shelby Kutty

    Full Text Available Central venous catheter (CVC thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB enhanced sonothrombolysis for aged CVC associated thrombi in vivo.A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments. Baseline intracardiac echocardiography (ICE, 10.5F, Siemens, fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI two-dimensional US treatments (1.1-1.7 MI; iE33, Philips applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox were visualized near the thrombus (n = 10; Group A. Control pigs (n = 10; Group B received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm(2 respectively in Group A; compared to 0.24 and 0.21 cm(2 in Group B (p  = 0.0003. Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4, which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment.Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

  14. RECURRENT ORAL CANCER: CURRENT AND EMERGING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Sabrina Daniela Silva

    2012-07-01

    Full Text Available Oral cancer cavity (OCC is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.

  15. Superior Venacava Thrombus-A Case Report

    Directory of Open Access Journals (Sweden)

    Bijay Sah

    2016-03-01

    Full Text Available Superior venacava (SVC thrombus is a condition requiring immediate diagnosis and treatment. SVC thrombus causes obstruction of blood flow through the SVC resulting in severe decrease in venous return from the head, neck and upper extremity to the heart. The presenting symptoms of SVC obstruction include headache, hoarseness of voice, dyspnea, and laryngeal edema, dizziness, swelling of face, neck, and upper extremity. We hereby present a case of SVC thrombus who presented to the casualty department of COMS-TH with features of SVC syndrome which was diagnosed and managed promptly.JCMS Nepal. 2016;12(1:33-5.

  16. Acute Abdominal Mobile Aortic Thrombus Post Chemotherapy: Two Cases Reports

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Chul; Kim, Jun Ho; Lee, Kyung Hee; Cho, Soon Gu; Jeon, Yong Sun [Dept. of Radiology, Inha University School of Medicine, Incheon (Korea, Republic of)

    2011-08-15

    An acute abdominal mobile aortic thrombus is a very unusual finding, and this is a potential source of arterial embolism. Mobile aortic thrombus mostly occurs in a diffuse atherosclerotic and aneurysmal aorta. Chemotherapy agents have been documented as a possible rare cause of acute arterial thrombus. We report acute abdominal mobile aortic thrombus post-chemotherapy for pancreatic and stomach cancer.

  17. 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...

  18. 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.

  19. Antibody-targeted thrombus imaging and thrombolysis

    International Nuclear Information System (INIS)

    Wu Guoxin; Ruan Changgeng

    1993-05-01

    In respect of thrombus imaging, the femoral arterial or venous thrombus model was prepared in dogs and imaged with single photon emission computerized tomography (SPECT). After 4 hours of injection of 131 I-SZ-51 the radioactivity ratio between thrombus and blood (T/B) was 18 : 1 and 8 : 1 for arterial and venous thrombus respectively. The result conformed with the T/B ratio of the removed thrombus and blood after 24 hours of injection of radiotracer. It indicates that the McAb SZ-51 has a great potential to bind with thrombus. In respect of thrombolysis, the Fab(fragment, antigen-binding) fragment of McAb SZ-51 was chemically conjugated of urokinase (UK) by the disulfide-linking reagent SPDP and 2-iminothiolane. The resulting conjugate was 3 to 5 times as potent as UK in vitro in human platelet-rich plasma assay. The increase of fibrinolytic potency was accompanied by a decrease of consumption of plasminogen and fibrinogen. It shows that the increase of potency is the result of selectivity increase

  20. Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy

    Science.gov (United States)

    Tisdale, Sarah

    2015-01-01

    Motor neuron diseases are neurological disorders characterized primarily by the degeneration of spinal motor neurons, skeletal muscle atrophy, and debilitating and often fatal motor dysfunction. Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease of high incidence and severity and the most common genetic cause of infant mortality. SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene and retention of at least one copy of the hypomorphic gene paralog SMN2. Early studies established a loss-of-function disease mechanism involving ubiquitous SMN deficiency and suggested SMN upregulation as a possible therapeutic approach. In recent years, greater knowledge of the central role of SMN in RNA processing combined with deep characterization of animal models of SMA has significantly advanced our understanding of the cellular and molecular basis of the disease. SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types. Advances in SMA research have also led to the development of several potential therapeutics shown to be effective in animal models of SMA that are now in clinical trials. These agents offer unprecedented promise for the treatment of this still incurable neurodegenerative disease. PMID:26063904

  1. Gummy smile: clinical parameters useful for diagnosis and therapeutical approach.

    Science.gov (United States)

    Monaco, Annalisa; Streni, Oriana; Marci, Maria Chiara; Marzo, Giuseppe; Gatto, Roberto; Giannoni, Mario

    2004-01-01

    In the analysis of the characteristics of a pleasant smile, a gummy smile has negative components, which most affect the esthetics of non-verbal communication. For this purpose a proposed classification based upon etiopathogenetic criteria as useful indications for a therapeutical approach is given. The nature of a high smile line can be: dento-gingival, connected to an abnormal dental eruption, which is revealed by a short clinic crown; muscular, caused by an hyperactivity of the elevator muscle of the upper lip; dento-alveolar (skeletal), due to an excessive protuberance or vertical growth of the jawbone (maxillary); lastly, a mixed nature, in the presence of more than one of the above described factors The diagnosis of gummy smile must be precocious and based, with reference to specific parameters, upon a careful analysis of the etiopathogenetic factors and the degree of seriousness of the alteration. A correct treatment plan must contemplate the possibility of an orthognatodontic, orthopedic and/or surgical therapeutic resolution considering the seriousness and complexity of the gums exposures (high smile line) in connection with the age of the subject.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    Maria A. Sortino

    2017-06-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2018-01-01

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

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

    Science.gov (United States)

    Gomes, Fernanda; Henriques, Mariana

    2016-04-01

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

  6. [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.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Raj Kumar

    2011-01-01

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

  10. [Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

    Science.gov (United States)

    Tsuji, Daisuke

    2013-01-01

    Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice.

  11. 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

  12. Novel approach to cancer therapeutics using comparative cancer biology

    OpenAIRE

    Revi, Bhindu

    2018-01-01

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

  13. 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.

  14. 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.

  15. 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

  16. Emerging therapeutics for advanced thyroid malignancies: rationale and targeted approaches.

    Science.gov (United States)

    Harris, Pamela Jo; Bible, Keith C

    2011-10-01

    Thyroid cancer is an emerging public health concern. In the USA, its incidence has doubled in the past decade, making it the eighth most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity-modulated radiation therapy appears to extend survival for patients with locoregionally confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes.

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

    Directory of Open Access Journals (Sweden)

    Mario Stampanoni Bassi

    2017-12-01

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

  18. Detection of extracellular genomic DNA scaffold in human thrombus

    DEFF Research Database (Denmark)

    Oklu, Rahmi; Albadawi, Hassan; Watkins, Michael T

    2012-01-01

    PURPOSE: Mechanisms underlying transition of a thrombus susceptible to tissue plasminogen activator (TPA) fibrinolysis to one that is resistant is unclear. Demonstration of a new possible thrombus scaffold may open new avenues of research in thrombolysis and may provide mechanistic insight...... into thrombus remodeling. MATERIALS AND METHODS: Ten human thrombus samples were collected during cases of thrombectomy and open surgical repair of abdominal aortic aneurysms (five samples 1 y old). Additionally, an acute murine hindlimb ischemia model was created to evaluate...

  19. Licochalcone A Prevents Platelet Activation and Thrombus Formation through the Inhibition of PLCγ2-PKC, Akt, and MAPK Pathways.

    Science.gov (United States)

    Lien, Li-Ming; Lin, Kuan-Hung; Huang, Li-Ting; Tseng, Mei-Fang; Chiu, Hou-Chang; Chen, Ray-Jade; Lu, Wan-Jung

    2017-07-12

    Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2-10 μM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2-PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.

  20. Advances of stem cell based-therapeutic approaches for tendon repair

    Directory of Open Access Journals (Sweden)

    Lidi Liu

    2017-04-01

    The translational potential of this article: This paper reviews recent progress on stem cell-based therapeutic approaches for tendon repair, which highlights its translational potential and challenges.

  1. 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

  2. Left ventricular mass: Myxoma or thrombus?

    Directory of Open Access Journals (Sweden)

    Monish S Raut

    2015-01-01

    Full Text Available Patient with embolic episode should always be evaluated for cardiac mass. Mass in left ventricular can be a myxoma or thrombus even in a normal functioning heart . In either case, mobile mass with embolic potential should be surgically resected.

  3. Submitral Left Ventricular Aneurysm Associated with Thrombus

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... She was given drugs for management of heart failure and ... treatment abroad. KEYWORDS: Ethiopia, heart failure, submitral aneurysm, thrombus. INTRODUCTION. Submitral left ventricle aneurysm is a rare cardiovascular disorder worldwide, but ... grade 2 pulmonary edema, and bilateral pleural effusion.

  4. Left Ventricular Thrombus among patients undergoing Transthoracic ...

    African Journals Online (AJOL)

    Objective: Left Ventricular Thrombus (LVT) is a well recognized complication of various cardiac conditions, particularly following an acute anterior myocardial infarction and in those with systolic congestive heart failure. Transthoracic echocardiography (TTE) remains the most common imaging modality to make the diagnosis ...

  5. siRNA Genome Screening Approaches to Therapeutic Drug Repositioning

    OpenAIRE

    Ralph A. Tripp; S. Mark Tompkins; Olivia Perwitasari; Abhijeet Bakre

    2013-01-01

    Bridging high-throughput screening (HTS) with RNA interference (RNAi) has allowed for rapid discovery of the molecular basis of many diseases, and identification of potential pathways for developing safe and effective treatments. These features have identified new host gene targets for existing drugs paving the pathway for therapeutic drug repositioning. Using RNAi to discover and help validate new drug targets has also provided a means to filter and prioritize promising therapeutics. This re...

  6. Left Atrial Thrombus Causing Stroke and Syncope: Does Size Matters?

    Directory of Open Access Journals (Sweden)

    Surender Deora

    2014-01-01

    Full Text Available Left atrium thrombus is seen in patients with rheumatic heart disease, severe mitral stenosis and/or atrial fibrillation, but is usually immobile and located in left atrial appendage. Freely mobile thrombus is rarely seen, and the size may vary from few millimeters to centimeters. The clinical presentation varies from presyncope or syncope in a small well organized thrombus to transient ischemic attacks or stroke in large poorly organized thrombus. Management includes urgent surgical removal of thrombus with underlying valvular correction and anticoagulation.

  7. Detection of left atrial thrombus by intracardiac echocardiography in patients undergoing ablation of atrial fibrillation.

    Science.gov (United States)

    Sriram, Chenni S; Banchs, Javier E; Moukabary, Talal; Moradkhan, Raman; Gonzalez, Mario D

    2015-09-01

    The role of intracardiac echocardiography (ICE) to detect thrombus within left atrium (LA) before atrial fibrillation (AF) ablation despite a recent transesophageal echocardiogram (TEE) is not well defined. We examined the prevalence of LA/left atrial appendage (LAA) thrombus using ICE immediately prior to AF ablation in patients in whom anticoagulation was not withheld. We analyzed 122 consecutive patients (62.6 ± 10.8 years, 90 males, CHA(2)DS(2) -VASc score 2.4 ± 1.5, persistent AF 29.5 %) who underwent an ICE-guided AF ablation 1 day after a negative (n = 120) or inconclusive (n = 2) TEE for LA thrombus. LA was imaged with ICE from the right atrium, coronary sinus, and right ventricular inflow tract (RVIT). ICE and TEE images were compared for LAA area, thrombus, and spontaneous echo contrast (SEC). LAA was adequately visualized in 99 and 100 % of patients with TEE and ICE, respectively. RVIT was the best ICE view for LAA visualization. The LAA 2-D-area measured by TEE was 4.9 ± 0.5 vs. 5 ± 0.5 cm(2) by ICE (P = NS). ICE identified a thrombus in seven patients with a previous negative TEE, leading to cancellation of ablation. It ruled out a thrombus in two patients with an inconclusive TEE. Thrombi were found in the LAA (n = 4), atrial septum (n = 2), and left superior pulmonary vein (n = 1). SEC during TEE was more frequent in patients with thrombus on ICE than those without (85.7 vs. 17.4 %; p = 0.03; positive predictive value 23.1 %, negative predictive value 98.9 %). The results of our staged imaging approach suggest that ICE has a complimentary value in re-screening the LA/LAA for thrombus after a recent negative or equivocal TEE. The presence of SEC during TEE increases the probability of finding a thrombus with ICE, which could potentially be dislodged during catheter manipulation.

  8. 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.

  9. On systems and control approaches to therapeutic gain

    Directory of Open Access Journals (Sweden)

    Jackson Robert C

    2006-04-01

    Full Text Available Abstract Background Mathematical models of cancer relevant processes are being developed at an increasing rate. Conceptual frameworks are needed to support new treatment designs based on such models. Methods A modern control perspective is used to formulate two therapeutic gain strategies. Results Two conceptually distinct therapeutic gain strategies are provided. The first is direct in that its goal is to kill cancer cells more so than normal cells, the second is indirect in that its goal is to achieve implicit therapeutic gains by transferring states of cancer cells of non-curable cases to a target state defined by the cancer cells of curable cases. The direct strategy requires models that connect anti-cancer agents to an endpoint that is modulated by the cause of the cancer and that correlates with cell death. It is an abstraction of a strategy for treating mismatch repair (MMR deficient cancers with iodinated uridine (IUdR; IU-DNA correlates with radiation induced cell killing and MMR modulates the relationship between IUdR and IU-DNA because loss of MMR decreases the removal of IU from the DNA. The second strategy is indirect. It assumes that non-curable patient outcomes will improve if the states of their malignant cells are first transferred toward a state that is similar to that of a curable patient. This strategy is difficult to employ because it requires a model that relates drugs to determinants of differences in patient survival times. It is an abstraction of a strategy for treating BCR-ABL pro-B cell childhood leukemia patients using curable cases as the guides. Conclusion Cancer therapeutic gain problem formulations define the purpose, and thus the scope, of cancer process modeling. Their abstractions facilitate considerations of alternative treatment strategies and support syntheses of learning experiences across different cancers.

  10. Echocardiographic predictors of left atrial appendage thrombus formation.

    Science.gov (United States)

    Ayirala, Srilatha; Kumar, Simi; O'Sullivan, David M; Silverman, David I

    2011-05-01

    Although transesophageal echocardiography is the definitive test for the detection of left atrial (LA) appendage thrombus, transthoracic echocardiography has yet to prove useful for the determination of increased risk for LA appendage thrombus formation. The authors hypothesized that higher LA volume and/or lower left ventricular ejection fraction (LVEF) might prove valuable as markers of increased risk for LA appendage thrombus formation and tested this hypothesis in a consecutive retrospective series of patients with atrial fibrillation undergoing both transthoracic and transesophageal echocardiography. Three hundred thirty-four consecutive patients with atrial fibrillation undergoing transesophageal echocardiography for the detection of LA appendage thrombus were studied. Anticoagulation status, CHADS(2) scores, and echocardiographic parameters were catalogued. The relationship between the presence of LA appendage thrombus and covariates was analyzed using binary logistic regression. LA appendage thrombus was detected in 52 patients (15.6%). A higher CHADS(2) score (odds ratio, 1.45; P LA volume index (odds ratio, 1.02; P = .018), and lower LVEF (odds ratio, 1.02; P = .05) were significant predictors of LA appendage thrombus formation. LA appendage thrombus was not seen in patients with CHADS(2) scores ≤ 1, LVEFs > 55%, and a LA volume indexes LA volume index ≤ 1.5 produced 100% sensitivity for the presence of LA appendage thrombus. The presence of LA appendage thrombus is related to both clinical and echocardiographic variables. Although no single echocardiographic variable discriminated between the presence and absence of LA thrombus, a normal LVEF and normal LA volume index were associated with the absence of LA appendage thrombus formation. For patients with atrial fibrillation with CHADS(2) scores ≤ 1, normal left ventricular systolic function and normal LA volume in combination may be a useful measure for the identification of patients at low risk

  11. Robotic-assisted excision of a left ventricular thrombus.

    Science.gov (United States)

    Lutz, Charles J; Bhamidipati, Castigliano M; Ford, Brant; Swartz, Mike; Hauser, Michael; Kyobe, Moses; Dilip, Karikehalli

    2007-09-01

    : Left ventricular thrombus is a rare entity usually associated with myocardial infarction. The daVinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, Calif) offers excellent visualization of the mitral subvalvular apparatus and should provide an effective means to excise a left ventricular mass. : A 34-year-old man presented to an outside institution with fever of unknown origin and ulcerative colitis. As part of this workup, he underwent a transthoracic echocardiogram and subsequently a transesophageal echocardiogram that showed a 2-cm left ventricular apical pedunculated mass. He was referred to our institution for excision of this ventricular mass. Because of the pedunculated nature of the mass, he was deemed a candidate for a robotic-assisted minimally invasive approach. : The patient underwent successful robotic-assisted excision of a left ventricular mass. Total robotic time was 15 minutes. Pathology revealed that the mass was a left ventricular thrombus. The patient experienced an uneventful recovery and was discharged home in 4 days. : Left ventricular mass excision can be safely performed with the daVinci Surgical System. The daVinci Surgical System offers excellent visualization of the entire left ventricular cavity.

  12. 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.

  13. Cervicogenic headache: pathogenesis, clinical features, diagnosis, therapeutic approaches

    Directory of Open Access Journals (Sweden)

    M V Putilina

    2011-01-01

    Full Text Available The concept of cervicogenic headache (CGH comprises the types of headaches having different origins, which are associated with pathology in the cervical spine and its other structural areas. CGH is induced by diverse pathogenetic mechanisms and has different clinical manifestations so it is referred to different classification categories. The anatomic and pathophysiological causes of CGH, its clinical picture, and therapeutic principles are discussed. In clinical practice, more and more preference has been recently given to combined analgesics, ketorolac and nimesulide in particular.

  14. 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.

  15. ROS-modulated therapeutic approaches in cancer treatment.

    Science.gov (United States)

    Raza, Muhammad Hassan; Siraj, Sami; Arshad, Abida; Waheed, Usman; Aldakheel, Fahad; Alduraywish, Shatha; Arshad, Muhammad

    2017-09-01

    Reactive oxygen species (ROS) are produced in cancer cells as a result of increased metabolic rate, dysfunction of mitochondria, elevated cell signaling, expression of oncogenes and increased peroxisome activities. Certain level of ROS is required by cancer cells, above or below which lead to cytotoxicity in cancer cells. This biochemical aspect can be exploited to develop novel therapeutic agents to preferentially and selectively target cancer cells. We searched various electronic databases including PubMed, Web of Science, and Google Scholar for peer-reviewed english-language articles. Selected articles ranging from research papers, clinical studies, and review articles on the ROS production in living systems, its role in cancer development and cancer treatment, and the role of microbiota in ROS-dependent cancer therapy were analyzed. This review highlights oxidative stress in tumors, underlying mechanisms of different relationships of ROS and cancer cells, different ROS-mediated therapeutic strategies and the emerging role of microbiota in cancer therapy. Cancer cells exhibit increased ROS stress and disturbed redox homeostasis which lead to ROS adaptations. ROS-dependent anticancer therapies including ROS scavenging anticancer therapy and ROS boosting anticancer therapy have shown promising results in vitro as well as in vivo. In addition, response to cancer therapy is modulated by the human microbiota which plays a critical role in systemic body functions.

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

    Science.gov (United States)

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

    2016-01-19

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

  17. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.

    Science.gov (United States)

    Berner, Andre K; Kleinman, Mark E

    2016-01-01

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

  18. 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.

  19. 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.

  20. 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

  1. [A new therapeutical approach in neurology (author's transl)].

    Science.gov (United States)

    Divisia, A; Girard-Madoux, M

    The therapeutic action of Tiapridal appeared to the authors particularly precious and constant in delirium tremens, senile agitation and turbulence, whatever the origin, and bucco-linguo-facial dyskinesia, whether the latter were linked to age or whether they formed part of a neuroleptic syndrome. Their experience does not permit them to have any opinion concerning the use of this drug in tremor and chorea, the patients seem to respond favourably to treatment but in an erratic manner. On the other hand the drug was totally inefficacious in patients suffering from spasmodic torticollis and writer's cramp. Finally, it seemed to them useful to emphasise the improvement in comfort in patients suffering from various pains when given Tiapridal. This justifies the place given to Tiapridal among drugs necessary for the daily practice of neurology.

  2. 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.

  3. [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.

  4. 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.

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

    Science.gov (United States)

    Menciotti, Giulio; Borgarelli, Michele

    2017-09-26

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Counselling Refugee Young People: An Exploration of Therapeutic Approaches

    Science.gov (United States)

    Warr, Sally

    2010-01-01

    This paper presents and discusses the key findings from a study that considered significant issues that affect refugees and asylum-seekers, and explored beneficial counselling approaches relevant to this group. In-depth narrative interviews were conducted with three counsellors and three specialist children's support advisors. Data were analysed…

  11. Thrombus age is ideally measured by history or MRV prior to thrombus removal

    DEFF Research Database (Denmark)

    Bækgaard, N; Foegh, P; Wittens, C H A

    2015-01-01

    Many factors are known to be important in order to achieve optimal results after thrombus removal for iliofemoral DVT. Not much is published in the literature about timing the treatment, though many guidelines recommend treatment within 14 days. This time span lies within the phrase of acute DVT ...

  12. Ocular Effects of Sulfur Mustard and Therapeutic Approaches.

    Science.gov (United States)

    Panahi, Yunes; Rajaee, Seyyed Mahdi; Sahebkar, Amirhossein

    2017-11-01

    Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes, and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis, and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication, and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD), and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation, and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin β4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin, and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. J. Cell. Biochem. 118: 3549-3560, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. 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.

  14. 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.

  15. Incidence of thromboembolism following detection by trans-oesophageal echocardiography of left atrial thrombus

    Directory of Open Access Journals (Sweden)

    Ciara Mahon

    2015-09-01

    Conclusion: This is the only study to date that has looked at the incidence of ischemic stroke following a confirmed LAA thrombus, LA thrombus or pre-thrombus state. This single centre study found low stroke rates over a six month follow-up period in patients with a confirmed LAA thrombus, LA thrombus or pre-thrombus state and optimization of OAC. Larger studies would be required to confirm these findings.

  16. Targeting folate metabolism for therapeutic option: A bioinformatics approach.

    Science.gov (United States)

    Hande, Sneha; Goswami, Kalyan; Sharma, Richa; Bhoj, Priyanka; Jena, Lingaraj; Reddy, Maryada Venkata Rami

    2015-11-01

    Lymphatic filariasis, commonly called elephantiasis, poses a burden of estimated level of 5.09 million disability adjusted life year. Limitations of its sole drug, diethylcarbamazine (DEC) drive exploration of effective filarial target. A few plant extracts having polyphenolic ingredients and some synthetic compounds possess potential dihydrofolate reductase (DHFR) inhibitory effect. Here, we postulated a plausible link between folates and polyphenolics based on their common precursor in shikimate metabolism. Considering its implication in structural resemblance based antagonism, we have attempted to validate parasitic DHFR protein as a target. The bioinformatics approach, in the absence of crystal structure of the proposed target, used to authenticate and for virtual docking with suitable tested compounds, showed remarkably lower thermodynamic parameters as opposed to the positive control. A comparative docking analysis between human and Brugia malayi DHFR also showed effective binding parameters with lower inhibition constants of these ligands with parasitic target, but not with human counterpart highlighting safety and efficacy. This study suggests that DHFR could be a valid drug target for lymphatic filariasis, and further reveal that bioinformatics may be an effective tool in reverse pharmacological approach for drug design.

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

    Directory of Open Access Journals (Sweden)

    Aspris Andreas

    2010-05-01

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

  18. Alternative Therapeutic Approach in the Treatment of Oral Pyogenic Granuloma

    Directory of Open Access Journals (Sweden)

    Amr Bugshan

    2015-11-01

    Full Text Available Pyogenic granulomas (PGs in the oral cavity present as an inflammatory hyperplasia usually caused by trauma, hormonal imbalance, chronic irritation, or as the response to a wide variety of drugs. PGs with atypical presentation and behavior may clinically mimic malignant tumors. Thus, histological examination is required to rule out cancer development. Lesions in the oral cavity have been described to be either an isolated entity or present in multiple forms and with multiple recurrences. Conservative surgical excision is the standard choice of treatment in almost every scenario. However, the severity of the lesions and the affected sites often challenge surgical treatment. In this report, we describe the clinical scenario of a recurrent PG, where surgical excision of the lesion was questioned. As an alternative, we describe a noninvasive approach with lesional steroid injections.

  19. Insulinoma After Bariatric Surgery: Diagnostic Dilemma and Therapeutic Approaches.

    Science.gov (United States)

    Mulla, Christopher M; Storino, Alessandra; Yee, Eric U; Lautz, David; Sawnhey, Mandeep S; Moser, A James; Patti, Mary-Elizabeth

    2016-04-01

    Hypoglycemia is increasingly recognized as a complication of bariatric surgery. Typically, hypoglycemia does not appear immediately postoperatively, but rather more than 1 year later, and usually occurs 1-3 h after meals. While rare, insulinoma has been reported after bariatric surgery. Clinical factors which should raise suspicion for insulinoma and the need for comprehensive clinical and biochemical evaluation include hypoglycemia occurring in the fasting state, predating bariatric surgery, and/or worsening immediately postoperatively, and lack of response to conservative therapy. Localization and successful resection of insulinoma can be achieved using novel endoscopic ultrasound and surgical approaches. In summary, hypoglycemia presenting shortly after gastric bypass or with a dominant fasting pattern should be fully evaluated to exclude insulinoma. Additionally, evaluation prior to gastric bypass should include screening for history of hypoglycemia symptoms.

  20. Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device

    Directory of Open Access Journals (Sweden)

    Christopher Tennuci

    2011-01-01

    Full Text Available Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA. Methods. An occlusive thrombus (lamb's blood was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg. Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n=26, thrombus aspiration via the GP thrombus aspiration device (GPTAD (n=30, and mechanical thrombectomy via the Solitaire Device (n=30. Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%. Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD than with the Solitaire (197 SD 64 s P<.05 Kruksal-Wallis. Clot fragmentation was the same in the Solitaire (23% and the GPTAD (23%, but higher with the 4F (53%, P<.05. Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmed in vivo.

  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. [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.

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

    Science.gov (United States)

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

    2017-10-01

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

  4. 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

  5. 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.

  6. 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.

  7. Endovascular Therapeutic Approaches for Acute Superior Mesenteric Artery Occlusion

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  9. Nicorandil prevents sirolimus-induced production of reactive oxygen species, endothelial dysfunction, and thrombus formation

    Directory of Open Access Journals (Sweden)

    Ken Aizawa

    2015-03-01

    Full Text Available Sirolimus (SRL is widely used to prevent restenosis after percutaneous coronary intervention. However, its beneficial effect is hampered by complications of thrombosis. Several studies imply that reactive oxygen species (ROS play a critical role in endothelial dysfunction and thrombus formation. The present study investigated the protective effect of nicorandil (NIC, an anti-angina agent, on SRL-associated thrombosis. In human coronary artery endothelial cells (HCAECs, SRL stimulated ROS production, which was prevented by co-treatment with NIC. The preventive effect of NIC on ROS was abolished by 5-hydroxydecanoate but not by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. NIC also inhibited SRL-induced up-regulation of NADPH oxidase subunit p22phox mRNA. Co-treatment with NIC and SRL significantly up-regulated superoxide dismutase 2. NIC treatment significantly improved SRL-induced decrease in viability of HCAECs. The functional relevance of the preventive effects of NIC on SRL-induced ROS production and impairment of endothelial viability was investigated in a mouse model of thrombosis. Pretreatment with NIC inhibited the SRL-induced acceleration of FeCl3-initiated thrombus formation and ROS production in the testicular arteries of mice. In conclusion, NIC prevented SRL-induced thrombus formation, presumably due to the reduction of ROS and to endothelial protection. The therapeutic efficacy of NIC could represent an additional option in the prevention of SRL-related thrombosis.

  10. Important surgical considerations in the management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus.

    Science.gov (United States)

    Lawindy, Samuel M; Kurian, Tony; Kim, Timothy; Mangar, Devanand; Armstrong, Paul A; Alsina, Angel E; Sheffield, Cedric; Sexton, Wade J; Spiess, Philippe E

    2012-10-01

    What's known on the subject? and What does the study add? Historically, the surgical management of renal tumours with intravascular tumour thrombus has been associated with high morbidity and mortality. In addition, few cases are treated, and typically at tertiary care referral centres, hence little is known and published about the ideal surgical management of such complex cases. The present comprehensive review details how a multidisciplinary surgical approach to renal tumours with intravascular tumour thrombus can optimise patient outcomes. Similarly, we have developed a treatment algorithm in this review that can be used in the surgical planning of such cases. To detail the perioperative and technical considerations essential to the surgical management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus, as historically patients with RCC and IVC tumour thrombus have had an adverse clinical outcome. • Recent surgical and perioperative advances have for the most part optimized the clinical outcome of such patients. A comprehensive review of the scientific literature was conducted using MEDLINE from 1990 to present using as the keywords 'renal cell carcinoma' and 'IVC tumor thrombus'. • In all, 62 manuscripts were reviewed, 58 of which were in English. Of these, 25 peer-reviewed articles were deemed of scientific merit and were assessed in detail as part of this comprehensive review. • These articles consist of medium to large (≥25 patients) peer-reviewed studies containing contemporary data pertaining to the surgical management of RCC and IVC tumour thrombus. • Many of these studies highlight important surgical techniques and considerations in the management of such patients and report on their respective clinical outcomes. Careful preoperative planning is essential to optimising the outcomes within this patient cohort. High quality and detailed preoperative imaging studies help delineate the proximal extension of the IVC tumour

  11. An unexpected complication of acute pancreatitis: Intra-cardiac thrombus.

    Science.gov (United States)

    Keskin, Muhammed; Gümüşdağ, Ayça; Börklü, Edibe Betül; Dayı, Şennur Ünal; Avcı, İlhan İlker; Güvenç, Tolga Sinan; Güngör, Barış; Karabay, Can Yücel; Kozan, Ömer

    2017-05-01

    Left atrial thrombus after acute pancreatitis (AP) is a rare clinical statement. Because of induction of systemic prothrombotic process by AP; some patients with underlying risk factors may develop an intra-cardiac thrombus. We present a 53years-old-woman with moderate mitral stenosis and atrial fibrillation. However the patient was under warfarin treatment, she developed a big left atrial big thrombus which was originated from left atrial appendage after she was suffered from AP. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 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.

  13. Categorization of aortic aneurysm thrombus morphology by magnetic resonance imaging

    DEFF Research Database (Denmark)

    de la Motte, Louise; Pedersen, Mads Møller; Thomsen, Carsten

    2013-01-01

    Magnetic resonance imaging (MRI) has been proposed for qualitative categorization of intraluminal thrombus morphology. We aimed to correlate the qualitative MRI categorization previously described to quantitative measurements of signal intensity and to compare morphological characteristics...

  14. Idiopathic Thrombus in the Common Carotid Artery on Digital Subtraction Angiography

    Directory of Open Access Journals (Sweden)

    Anand Alurkar

    2012-01-01

    Full Text Available In the present study, we discuss the accuracy of digital subtraction angiography (DSA in diagnosis of thrombus in the common carotid artery and its role in the medical management of this disorder. Between 2006 and 2011, four patients (age group ranging from 26 to 48 years presented to our institution with symptoms of stroke. DSA in all these patients showed cigar-shaped filling defect in the common carotid artery. All the patients were managed successfully with anticoagulation treatment. Follow-up Duplex scan was done in all the patients. DSA is the gold standard to diagnose free floating thrombus in the common carotid artery. Medical management can be effective in these patients but a multidisciplinary team approach is needed for appropriate management.

  15. 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.

  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. She will give birth easily: therapeutic approaches to childbirth in 1st millennium BCE cuneiform sources.

    Science.gov (United States)

    Couto-Ferreira M Erica

    2014-01-01

    This article offers, in the first place, an overview on women's healthcare in relation to childbirth in ancient Mesopotamia, as an introduction that helps to evaluate the meaning of the 7th century Assur text BAM 248 within therapeutic cuneiform texts on childbirth. We proceed to analyse the variety of therapeutic approaches to childbirth present in BAM 248, which brings together various healing devices to help a woman give birth quickly and safely. We analyse the text in its entirety as an example of intersection between different medical approaches to childbirth, given the number of differences in the complexity of remedies, in the materia medica employed, in the methods of preparation and application, even in the technical knowledge required and also, most probably, in the social origin and/or use of the remedies in question.

  19. What is the best therapeutic approach to methicillin-resistant Staphylococcus aureus pneumonia?

    Science.gov (United States)

    Peyrani, Paula; Ramirez, Julio

    2015-04-01

    The purpose of this review is to define what the best therapeutic approach is for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Although two meta-analyses reported conflicting findings, recent retrospective studies reported higher success rates in patients with MRSA pneumonia treated with linezolid when compared to vancomycin. Only registration trials are available for some anti-MRSA antibiotics, such as telavancin, ceftaroline, and ceftobiprole. Scarce information is available regarding the best therapeutic approach for MRSA community-acquired pneumonia. Linezolid seems to be a better choice than vancomycin for the treatment of MRSA ventilator-associated pneumonia. It is still unclear whether this affirmation holds for other forms of MRSA pneumonia. Further research is needed to define whether newer antibiotics are better alternatives than currently recommended agents.

  20. Resurfacing total hip replacement–a therapeutical approach in postmenopausal women with osteoporosis and hip arthrosis

    OpenAIRE

    Popescu, D; Ene, R; Cirstoiu, C

    2011-01-01

    Aim: 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 intervention is contraindicated, given the poor quality of osteoporotic bones. We assessed the efficacy of the antiosteoporotic pharmacological therapy to improve bone quality and bone strength in postmenopausal women diagnosed with hip arthrosis and osteoporosis thus facilitating the hip s...

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  2. Study of 99Tcm-annexin V distribution in inferior vena cava thrombus models of rabbits

    International Nuclear Information System (INIS)

    Wu Dayong; Zhang Wenyan; Bian Yanzhu; Hu Yujing

    2013-01-01

    To study 99 Tc m -Annexin V distribution in inferior vena cava thrombus models of rabbits and uptake of 99 Tc m -Annexin V in fresh and old venous thrombus. Rabbits (n=15) were randomly grouped into 3 groups (the fresh thrombus group, old thrombus group, and control group). The rabbits of two thrombus groups developed inferior vena cava thrombus models by operations. The control group received sham operation. The fresh thrombus group and control group rabbits were injected 99 Tc m -Annexin V after operating 1 d; the old thrombus group 14 d. After 1 h all rabbits were killed by injecting overdose pentobarbital sodium. The thrombus (or the inferior vena cava about 3 cm below inferior pole of right kidney level in the control group rabbits), blood, thrombus area inferior vena cava, head lateral inferior vena cava (except the control group), thigh muscle, stomach, myocardium, pulmonary, liver, kidney, spleen, bone and small intestine were obtained from all group rabbits. The ex tissue and blood were weighed and measured by a Well-type detector. The percentage of the injected dose per gram of ex tissue (or blood) was calculated by the above data. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and thigh muscle ratios were calculated by percentage of the injected dose per gram of ex tissue (or blood). The test was used to compare the fresh thrombus group and old thrombus group by SPSS 17.0. The percentage of' the injected dose per gram of thrombi (0.01894± 0.002 16% ID/g) in the fresh thrombus group was higher than the old thrombus group (0.00473±0.001 28% ID/g), P<0.05. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and muscle ratios (3.42±1.06, 26.32±13.60, 31.23 ±16.00, 111.62±52.23) in the fresh thrombus group were higher than the old thrombus group (0.98±0.09, 5.12±2.01, 6.25±2.38, 21.82±5.93), P<0.05 for all. All the thrombi of the fresh thrombus group were confirmed

  3. Hepatic vein tumor thrombus as a risk factor for excessive pulmonary deposition of microspheres during TheraSphere therapy for unresectable hepatocellular carcinoma.

    Science.gov (United States)

    Fleming, Chad J; Andrews, James C; Wiseman, Gregory A; Gansen, Denise N; Roberts, Lewis R

    2009-11-01

    To evaluate the impact of identifiable hepatic vein tumor thrombus on the ability to safely deliver TheraSphere (yttrium 90-containing glass microspheres) for the treatment of hepatocellular carcinoma (HCC). A retrospective review was performed of 87 patients (71 men, 16 women; mean age, 64.5 years; age range, 25-83 y) referred for TheraSphere therapy for HCC during a 2-year period between April 2005 and May 2007. Evaluation included contrast-enhanced computed tomography or magnetic resonance imaging, selective mesenteric angiography, and radionuclide perfusion scintigraphy to measure the arteriovenous shunting through the tumor. Of the 87 patients, 83 underwent angiography and perfusion scintigraphy; 53 were ultimately treated with 65 glass microsphere infusions. Twelve of 83 were identified as having tumor thrombus in a hepatic vein or extending into the inferior vena cava. The mean lung shunt for the patients with hepatic vein tumor thrombus was 30% (range, 11%-60%), compared with 8.2% (range, 3%-23%) for patients without identifiable tumor thrombus. Two of the 12 patients were treated with reduced doses of glass microspheres, and the remaining 10 were offered alternative therapies. The presence of hepatic vein tumor thrombus is a risk factor for an increased lung shunt that may prohibit delivery of a therapeutic dose of TheraSphere to hepatic tumor.

  4. Contemporary management of symptomatic primary aortic mural thrombus.

    Science.gov (United States)

    Verma, Himanshu; Meda, Narendranadh; Vora, Simit; George, Robbie K; Tripathi, Ramesh K

    2014-12-01

    Primary aortic mural thrombus (PAMT) is an uncommon condition but an important source of noncardiogenic emboli with a difficult diagnosis and a high rate of complications, including high mortality. We report our experience of thromboembolic disease from PAMT and review its contemporary management. Retrospective analysis of prospectively collected data of all patients who presented with acute occlusion of a limb or visceral vessels between January 2011 and September 2013 was performed. A total of 88 patients presented with acute occlusion of the extremities or visceral arteries. All underwent extensive evaluation for the possible source of the embolism. Of these 88 patients, 19 patients (mean age, 41.2 years; male:female ratio, 1:2.1) were found to have aortic mural thrombus as the source of distal embolism. Thrombus was located in the thoracic aorta in 10 patients, in the perivisceral aorta in three patients, and in the infrarenal aorta in six patients. Thrombus in the thoracic aorta was treated with stent grafts in four patients, bare metal stents in three patients, and anticoagulation alone in two patients. In the suprarenal abdominal aorta, all three patients underwent trapdoor aortic thrombectomy. Infrarenal aortic thrombus was managed by aortobifemoral embolectomy in two patients, aortic stenting in two patients, surgical thrombectomy in one patient, and anticoagulation alone in one patient. Successful treatment, defined as freedom from further embolic events or recurrence of thrombus, was achieved in 14 of 19 patients (76.4%) with a mean follow-up period of 16.2 months (range, 2-28 months). There were four (21%) thrombus-related deaths, all due to primary thromboembolic insults. One patient needed a below-knee amputation because of a recurrent thrombotic episode. Symptomatic PAMT is an uncommon but important source of noncardiogenic embolus. It appears to occur more frequently in young women. Endovascular coverage of the aortic thrombus, when feasible

  5. 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.

  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. 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

    2017-05-03

    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.

  8. 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.

  9. Right ventricular thrombus: a rare complication of ovarian hyperstimulation syndrome.

    Science.gov (United States)

    Zamirian, Mahmood; Moaref, Ali Reza; Alavi, Seyed Hosein; Zarrabi, Khalil

    2012-12-01

    A 22 years old lady was admitted because of progressive dyspnea, severe abdominal protrusion and lower extremity edema. She had undergone ovarian hyperstimulation for primary infertility by Clomiphen and Human chorionic gonadotropin for 3 months. Abdominopelvic ultrasonography revealed bilateral enlarged multi cystic ovaries and massive ascites. Transesophageal echocardiography revealed a large thrombus in right ventrice apex. Spiral chest CT scan showed normal pulmonary vasculature with no evidence of pulmonary thromboembolism. Heparin was started and repeat echocardiographic study showed gradual disappearance of right ventricular thrombus. Human chorionic gonadotropin is the most important substance which leads to capillary leakage and fluid accumulation in third space. Fluid shift and hypovolemia may cause hypotension, hemoconcentration and formation of vascular thrombus.

  10. Right Ventricular Thrombus: A Rare Complication of Ovarian Hyperstimulation Syndrome

    Directory of Open Access Journals (Sweden)

    Mahmood Zamirian

    2012-12-01

    Full Text Available A 22 years old lady was admitted because of progressive dyspnea, severe abdominal protrusion and lower extremity edema. She had undergone ovarian hyperstimulation for primary infertility by Clomiphen and Human chorionic gonadotropin for 3 months. Abdominopelvic ultrasonography revealed bilateral enlarged multi cystic ovaries and massive ascites. Transesophageal echocardiography revealed a large thrombus in right ventrice apex. Spiral chest CT scan showed normal pulmonary vasculature with no evidence of pulmonary thromboembolism. Heparin was started and repeat echocardiographic study showed gradual disappearance of right ventricular thrombus. Human chorionic gonadotropin is the most important substance which leads to capillary leakage and fluid accumulation in third space. Fluid shift and hypovolemia may cause hypotension, hemoconcentration and formation of vascular thrombus.

  11. Oncolytic Reactivation of KSHV as a Therapeutic Approach for Primary Effusion Lymphoma.

    Science.gov (United States)

    Zhou, Feng; Shimoda, Michiko; Olney, Laura; Lyu, Yuanzhi; Tran, Khiem; Jiang, Guochun; Nakano, Kazushi; Davis, Ryan R; Tepper, Clifford G; Maverakis, Emanual; Campbell, Mel; Li, Yuanpei; Dandekar, Satya; Izumiya, Yoshihiro

    2017-11-01

    Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Currently, treatment options for patients with PEL are limited. Oncolytic viruses have been engineered as anticancer agents and have recently shown increased therapeutic promise. Similarly, lytic activation of endogenous viruses from latently infected tumor cells can also be applied as a cancer therapy. In theory, such a therapeutic strategy would induce oncolysis by viral replication, while simultaneously stimulating an immune response to viral lytic cycle antigens. We examined the combination of the FDA-approved drug ingenol-3-angelate (PEP005) with epigenetic drugs as a rational therapeutic approach for KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal (BET) protein inhibitor, in combination with PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL6 production from PEL cells. Using the dosages of these agents that were found to be effective in reactivating HIV (as a means to clear latent virus with highly active antiretroviral therapy), we were able to inhibit PEL growth in vitro and delay tumor growth in a PEL xenograft tumor model. KSHV reactivation was mediated by activation of the NF-κB pathway by PEP005, which led to increased occupancy of RNA polymerase II onto the KSHV genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. Thus, combination of PEP005 with a BET inhibitor may be considered as a rational therapeutic approach for the treatment of PEL. Mol Cancer Ther; 16(11); 2627-38. ©2017 AACR . ©2017 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    Franca Patrizi

    2006-01-01

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

  14. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    NARCIS (Netherlands)

    Santos, Emilie M. M.; Yoo, Albert J.; Beenen, Ludo F.; Berkhemer, Olvert A.; den Blanken, Mark D.; Wismans, Carrie; Niessen, Wiro J.; Majoie, Charles B.; Marquering, Henk A.; Fransen, Puck S. S.; Beumer, Debbie; van den Berg, Lucie A.; Lingsma, Hester F.; Schonewille, Wouter J.; Vos, Jan Albert; Nederkoorn, Paul J.; Wermer, Marieke J. H.; van Walderveen, Marianne A. A.; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A.; Lycklama à Nijeholt, Geert J.; Boiten, Jelis; Brouwer, Patrick A.; Emmer, Bart J.; de Bruijn, Sebastiaan F.; van Dijk, Lukas C.; Kappelle, L. Jaap; Lo, Rob H.; van Dijk, Ewoud J.; de Vries, Joost; de Kort, Paul L. M.; van den Berg, Jan S. P.; A A M van Hasselt, Boudewijn; Aerden, Leo A. M.; Dallinga, René J.; Visser, Marieke C.; Bot, Joseph C. J.; Vroomen, Patrick C.; Eshghi, Omid; Schreuder, Tobien H. C. M. L.; Heijboer, Roel J. J.; Keizer, Koos; Tielbeek, Alexander V.; Hertog, Heleen M. Den; Gerrits, Dick G.; van den Berg-Vos, Renske M.; Karas, Giorgos B.; Steyerberg, Ewout W.; Flach, H. Zwenneke; Sprengers, Marieke E. S.; Jenniskens, Sjoerd F. M.; van den Berg, René; Koudstaal, Peter J.; van Zwam, Wim H.; Roos, Yvo B. W. E. M.; van der Lugt, Aad; van Oostenbrugge, Robert J.; Dippel, Diederik W. J.

    2016-01-01

    Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert

  15. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    NARCIS (Netherlands)

    E.M.M. Santos (Emilie M.); A.J. Yoo (Albert J.); L.F.M. Beenen (Ludo); O.A. Berkhemer (Olvert); M.D. Den Blanken (Mark D.); C. Wismans (Carrie); W.J. Niessen (Wiro); C.B. Majoie (Charles); H. Marquering (Henk)

    2016-01-01

    textabstractIntroduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by

  16. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    NARCIS (Netherlands)

    Santos, E.M.; Yoo, A.J.; Beenen, L.F.; Berkhemer, O.A.; Blanken, M.D. den; Wismans, C.; Niessen, W.J.; Majoie, C.B.; Marquering, H.A.; Dijk, E.J. van; et al.,

    2016-01-01

    INTRODUCTION: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and

  17. 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.

  18. 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.

  19. Thrombus overlying the main stem crista: a three dimensional reconstruction.

    NARCIS (Netherlands)

    G.J.J. van Langenhove (Glenn); P. Vermeersch (Paul); P.W.J.C. Serruys (Patrick)

    2001-01-01

    textabstractA 67 year old patient was referred to our hospital for diagnostic catheterisation. For six days she had been suffering from unstable angina, which was stabilised medically. She had no coronary risk factors. The diagnostic angiogram showed a large thrombus reaching from the first diagonal

  20. Metastatic Adenocarcinoma Presenting as Extensive Cavoatrial Tumor Thrombus

    Science.gov (United States)

    Johari, Bushra; Abdul Aziz, Yang Faridah; Krishnasamy, Sivakumar; Looi, Lai Meng; Hashim, Shahrul Amry; Raja Mokhtar, Raja Amin

    2015-01-01

    The presence of tumor thrombus in the right atrium is frequently the result of direct intraluminal extension of infra-diaphragmatic malignancy into the inferior vena cava (IVC) or supradiaphragmatic carcinoma into the superior vena cava (SVC). Right atrial tumor thrombus with extension into both SVC and IVC has not been reported in the literature. We present a patient who presented with symptoms of right atrial and SVC obstruction. Imaging revealed presence of a thrombus in the right atrium, extending to the SVC and IVC, with the additional findings of a left adrenal mass and multiple liver lesions. The histopathological examination of the right atrial mass revealed metastatic adenocarcinoma cells. The patient was given a presumptive diagnosis of metastatic adenocarcinoma, most likely adrenal in origin, with multiple hepatic lesions suspicious for metastasis. The clinical outcome of the patient was not favorable; the patient succumbed before the adrenal mass could be confirmed to be the primary tumor. This case highlights that in patients manifesting with extensive cavoatrial thrombus as, the existence of primary carcinoma should be considered especially in the adrenal cortex or in the lung. PMID:26060549

  1. Anatomic Characteristics and Clinical Implications of Angiographic Coronary Thrombus

    NARCIS (Netherlands)

    C.A.M. Campos (Carlos); F. Costa (Francesco); H.M. Garcia-Garcia (Hector); C.V. Bourantas (Christos); P. Suwannasom (Pannipa); M. Valgimigli (Marco); M-A.M. Morel (Marie-Angèle); S.W. Windecker (Stephan); P.W.J.C. Serruys (Patrick)

    2015-01-01

    textabstractBackground - The distribution of thrombus-containing lesions (TCLs) in an all-comer population admitted with a heterogeneous clinical presentation (stable, ustable angina, or an acute coronary syndrome) and treated with percutaneous coronary intervention is yet unclear, and the long-term

  2. Oncolytic adenoviruses as a therapeutic approach for osteosarcoma: A new hope

    Directory of Open Access Journals (Sweden)

    Marc Garcia-Moure

    2017-11-01

    Full Text Available Osteosarcoma is the most common bone cancer among those with non-hematological origin and affects mainly pediatric patients. In the last 50 years, refinements in surgical procedures, as well as the introduction of aggressive neoadjuvant and adjuvant chemotherapeutic cocktails, have increased to nearly 70% the survival rate of these patients. Despite the initial therapeutic progress the fight against osteosarcoma has not substantially improved during the last three decades, and almost 30% of the patients do not respond or recur after the standard treatment. For this group there is an urgent need to implement new therapeutic approaches. Oncolytic adenoviruses are conditionally replicative viruses engineered to selectively replicate in and kill tumor cells, while remaining quiescent in healthy cells. In the last years there have been multiple preclinical and clinical studies using these viruses as therapeutic agents in the treatment of a broad range of cancers, including osteosarcoma. In this review, we summarize some of the most relevant published literature about the use of oncolytic adenoviruses to treat human osteosarcoma tumors in subcutaneous, orthotopic and metastatic mouse models. In conclusion, up to date the preclinical studies with oncolytic adenoviruses have demonstrated that are safe and efficacious against local and metastatic osteosarcoma. Knowledge arising from phase I/II clinical trials with oncolytic adenoviruses in other tumors have shown the potential of viruses to awake the patient´s own immune system generating a response against the tumor. Generating osteosarcoma immune-competent adenoviruses friendly models will allow to better understand this potential. Future clinical trials with oncolytic adenoviruses for osteosarcoma tumors are warranted. Keywords: Oncolytic adenovirus, Virotherapy, Osteosarcoma, Bones, Cancer, Tumor

  3. 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.

  4. 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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arie Budovsky

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Ionica Floriana Elvira

    2015-09-01

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

  8. Substrate deprivation: a new therapeutic approach for the glycosphingolipid lysosomal storage diseases.

    Science.gov (United States)

    Platt, F M; Butters, T D

    2000-02-01

    The glycosphingolipid (GSL) lysosomal storage diseases are a family of human metabolic diseases that, in their severest forms, cause death in early infancy, as a result of progressive neurodegeneration. They are caused by mutations in the genes encoding the glycohydrolases or the activator proteins that catabolise GSLs within lysosomes. In these diseases the GSL substrate of the defective enzyme accumulates in the lysosome, where it is stored and leads to cellular dysfunction and disease. The therapeutic options for treating these diseases are relatively limited; in fact, there are currently no available therapies for most of these disorders. The problem is further compounded by difficulties in delivering therapeutic agents to the central nervous system, which is where the pathology is frequently manifested. To date, research effort has mainly focused on strategies for augmenting enzyme concentrations to compensate for the underlying defect. These strategies include bone-marrow transplantation, enzyme-replacement therapy and gene therapy. Our group has been exploring the alternative strategy of substrate deprivation. This approach aims to balance the rate of GSL synthesis with the impaired rate of GSL breakdown. Studies using an asymptomatic mouse model of Tay-Sachs disease have shown that substrate deprivation prevents GSL storage. In a severe neurodegenerative mouse model of Sandhoff disease, substrate deprivation delayed the onset of symptoms and disease progression, and significantly increased life expectancy. The implications of this research for human therapy have been discussed.

  9. 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.

  10. Unraveling new therapeutic targets of coronary artery disease by genetic approaches.

    Science.gov (United States)

    Lee, Sang Eun; Kim, Hyo-Soo

    2015-01-01

    Coronary artery disease (CAD) is the most common cause of death and physical disabilities in developed countries, even though efforts to identify and target causal factors such as hypertension and dyslipidemia have brought tremendous improvements in prevention and treatment. A rapid advance in technology has unraveled new genetic variants associated with CAD and also provided great opportunities to identify novel pathogenic mechanisms and to develop new drugs with higher specificity. Whole-genome sequencing and whole-exome sequencing has made it possible to find rare alleles that are responsible for CAD in small, affected families and case-control studies in a very efficient manner. At present, genome-wide association studies have identified more than 50 loci that explain approximately 10% of the heritability of CAD, most of which is unrelated to traditional risk factors. Mendelian randomization studies enable identification of causal factors among numerous biomarkers and to narrow down promising therapeutic targets. This review highlights new genetic approaches and demonstrates the extent to which the outcome contributes to the finding of new therapeutic targets.

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

    Directory of Open Access Journals (Sweden)

    Antignani PL

    2013-03-01

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

  12. Novel therapeutic approaches for the treatment of castration-resistant prostate cancer.

    Science.gov (United States)

    Heidegger, Isabel; Massoner, Petra; Eder, Iris E; Pircher, Andreas; Pichler, Renate; Aigner, Friedrich; Bektic, Jasmin; Horninger, Wolfgang; Klocker, Helmut

    2013-11-01

    Prostate cancer is a leading cause of cancer death in men in developed countries. Once the tumor has achieved a castration-refractory metastatic stage, treatment options are limited with the average survival of patients ranging from two to three years only. Recently, new drugs for treatment of castration-resistant prostate cancer (CRPC) have been approved, and others are in an advanced stage of clinical testing. In this review we provide an overview of the new therapeutic agents that arrived in the clinical praxis or are tested in clinical studies and their mode of action including hormone synthesis inhibitors, new androgen receptor blockers, bone targeting and antiangiogenic agents, endothelin receptor antagonists, growth factor inhibitors, novel radiotherapeutics and taxanes, and immunotherapeutic approaches. Results and limitations from clinical studies as well as future needs for improvement of CRPC treatments are critically discussed. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

  15. Parallel artificial liquid membrane extraction of psychoactive analytes: a novel approach in therapeutic drug monitoring.

    Science.gov (United States)

    Olsen, Katharina Norgren; Ask, Kristine Skoglund; Pedersen-Bjergaard, Stig; Gjelstad, Astrid

    2018-03-01

    Liquid-liquid extraction is widely used in therapeutic drug monitoring of antipsychotics, but difficulties in automation of the technique can result in long operational time. In this paper, parallel artificial liquid membrane extraction was used for extraction of serotonin- and serotonin-norepinephrine reuptake inhibitors from human plasma, and an approach to automate the technique was investigated. Eight model analytes were extracted from 125 μl human plasma with recoveries in the range 72-111% (relative standard deviation [RSD] ≤12.8%). A semiautomated pipettor was successfully utilized in the procedure, reducing the manual handling time. Real patient samples were analyzed with satisfying accuracy. A semiautomated extraction of serotonin-and serotonin-norepinephrine reuptake inhibitors by parallel artificial liquid membrane extraction extraction was successfully performed.

  16. Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease

    Directory of Open Access Journals (Sweden)

    João Antonio Chaves de Souza

    2012-04-01

    Full Text Available Recently, new treatment approaches have been developed to target the host component of periodontal disease. This review aims at providing updated information on host-modulating therapies, focusing on treatment strategies for inhibiting signal transduction pathways involved in inflammation. Pharmacological inhibitors of MAPK, NFκB and JAK/STAT pathways are being developed to manage rheumatoid arthritis, periodontal disease and other inflammatory diseases. Through these agents, inflammatory mediators can be inhibited at cell signaling level, interfering on transcription factors activation and inflammatory gene expression. Although these drugs offer great potential to modulate host response, their main limitations are lack of specificity and developments of side effects. After overcoming these limitations, adjunctive host modulating drugs will provide new therapeutic strategies for periodontal treatment.

  17. 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

  18. Pediatric minor head trauma: do cranial CT scans change the therapeutic approach?

    Directory of Open Access Journals (Sweden)

    Felipe P. Andrade

    Full Text Available OBJECTIVES: 1 To verify clinical signs correlated with appropriate cranial computed tomography scan indications and changes in the therapeutic approach in pediatric minor head trauma scenarios. 2 To estimate the radiation exposure of computed tomography scans with low dose protocols in the context of trauma and the additional associated risk. METHODS: Investigators reviewed the medical records of all children with minor head trauma, which was defined as a Glasgow coma scale ≥13 at the time of admission to the emergency room, who underwent computed tomography scans during the years of 2013 and 2014. A change in the therapeutic approach was defined as a neurosurgical intervention performed within 30 days, hospitalization, >12 hours of observation, or neuro-specialist evaluation. RESULTS: Of the 1006 children evaluated, 101 showed some abnormality on head computed tomography scans, including 49 who were hospitalized, 16 who remained under observation and 36 who were dismissed. No patient underwent neurosurgery. No statistically significant relationship was observed between patient age, time between trauma and admission, or signs/symptoms related to trauma and abnormal imaging results. A statistically significant relationship between abnormal image results and a fall higher than 1.0 meter was observed (p=0.044. The mean effective dose was 2.0 mSv (0.1 to 6.8 mSv, corresponding to an estimated additional cancer risk of 0.05%. CONCLUSION: A computed tomography scan after minor head injury in pediatric patients did not show clinically relevant abnormalities that could lead to neurosurgical indications. Patients who fell more than 1.0 m were more likely to have changes in imaging tests, although these changes did not require neurosurgical intervention; therefore, the use of computed tomography scans may be questioned in this group. The results support the trend of more careful indications for cranial computed tomography scans for children with minor

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

    Directory of Open Access Journals (Sweden)

    Syed Babar Jamal

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

  20. Thrombus composition in sudden cardiac death from acute myocardial infarction.

    Science.gov (United States)

    Silvain, Johanne; Collet, Jean-Philippe; Guedeney, Paul; Varenne, Olivier; Nagaswami, Chandrasekaran; Maupain, Carole; Empana, Jean-Philippe; Boulanger, Chantal; Tafflet, Muriel; Manzo-Silberman, Stephane; Kerneis, Mathieu; Brugier, Delphine; Vignolles, Nicolas; Weisel, John W; Jouven, Xavier; Montalescot, Gilles; Spaulding, Christian

    2017-04-01

    It was hypothesized that the pattern of coronary occlusion (thrombus composition) might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD) in myocardial infarction (MI). The TIDE (Thrombus and Inflammation in sudden DEath) study included patients with angiographically-proven acute coronary occlusion as the cause of a ST elevation MI (STEMI) complicated by Sudden Cardiac Death (SCD group) or not (STEMI group). Thrombi were obtained by thrombo-aspiration before primary percutaneous coronary stenting and analyzed with a quantitative method using scanning electron microscopy. We compared the composition of the thrombi responsible for the coronary occlusion between the two groups and evaluated factors influencing its composition. We included 121 patients and found that thrombus composition was not different between the SCD group (n=23) and the STEMI group (n=98) regarding content of fibrin fibers (60.3±18.4% vs. 62.4±18.4% respectively, p=0.68), platelets (16.3±19.2% vs. 15.616.7±%, p=0.76), erythrocytes (14.6±12.5% vs. 13±12.1%, p=0.73) and leukocytes (0.6±0.9% vs. 0.8±1.5%, p=0.93). Thrombus composition did not differ between patients receiving upstream-use of glycoprotein IIb/IIIa platelet receptor inhibitors (GPI) and patients free of GPI. The only factor found to influence thrombus composition was the ischemic time from symptom onset to primary PCI, with a decreased content in fibrin fibers (57.8±18.5% vs. 71.9±10.1%, p=0.0008) and a higher platelet content (19.2±19.1% vs. 7.9±5.7% p=0.014) in early presenters (6h of ischemic time). Composition of intracoronary thrombi in STEMI patients does not differ between those presenting with and without SCD. Time from symptom onset to coronary reperfusion seems to be the strongest factor influencing thrombus composition in MI. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-08-01

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

  2. A multimodality vascular imaging phantom of an abdominal aortic aneurysm with a visible thrombus

    Energy Technology Data Exchange (ETDEWEB)

    Allard, Louise; Chayer, Boris; Qin Zhao [Laboratory of Biorheology and Medical Ultrasonics, Research Center, University of Montreal Hospital (CRCHUM), Quebec H2L 2W5 (Canada); Soulez, Gilles [Department of Radiology, University of Montreal Hospital (CHUM), Quebec H2L 2M1 (Canada); Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Quebec H3T 1J4 (Canada); Institute of Biomedical Engineering, University of Montreal, Quebec H3T 1J4 (Canada); Roy, David [Institute of Biomedical Engineering, University of Montreal, Quebec H3T 1J4 (Canada); Cloutier, Guy [Laboratory of Biorheology and Medical Ultrasonics, Research Center, University of Montreal Hospital (CRCHUM), Quebec H2L 2W5 (Canada); Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Quebec H3T 1J4 (Canada); Institute of Biomedical Engineering, University of Montreal, Quebec H3T 1J4 (Canada)

    2013-06-15

    Purpose: With the continuous development of new stent grafts and implantation techniques, it has now become technically feasible to treat abdominal aortic aneurysms (AAA) with challenging anatomy using endovascular repair with standard, fenestrated, or branched stent-grafts. In vitro experimentations are very useful to improve stent-graft design and conformability or imaging guidance for stent-graft delivery or follow-up. Vascular replicas also help to better understand the limitation of endovascular approaches in challenging anatomy and possibly improve surgical planning or training by practicing high risk clinical procedures in the laboratory to improve outcomes in the operating room. Most AAA phantoms available have a very basic anatomy, which is not representative of the clinical reality. This paper presents a method of fabrication of a realistic AAA phantom with a visible thrombus, as well as some mechanical properties characterizing such phantom. Methods: A realistic AAA geometry replica of a real patient anatomy taken from a multidetector computed tomography (CT) scan was manufactured. To demonstrate the multimodality imaging capability of this new phantom with a thrombus visible in magnetic resonance (MR) angiography, CT angiography (CTA), digital subtraction angiography (DSA), and ultrasound, image acquisitions with all these modalities were performed by using standard clinical protocols. Potential use of this phantom for stent deployment was also tested. A rheometer allowed defining hyperelastic and viscoelastic properties of phantom materials. Results: MR imaging measurements of SNR and CNR values on T1 and T2-weighted sequences and MR angiography indicated reasonable agreement with published values of AAA thrombus and abdominal components in vivo. X-ray absorption also lay within normal ranges of AAA patients and was representative of findings observed on CTA, fluoroscopy, and DSA. Ultrasound propagation speeds for developed materials were also in

  3. Open removal of a retained retrohepatic inferior vena cava filter with a residual primary neuroectodermal renal tumoral thrombus.

    Science.gov (United States)

    Hinojosa, Carlos A; Torres-Machorro, Adriana; Lizola, Rene; Anaya-Ayala, Javier E

    2015-10-29

    Primary neuroectodermal renal tumours (PNET) are rare and aggressive neoplasms; thrombosis of the inferior vena cava (IVC) is associated with this entity. We report here the case of a 19-year-old man who experienced a new onset of abdominal pain. A CT scan revealed a large left renal mass, perirenal haematoma and IVC thrombosis. Owing to an acute drop in haemoglobin and subsegmentary pulmonary embolism, he underwent emergency selective renal artery angiography and embolisation of bleeding vessels and IVC filter (IVCF) placement. Once stable, he underwent a left radical nephrectomy and IVC thrombectomy; the pathology report confirmed PNET. 6 months later, imaging revealed a residual tumoral thrombus in the IVCF located in the retrohepatic IVC. The patient underwent removal of this device and the thrombus via a right thoracoabdominal approach. He recovered well and at 4 months, he continues his chemotherapy cycles. 2015 BMJ Publishing Group Ltd.

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

    Science.gov (United States)

    Scheen, A J; Paquot, N

    2011-04-01

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

  5. Clinical and radiographic features of sarcoidosis in menopausal women: The impact on therapeutic approach and prognosis

    Directory of Open Access Journals (Sweden)

    Milošković Vladana R.

    2010-01-01

    Full Text Available Background/Aim. Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The aim of the study was to determine are there significant differences in clinical manifestations, radiographic and lung function findings and therapeutic approach in menopausal female sarcoidosis patients compared to premenopausal ones. Methods. Seventy seven Caucasian women (average age 43.71 years, range 38- 54 with sarcoidosis diagnosed at the University Hospital from January to October 2006, were included in the study. They were divided into two groups according to their menstrual period status. The group I included 42 women with normal menstrual cycle, while the group II included 35 menopausal women (either spontaneous or after hysterectomy. The patients were not under hormonal therapy. Results. We found significantly higher proportion of the first radiographic stage (66.7% vs 34.2%, p < 0.05 and acute form of sarcoidosis (57.2% vs 17.1%; p < 0.01 in the group I in relation to the group II. Extrapulmonary sarcoidosis was more frequent in the group II than in the group I (p < 0.01. Disturbances of lung ventilation were registered in 50.8% of all the patients, and decrease of one or both of diffusion parameters was found in 63.6%, but without significant differences between the groups (p > 0.05. Hypercalciuria was found in 19.1% of the patients in the group I and 42.8% of the patient in the group II (p < 0.05. A difference in the therapy approach was also found to be significant with methotrexate more frequently applied in the group II than in the group I (p < 0.01. Conclusion. Menopausal women with sarcoidosis may represent a group of patients that requires special attention in diagnostic procedure, therapeutic approach and follow-up, to prevent unfavourable course of the disease. Attention should be particularly focused on the detection of extrapulmonary sites involvement in this group of the patients. Further prospective studies are needed to reveal

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

    Science.gov (United States)

    2017-01-01

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

  7. Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

    Science.gov (United States)

    Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

    2016-09-01

    It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

  8. 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. PMID:27242528

  9. Transjugular intrahepatic portosystemic shunt for the treatment of portal vein thrombus:its current status

    International Nuclear Information System (INIS)

    Qi Xingshun; Han Guohong; Fan Daiming

    2010-01-01

    The prevalence of portal vein thrombosis in the general population is about 1.1%, while it is about 10%-25% in the cirrhotic patients. The severe clinical complication in patients with acute portal vein thrombosis is ischemic intestinal infarction when the thrombus extends to the mesenteric venous arch. The complications include bleeding due to gastroesophageal varices, ascites and deterioration of live function in the patients with chronic portal vein thrombosis. The recently-published Practice Guidelines indicate that the treatment of portal vein thrombosis includes anticoagulation,thrombolysis, transjugular intrahepatic portosystemic shunt (TIPS) and surgical thrombectomy. TIPS has some advantages in treating portal vein thrombus. It can directly and effectively re-canalize the occluded portal vein. Moreover, it can accelerate portal flow and prevent recurrent thrombosis after the shunt is well-established. The disadvantages of TIPS include technical difficulties and potential complications. However, percutaneous transhepatic, transsplenic and transmesenteric approaches well facilitate the TIPS procedure. Additionally, preoperative evaluation of portal vein anatomy can provide a safe and effective choice in treating patients with portal cavernoua caver who are going to receive TIPS. Nevertheless, in the absence of relevant prospective studies, the application of TIPS for the management of portal vein thrombosis is still limited. (authors)

  10. 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.

  11. Cognitive and brain reserve for mind-body therapeutic approaches in multiple sclerosis: a review.

    Science.gov (United States)

    Crescentini, Cristiano; Urgesi, Cosimo; Fabbro, Franco; Eleopra, Roberto

    2014-01-01

    Cognitive impairment is one of the most disabling symptoms of multiple sclerosis (MS), affecting a large proportion of patients and having a severe impact on their quality of life. Nevertheless, there exists a large variability in the neuropsychological profiles of MS patients and some of them appear to withstand better than others the MS-related brain pathology before showing cognitive decline. In recent years, many studies have made use of concepts such as cognitive reserve and brain reserve to take account of the inter-individual discrepancy between cognitive impairment and MS pathology. Critically, these studies have left open the fundamental issue of the clinical implications of this research for the treatment of cognitive dysfunction in MS. We provide an updated and extensive overview of the studies that have explored cognitive and brain reserve in MS and discuss their implications for non-pharmacological therapeutic strategies aimed at potentiating patients' reserve. In particular, the possible utility of integrated approaches based on mind-body techniques such as mindfulness-meditation is considered. We conclude that these techniques represent challenging mental enriching activities that may help cultivating cognitive reserve and more systematic research on their efficacy to protect against cognitive degradation in MS is encouraged.

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Miguel Gus

    1999-03-01

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

  15. 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.

  16. 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

  17. Resurfacing total hip replacement–a therapeutical approach in postmenopausal women with osteoporosis and hip arthrosis

    Science.gov (United States)

    Popescu, D; Ene, R

    2011-01-01

    Aim: 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 intervention is contraindicated, given the poor quality of osteoporotic bones. We assessed the efficacy of the antiosteoporotic pharmacological therapy to improve bone quality and bone strength in postmenopausal women diagnosed with hip arthrosis and osteoporosis thus facilitating the hip surgical intervention. Methods: We evaluated 20 postmenopausal women aged between 53–60 years diagnosed with osteoporosis according to the WHO criteria, by using dual–energy X–ray absorptiometry (DXA) for bone mineral density measurements. All these patients had low hip T score (osteopenia/ osteoporosis) and also incipient hip arthrosis. The surgical approach was delayed for 12 months and all the patients received bisphosphonate therapy with calcium and vitamin D supplements. DXA scans were performed after 12 months of therapy in all the patients. Results: A surgical intervention with resurfacing total hip replacement was performed in 12 of the 16 patients presenting with increasing BMD, 4 of them showing elements of rapidly advancing hip arthrosis to a stage that made this type of intervention impossible. We chose not to use this technique in the group with stable BMD (4 patients). All 12 women surgically treated had a favorable post–operative outcome without experiencing a femoral neck fracture during the surgical intervention or during the twelve–month follow–up. All 20 patients continued to receive bisphosphonate therapy. Conclusion: In postmenopausal women with osteoporosis and associated hip arthrosis, improving bone mass and bone quality with bisphosphonate therapy is necessary and important in order to allow hip arthroplasty, by using the technique of resurfacing, avoiding the risk of intra–operative fractures and with a favorable post–operative long

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

    Science.gov (United States)

    Popescu, D; Ene, R; Cirstoiu, C

    2011-05-15

    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 intervention is contraindicated, given the poor quality of osteoporotic bones. We assessed the efficacy of the antiosteoporotic pharmacological therapy to improve bone quality and bone strength in postmenopausal women diagnosed with hip arthrosis and osteoporosis thus facilitating the hip surgical intervention. We evaluated 20 postmenopausal women aged between 53-60 years diagnosed with osteoporosis according to the WHO criteria, by using dual-energy X-ray absorptiometry (DXA) for bone mineral density measurements. All these patients had low hip T score (osteopenia/ osteoporosis) and also incipient hip arthrosis. The surgical approach was delayed for 12 months and all the patients received bisphosphonate therapy with calcium and vitamin D supplements. DXA scans were performed after 12 months of therapy in all the patients. A surgical intervention with resurfacing total hip replacement was performed in 12 of the 16 patients presenting with increasing BMD, 4 of them showing elements of rapidly advancing hip arthrosis to a stage that made this type of intervention impossible. We chose not to use this technique in the group with stable BMD (4 patients). All 12 women surgically treated had a favorable post-operative outcome without experiencing a femoral neck fracture during the surgical intervention or during the twelve-month follow-up. All 20 patients continued to receive bisphosphonate therapy. In postmenopausal women with osteoporosis and associated hip arthrosis, improving bone mass and bone quality with bisphosphonate therapy is necessary and important in order to allow hip arthroplasty, by using the technique of resurfacing, avoiding the risk of intra-operative fractures and with a favorable post-operative long-term outcome.

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

    Science.gov (United States)

    George, Jeffy; Mattapallil, Joseph J

    2018-01-01

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

  20. Recent Inferior Myocardial Infarction Complicated with a Right Ventricular Thrombus Detected by Three Cardiac Imaging Modalities.

    Science.gov (United States)

    Kuno, Toshiki; Imaeda, Syohei; Hashimoto, Kenji; Ryuzaki, Toshinobu; Saito, Tetsuya; Yamazaki, Hiroyuki; Tabei, Ryota; Kodaira, Masaki; Hase, Manabu; Numasawa, Yohei

    2018-03-01

    We report the case of a 71-year-old woman diagnosed with recent inferior myocardial infarction complicated with right ventricular infarction and a right ventricular thrombus. Three-dimensional transthoracic echocardiography, contrast-enhanced computed tomography, and cardiac magnetic resonance imaging clearly detected a thrombus. We consider cases with a recent right ventricular infarction to require assessment for thrombus formations in the right ventricle. Fortunately, vigorous anticoagulation therapy resolved the thrombi in both the right ventricle and right coronary artery.

  1. Associations Between Collateral Status and Thrombus Characteristics and Their Impact in Anterior Circulation Stroke.

    Science.gov (United States)

    Alves, Heitor C; Treurniet, Kilian M; Dutra, Bruna G; Jansen, Ivo G H; Boers, Anna M M; Santos, Emilie M M; Berkhemer, Olvert A; Dippel, Diederik W J; van der Lugt, Aad; van Zwam, Wim H; van Oostenbrugge, Robert J; Lingsma, Hester F; Roos, Yvo B W E M; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

    2018-02-01

    Thrombus characteristics and collateral score are associated with functional outcome in patients with acute ischemic stroke. It has been suggested that they affect each other. The aim of this study is to evaluate the association between clot burden score, thrombus perviousness, and collateral score and to determine whether collateral score influences the association of thrombus characteristics with functional outcome. Patients with baseline thin-slice noncontrast computed tomography and computed tomographic angiography images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included (n=195). Collateral score and clot burden scores were determined on baseline computed tomographic angiography. Thrombus attenuation increase was determined by comparing thrombus density on noncontrast computed tomography and computed tomographic angiography using a semiautomated method. The association of collateral score with clot burden score and thrombus attenuation increase was evaluated with linear regression. Mediation and effect modification analyses were used to assess the influence of collateral score on the association of clot burden score and thrombus attenuation increase with functional outcome. A higher clot burden score (B=0.063; 95% confidence interval, 0.008-0.118) and a higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003-0.026) were associated with higher collateral score. Collateral score mediated the association of clot burden score with functional outcome. The association between thrombus attenuation increase and functional outcome was modified by the collateral score, and this association was stronger in patients with moderate and good collaterals. Patients with lower thrombus burden and higher thrombus perviousness scores had higher collateral score. The positive effect of thrombus perviousness on clinical outcome was only present in patients with

  2. The influence of neck thrombus on clinical outcome and aneurysm morphology after endovascular aneurysm repair

    OpenAIRE

    Bastos Gonçalves, Frederico; Verhagen, Hence; Chinsakchai, Khamin; Keulen, Jasper; Voûte, Michiel; Zandvoort, Herman; Moll, Frans; Herwaarden, Joost

    2012-01-01

    textabstractObjective: This study investigated the influence of significant aneurysm neck thrombus in clinical and morphologic outcomes after endovascular aneurysm repair (EVAR). Methods: The patient population was derived from a prospective EVAR database from two university institutions in The Netherlands from 2004 to 2008. Patients with significant thrombus in the neck (>2 mm in thickness in at least >25% of circumference) were identified as the thrombus group and were compared with the rem...

  3. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Emilie M.M. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, P.O. Box 2040, Rotterdam (Netherlands); Department of Radiology, AMC, Amsterdam (Netherlands); Yoo, Albert J. [Texas Stroke Institute, Plano, TX (United States); Beenen, Ludo F.; Majoie, Charles B. [Department of Radiology, AMC, Amsterdam (Netherlands); Berkhemer, Olvert A. [Department of Radiology, AMC, Amsterdam (Netherlands); Department of Neurology, Erasmus MC, Rotterdam (Netherlands); Blanken, Mark D. den; Wismans, Carrie [AMC, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Niessen, Wiro J. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, P.O. Box 2040, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Marquering, Henk A. [Department of Radiology, AMC, Amsterdam (Netherlands); AMC, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Collaboration: on behalf of the MR CLEAN investigators

    2016-02-15

    Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland-Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs. (orig.)

  4. Thrombus length discrepancy on dual-phase CT can predict clinical outcome in acute ischemic stroke

    International Nuclear Information System (INIS)

    Park, Mina; Kim, Kyung-eun; Lee, Seung-Koo; Shin, Na-Young; Lim, Soo Mee; Song, Dongbeom; Heo, Ji Hoe; Kim, Jin Woo; Oh, Se Won

    2016-01-01

    The thrombus length may be overestimated on early arterial computed tomography angiography (CTA) depending on the collateral status. We evaluated the value of a grading system based on the thrombus length discrepancy on dual-phase CT in outcome prediction. Forty-eight acute ischemic stroke patients with M1 occlusion were included. Dual-phase CT protocol encompassed non-contrast enhanced CT, CTA with a bolus tracking technique, and delayed contrast enhanced CT (CECT) performed 40s after contrast injection. The thrombus length discrepancy between CTA and CECT was graded by using a three-point scale: G0 = no difference; G1 = no difference in thrombus length, but in attenuation distal to thrombus; G2 = difference in thrombus length. Univariate and multivariate analyses were performed to define independent predictors of poor clinical outcome at 3 months. The thrombus discrepancy grade showed significant linear relationships with both the collateral status (P = 0.008) and the presence of antegrade flow on DSA (P = 0.010) with good interobserver agreement (κ = 0.868). In a multivariate model, the presence of thrombus length discrepancy (G2) was an independent predictor of poor clinical outcome [odds ratio = 11.474 (1.350-97.547); P =0.025]. The presence of thrombus length discrepancy on dual-phase CT may be a useful predictor of unfavourable clinical outcome in acute M1 occlusion patients. (orig.)

  5. Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

    International Nuclear Information System (INIS)

    Santos, Emilie M.M.; Yoo, Albert J.; Beenen, Ludo F.; Majoie, Charles B.; Berkhemer, Olvert A.; Blanken, Mark D. den; Wismans, Carrie; Niessen, Wiro J.; Marquering, Henk A.

    2016-01-01

    Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland-Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Abdullah Özçelik

    2018-02-01

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

  7. Outcomes and cost comparison of three therapeutic approaches to allergic rhinitis.

    Science.gov (United States)

    Fairchild, Carol J; Durden, Emily; Cao, Zhun; Smale, Patrick

    2011-01-01

    Allergic rhinitis (AR) is a global health problem because of its increasing impact on economics, society, and the individual's quality of life. This study compares the outcomes and cost of three intranasal therapeutic approaches to the treatment of AR. This was a retrospective cohort study using propensity scores to achieve balanced cohorts. The study population included patients ≥16 years of age with at least one intranasal prescription claim, without concurrent nasal polyps or sinusitis. Health care use and costs, airway infections, pharmacy costs, and indicators of unsatisfactory treatment (i.e., treatment augmentation or switching) were evaluated in the 1-year follow-up period using a claims database. Data from 141,190 patients in intranasal antihistamines (INA) therapy, intranasal steroids (INS) therapy, and intranasal combination therapy (ICT) cohorts were analyzed. The INA cohort showed the lowest rate of change in treatment (switching or augmentation). Switching rates were lowest in the INS therapy cohort, whereas augmentation was lowest in the INA cohort. AR- and asthma-related medication costs were significantly lower in the INA cohort. No differences were observed in airway infections and overall health care costs. Concurrent chronic obstructive pulmonary disorder and asthma were the strongest predictors of health care cost and respiratory infection in the follow-up period. A change in treatment was noted in ∼⅓ of the entire study population. None of the treatments had a remarkable effect on health care costs or the occurrence of airway infections. The INA treatment cohort had lower AR- and asthma-related medication costs.

  8. The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach.

    Science.gov (United States)

    Salahuddin, Parveen; Rabbani, Gulam; Khan, Rizwan Hasan

    2014-09-01

    Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies have shown that glycation induces the formation of the β-sheet structure in β-amyloid protein, α-synuclein, transthyretin (TTR), copper-zinc superoxide dismutase 1 (Cu, Zn-SOD-1), and prion protein. Aggregation of the β-sheet structure in each case creates fibrillar structures, respectively causing Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, and prion disease. It has been suggested that oligomeric species of glycated α-synuclein and prion are more toxic than fibrils. This review focuses on the pathway of AGE formation, the synthesis of different types of AGE, and the molecular mechanisms by which glycation causes various types of neurodegenerative disease. It discusses several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic and naturally occurring inhibitors. Modulation of the AGE-RAGE axis is now considered promising in the prevention of neurodegenerative diseases. Additionally, the review covers several defense enzymes and proteins in the human body that are important anti-glycating systems acting to prevent the development of neurodegenerative diseases.

  9. 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 

  10. 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.

  11. 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

  12. 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

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

    Czech Academy of Sciences Publication Activity Database

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

    2017-01-01

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

  14. Compressive mechanical properties of the intraluminal thrombus in abdominal aortic aneurysms and fibrin-based thrombus mimics

    Science.gov (United States)

    Ashton, John H.; Vande Geest, Jonathan P.; Simon, Bruce R.; Haskett, Darren G.

    2010-01-01

    An intraluminal thrombus (ILT) forms in the majority of abdominal aortic aneurysms (AAAs). While the ILT has traditionally been perceived as a byproduct of aneurysmal disease, the mechanical environment within the ILT may contribute to the degeneration of the aortic wall by affecting biological events of cells embedded within the ILT. In this study, the drained secant modulus (E5 ∼ modulus at 5% strain) of ILT specimens (luminal, medial, and abluminal) procured from elective open repair was measured and compared using unconfined compression. Five groups of fibrin-based thrombus mimics were also synthesized by mixing various combinations of fibrinogen, thrombin, and calcium. Drained secant moduli were compared to determine the effect of the components' concentrations on mimic stiffness. The stiffness of the mimics was also compared to the native ILT. Preliminary data on the water content of the ILT layers and mimics was measured. It was found that the abluminal layer (E5 = 19.3 kPa) is stiffer than the medial (2.49 kPa) and luminal (1.54 kPa) layers, both of which are statistically similar. E5 of the mimics (0.63, 0.22, 0.23, 0.87, and 2.54 kPa) is dependent on the concentration of all three components: E5 decreases with a decrease in fibrinogen (60 to 20 and 20 to 15 mg/ml) and a decrease in thrombin (3 to 0.3 units/ml), and E5 increases with a decrease in calcium (0.1 to 0.01 M). E5 from two of the mimics were not statistically different than the medial and luminal layers of ILT. A thrombus mimic with similar biochemical components, structure, and mechanical properties as native ILT would provide an appropriate test medium for AAA mechanobiology studies. PMID:19058807

  15. 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.

  16. 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)

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

    International Nuclear Information System (INIS)

    Diez Cabezas, B.

    2015-01-01

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

  18. Research progress of interventional therapy in primary hepatic carcinoma companied with portal vein tumor thrombus

    International Nuclear Information System (INIS)

    Qiu Guoqin; Luo Pengfei; Chen Yuqiang

    2011-01-01

    Portal vein tumor thrombus is an important factor on the prognosis of hepatic carcinoma. Interventional therapy is one of the effective therapies and plays an important role in the clinical treatment because of the advantage of minimally invasive and repeatable. The research and progress of interventional therapy on portal vein tumor thrombus was reviewed in this article. (authors)

  19. Variable effects of radiological contrast media on thrombus growth in a rabbit jugular vein thrombosis model

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Biemond, B. J.; Sturk, A.; Hoek, J.; ten Cate, J. W.

    1991-01-01

    We studied the effect of an ionic high osmolar contrast medium (Ioxitalamate), an ionic low osmolar contrast medium (Ioxaglate) and various nonionic low osmolar contrast media (Iopamidol, Iopromide and Iohexol) on thrombus growth in a rabbit jugular vein thrombosis model. Thrombus growth was

  20. Successful catheter directed thrombolysis of IVC and renal vein occlusive thrombus.

    LENUS (Irish Health Repository)

    McCarthy, E

    2011-11-01

    Thrombus formation is a recognised complication of IVC filter placement, however IVC and bilateral renal vein occlusion secondary to thrombus is much less common. We present a case of infrahepatic caval and bilateral renal vein occlusion secondary to thrombosis of a suprarenal IVC filter. With progressive clinical deterioration and failure of conservative medical management the patient underwent successful mechanical disruption and catheter directed thrombolysis.

  1. Examination of venous tumor thrombus with colorectal cancer by enhanced CT

    International Nuclear Information System (INIS)

    Sato, Osamu; Kiba, Maki; Tazoe, Jun

    2010-01-01

    Recently, multi detector row CT (MDCT) has been largely used and enabled to detect drainage vessels of tumors. Then we tried examining the ratio, by using enhanced CT, of the cases that has venous tumor thrombus with colorectal cancer, and found the 3 cases out of 176 to be venous tumor thrombus of mesenteric veins in advanced stage. (author)

  2. Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging

    NARCIS (Netherlands)

    Delewi, Ronak; Nijveldt, Robin; Hirsch, Alexander; Marcu, Constantin B.; Robbers, Lourens; Hassell, Marriela E. C. J.; de Bruin, Rianne H. A.; Vleugels, Jim; van der Laan, Anja M.; Bouma, Berto J.; Tio, René A.; Tijssen, Jan G. P.; van Rossum, Albert C.; Zijlstra, Felix; Piek, Jan J.

    2012-01-01

    Introduction: Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic

  3. Tumor thrombus formation in two dogs with insulinomas.

    Science.gov (United States)

    Hambrook, Lydia E; Kudnig, Simon T

    2012-10-15

    A 9-year-old sexually intact male Staffordshire Bull Terrier and a 9-year-old neutered male Boxer were evaluated for intermittent neurologic signs including muscle tremors, ataxia, episodic collapse, disorientation, and seizures. Both dogs had low blood glucose and high serum insulin concentrations. Results of abdominal ultrasonography were unremarkable for both dogs. Exploratory laparotomy revealed a mass that extended from the body of the pancreas into the pancreaticoduodenal vein in each dog. Marginal resection of pancreatic masses was performed, and tumor thrombi were removed via venotomy in both dogs. Histologic evaluation indicated the masses were pancreatic islet cell tumors with tumor thrombi. Clinical signs resolved following surgical resection of tumors and tumor thrombi, and the dogs were euglycemic during the follow-up period (17 and 45 months after surgery). Although gross tumor thrombus formation has been identified in humans with insulinomas, tumor thrombi have not been previously reported for dogs with insulinomas. Surgical removal of tumor thrombi via venotomy seemed to be well tolerated by the dogs. Tumor thrombus formation did not seem to adversely affect prognosis for the 2 dogs of this report.

  4. 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.

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

    Science.gov (United States)

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

    2016-07-01

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

  6. How are we improving the delivery to back of the eye? Advances and challenges of novel therapeutic approaches.

    Science.gov (United States)

    Agrahari, Vibhuti; Agrahari, Vivek; Mandal, Abhirup; Pal, Dhananjay; Mitra, Ashim K

    2017-10-01

    Drug delivery to the back of the eye requires strategic approaches that guarantee the long-term therapeutic effect with patient compliance. Current treatments for posterior eye diseases suffer from significant challenges including frequent intraocular injections of anti-VEGF agents and related adverse effects in addition to the high cost of the therapy. Areas covered: Treatment challenges and promising drug delivery approaches for posterior segment eye diseases, such as age-related macular degeneration (AMD) are summarized. Advances in the development of several nanotechnology-based systems, including stimuli-responsive approaches to enhance drug bioavailability and overcome existing barriers for effective ocular delivery are discussed. Stem cell transplantation and encapsulated cell technology (ECT) approaches to treat posterior eye diseases are elaborated. Expert opinion: There are several drug delivery systems demonstrating promising results. However, a better understanding of ocular barriers, disease pathophysiology, and drug clearance mechanisms is required for better therapeutic outcomes. The stem cell transplantation strategy and ECT approach provide positive results in AMD therapy, but there are a number of challenges that must be overcome for long-term efficiency. Ultimately, there are numerous multidimensional challenges to cure vision problems and a collaborative approach among scientists is required.

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

    OpenAIRE

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

    2015-01-01

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

  8. 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.

  9. 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. 

  10. 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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

    Buzinde, Christine N; Yarnal, Careen

    2012-03-01

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

  13. A fuzzy approach to evaluation and management of therapeutic procedure in diabetes mellitus treatment

    Directory of Open Access Journals (Sweden)

    Tadić Danijela

    2010-01-01

    Full Text Available In this paper a new fuzzy model (FMOTPD2 is developed and by this model the measures of beliefs are determined so that one of the groups of possible therapeutic procedures is optimal for each patient of type 2 diabetes on hospital treatment. The choice of therapeutic procedure on individual level, which is one of the demands of modern medicine, means that each therapeutic procedure is to be evaluated by multiple and different criteria. In this paper, evaluation criteria are classified into two groups: (1 common criteria by which medicines used by the type 2 diabetes patients are being evaluated and (2 specific criteria, by which the patients' 1h state of health with type 2 diabetes mellitus is being estimated. Generally, the relative importance and values of these criteria are different. It is assumed that (a the relative importance of evaluation criteria is defined by a team of medical experts and described by linguistic expressions and (b the values of evaluation criteria are determined by evidence data, anamnesis and a diagnostic process. They can be crisp or uncertain. The most often used linguistic expressions describing the relative importance of evaluation criteria are modeled by triangular fuzzy numbers. The rest of uncertainties, which exist in developed model are described by discrete fuzzy numbers. A new algorithm for determining a unified fuzzy portrait of treated therapeutic procedures for each patient is given. It enables calculation of the measures of beliefs that some therapeutic procedures are more optimal than the others. The developed model is illustrated by examples with real word data collected in a hospital.

  14. 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.

  15. Albumin based versatile multifunctional nanocarriers for cancer therapy: Fabrication, surface modification, multimodal therapeutics and imaging approaches.

    Science.gov (United States)

    Kudarha, Ritu R; Sawant, Krutika K

    2017-12-01

    Albumin is a versatile protein used as a carrier system for cancer therapeutics. As a carrier it can provide tumor specificity, reduce drug related toxicity, maintain therapeutic concentration of the active moiety like drug, gene, peptide, protein etc. for long period of time and also reduce drug related toxicities. Apart from cancer therapy, it is also utilized in the imaging and multimodal therapy of cancer. This review highlights the important properties, structure and types of albumin based nanocarriers with regards to their use for cancer targeting. It also provides brief discussion on methods of preparation of these nanocarriers and their surface modification. Applications of albumin nanocarriers for cancer therapy, gene delivery, imaging, phototherapy and multimodal therapy have also been discussed. This review also provides brief discussion about albumin based marketed nano formulations and those under clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

    Science.gov (United States)

    Gue, Ying X; Gorog, Diana A

    2017-08-25

    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

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

    Directory of Open Access Journals (Sweden)

    H Michael eShepard

    2015-08-01

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

  18. 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.

  19. Combination radiotherapy for hepatocellular carcinoma with intraductal tumor thrombus: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Tanizaki, Hiroshi E-mail: info@shin-tokyohospital.or.jp; Furuse, Junji; Yoshino, Masahiro; Ogino, Takashi; Ishikura, Satoshi; Satake, Mitsuo; Hasebe, Takahiro

    2001-06-01

    We report the successful treatment of hepatocellular carcinoma (HCC) associated with an intraductal tumor thrombus in a 67-year-old male. Abdominal ultrasonography (US) and computed tomography (CT) revealed intrahepatic biliary dilatation in the left hepatic lobe and an intraductal tumor thrombus. The main tumor lesion was not clearly visualized on abdominal US, dynamic CT, and hepatic angiography. We biopsied the intraductal tumor thrombus under US guidance. Histologically the biopsy specimen was a poorly differentiated HCC We thus diagnosed HCC with intraductal tumor thrombus. The total serum bilirubin level gradually rose to 3.1 mg/dl. This tumor was inoperable because of severe hepatic dysfunction. We chose to treat the patient with radiotherapy aimed only at the intraductal tumor thrombus because the main tumor was unclear. A percutaneous transhepatic biliary drainage (PTBD) tube was inserted into the common bile duct beyond the tumor thrombus and the tube was dilated. Once total serum bilirubin had reached the normal range, a combination of external beam radiation therapy (EBRT) plus an intraluminal brachytherapy, {sup 192}Ir boost was administered. The intraductal tumor thrombus was found to have vanished and the PTBD tube was removed. After this treatment, transcatheter hepatic arterial embolization was performed at the point of tumor appearance. This patient had a relatively long survival, {approx}30 months, with no clinical evidence of recurrent disease and biliary drainage was not necessary.

  20. AIDS-Related Non-Hodgkin’s Lymphoma in Sub-Saharan Africa: Current Status and Realities of Therapeutic Approach

    Science.gov (United States)

    Mwamba, Peter M.; Mwanda, Walter O.; Busakhala, NaftaliW.; Strother, R. Matthew; Loehrer, Patrick J.; Remick, Scot C.

    2013-01-01

    Today AIDS-related non-Hodgkin’s lymphoma (AR-NHL) is a significant cause of morbidity and mortality in HIV-infected patients the world over, and especially in sub-Saharan Africa. While the overall incidence of AR-NHL since the emergence of combination antiretroviral therapy (cART) era has declined, the occurrence of this disease appears to have stabilized. In regions of the world where access to cART is challenging, the impact on disease incidence is less clear. In the resource-rich environment it is clinically well recognized that it is no longer appropriate to consider AR-NHL as a single disease entity and rather treatment of AIDS lymphoma needs to be tailored to lymphoma subtype. While intensive therapeutic strategies in the resource-rich world are clearly improving outcome, in AIDS epicenters of the world and especially in sub-Saharan Africa there is a paucity of data on treatment and outcomes. In fact, only one prospective study of dose-modified oral chemotherapy and limited retrospective studies with sufficient details provide a window into the natural history and clinical management of this disease. The scarcities and challenges of treatment in this setting provide a backdrop to review the current status and realities of the therapeutic approach to AR-NHL in sub-Saharan Africa. More pragmatic and risk-adapted therapeutic approaches are needed. PMID:24205439

  1. [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.

  2. Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Delewi, Ronak [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Interuniversity Cardiology Institute of the Netherlands (Netherlands); Nijveldt, Robin [Department of Cardiology, VU University Medical Center, Amsterdam (Netherlands); Hirsch, Alexander [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Marcu, Constantin B.; Robbers, Lourens [Department of Cardiology, VU University Medical Center, Amsterdam (Netherlands); Hassell, Marriela E.C.J.; Bruin, Rianne H.A. de; Vleugels, Jim; Laan, Anja M. van der; Bouma, Berto J. [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Tio, René A. [Thorax Center, University Medical Center Groningen, Groningen (Netherlands); Tijssen, Jan G.P. [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Rossum, Albert C. van [Department of Cardiology, VU University Medical Center, Amsterdam (Netherlands); Zijlstra, Felix [Thorax Center, Department of Cardiology, Erasmus University Medical Center, Rotterdam (Netherlands); Piek, Jan J., E-mail: j.j.piek@amc.uva.nl [Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2012-12-15

    Introduction: Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI. Methods: 200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events. Results: On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B = 0.02, SE = 0.02, p < 0.001). Routine TTE had a sensitivity of 21–24% and a specificity of 95–98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ = 0.91 and κ = 0.96) compared to TTE (κ = 0.74 and κ = 0.53). Conclusion: LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large.

  3. Thrombus-in-Transit Entrapped in a Partially Ligated Left Atrial Appendage

    Directory of Open Access Journals (Sweden)

    Farideh Roshanali

    2015-10-01

    Full Text Available A 54-year-old man referred to our center with Barlow’s disease and severe mitral regurgitation. He had atrial fibrillation (AF rhythm, with a mildly enlarged left atrium (LA. Transesophageal echocardiography (TEE showed no clot in the LA and LA appendage; there was only mild spontaneous echo contrast in the LA appendage. The patient underwent mitral valve repair and the Maze operation, during which the LA appendage was ligated with the double suture technique. He was discharged from the hospital in good condition and in sinus rhythm. He was recommended Warfarin and PT control.One month later, he returned with the complaint of vision loss twice in the left eye each time for a few seconds. The AF rhythm had returned.TEE demonstrated a fresh and mobile thrombus entrapped in the LA appendage with a small portion in the LA (Figures 1 and 2. Laboratory tests showed therapeutic international normalized ratio (INR. The patient refused re- operation.  Plavix was added to his medication, and he was discharged.

  4. Renal angiomyolipoma with inferior vena caval thrombus in a 32-year-old male

    Directory of Open Access Journals (Sweden)

    Matthew W Christian

    2009-01-01

    Full Text Available Renal angiomyolipoma (AML rarely presents with evidence of extension into the renal vein, inferior vena cava (IVC or atrium. We report a case of a renal AML with a tumor thrombus to the IVC in a 32-year-old male. The patient subsequently underwent a right radical nephrectomy with IVC tumor thrombectomy. To our knowledge, there are four published cases of renal AML presenting with tumor thrombus in males. This case report describes the management of the youngest male ever to develop a renal AML with IVC tumor thrombus.

  5. Surgical treatment of a floating thrombus of the ascending aorta causing repeated arterial embolisms.

    Science.gov (United States)

    Labsaili, Hicham; Bouaggad, Amal; Alami, Aroussi Aziz; Rama, Akhtar; Leprince, Pascal

    2015-07-01

    Floating thrombus of the ascending aorta is a rare and often ignored cause of peripheral embolic events. We report the observation of a patient presenting recurrent peripheral embolic demonstrations: acute ischemia of the right lower limb complicated of a thigh amputation and transient cerebrovascular accident. The assessment by angioscanner highlighted a 40-mm thrombus of the ascending aorta. The thrombus was removed surgically. This diagnosis should not be ignored in the assessment of an embolic pathology with the risk of severe functional after-effects caused by an important diagnostic delay. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. [Randomized Comparison of Two Approaches to Initial Warfarin Dosing: Time in Therapeutic Range of International Normalized Ratio During Hospitalization].

    Science.gov (United States)

    Gordeev, I G; Averkov, O V; Mishchenko, L N; Levchuk, N N; Vechorko, V I

    2017-09-01

    To perform a randomized, open-label comparison of average time in therapeutic range (TTR) of international normalized ratio (INR) using two approaches to initial warfarin dosing during hospitalization: the standard method and the one using individual patient characteristics (clinical algorithm - the studied approach). We randomly assigned 60 patients with different indications for vitamin K antagonist therapy to the studied approach (n=31, intervention group) or to the standard method (n=29, control group). А target INR range for all patients was 2.0 to 3.0. The average TTR and portions of INR values within target range during the whole time of drug dosing turned out to be small. TTR was 22.4% with standard method and 21.4% with clinical algorithm, which was well below desired 60%. The opportunities for achieving target INR in inpatient settings, regardless of warfarin dosing regimen, are limited.

  7. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches.

    Science.gov (United States)

    Boxer, Adam L; Yu, Jin-Tai; Golbe, Lawrence I; Litvan, Irene; Lang, Anthony E; Höglinger, Günter U

    2017-07-01

    Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms that are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future. These criteria also include definitions for variant PSP syndromes with different patterns of movement, language, or behavioural features than have been conclusively associated with PSP pathology. Data from new diagnostic biomarkers can be combined with the clinical features of disease to increase the specificity of the new criteria for underlying PSP pathology. Because PSP is associated with tau protein abnormalities, there is growing interest in clinical trials of new tau-directed therapies. These therapies are hypothesised to have disease-modifying effects by reducing the concentration of toxic forms of tau in the brain or by compensating for loss of tau function. Since tau pathology is also central to Alzheimer's disease and chronic traumatic encephalopathy, a successful tau therapeutic for PSP might inform treatment of other neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Irina Gavrilovskaya

    2012-01-01

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

  10. Roles of glial cells in schizophrenia: possible targets for therapeutic approaches.

    Science.gov (United States)

    Takahashi, Nagahide; Sakurai, Takeshi

    2013-05-01

    Glial cells consisting of oligodendrocytes, astrocytes, microglia, and NG2 positive cells are major cell populations in the central nervous system, number-wise. They function as effectors and modulators of neurodevelopment through a wide variety of neuron-glial cell interactions in brain development and functions. Glial cells can be affected by both genetic and environmental factors, leading to their dysfunctions in supporting neuronal development and functions. These in turn can affect neuronal cells, causing alterations at the circuitry level that manifest as behavioral characteristics associated with schizophrenia in late teens-early twenties. Glial cells are also involved in neuroinflammatory processes, which sometimes have deleterious effects on the normal brain development. If the glial involvement plays significant roles in schizophrenia, the processes involving glial cells can become possible therapeutic targets for schizophrenia. A number of known antipsychotics are shown to have beneficial effects on glial cells, but other drugs targeting glial cell functions may also have therapeutic effects on schizophrenia. The latter can be taken into consideration for future drug development for schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2018-04-04

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

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

    Directory of Open Access Journals (Sweden)

    Salca Amalia

    2015-09-01

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

  13. 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

  14. Therapeutic Significance ofLoligo vulgaris(Lamarck, 1798) ink Extract: A Biomedical Approach.

    Science.gov (United States)

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

    2017-12-01

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

  15. Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds☆

    Science.gov (United States)

    Madigan, Nicolas N.; McMahon, Siobhan; O’Brien, Timothy; Yaszemski, Michael J.; Windebank, Anthony J.

    2010-01-01

    This review highlights current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury. The concept of developing 3-dimensional polymer scaffolds for placement into a spinal cord transection model has recently been more extensively explored as a solution for restoring neurologic function after injury. Given the patient morbidity associated with respiratory compromise, the discrete tracts in the spinal cord conveying innervation for breathing represent an important and achievable therapeutic target. The aim is to derive new neuronal tissue from the surrounding, healthy cord that will be guided by the polymer implant through the injured area to make functional reconnections. A variety of naturally derived and synthetic biomaterial polymers have been developed for placement in the injured spinal cord. Axonal growth is supported by inherent properties of the selected polymer, the architecture of the scaffold, permissive microstructures such as pores, grooves or polymer fibres, and surface modifications to provide improved adherence and growth directionality. Structural support of axonal regeneration is combined with integrated polymeric and cellular delivery systems for therapeutic drugs and for neurotrophic molecules to regionalize growth of specific nerve populations. PMID:19737633

  16. 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.

  17. Liver tumours in children: diagnostic and therapeutic approach in the Tropics

    Directory of Open Access Journals (Sweden)

    Yao Atteby

    2012-12-01

    Full Text Available Liver tumours in children are rare and their prognosis are poor. Through a cross and retrospective study, we examined the epidemiological, clinical and therapeutic aspects on a number of patients in our hospital to try and improve the management of cases. This study involved 66 children admitted to the pediatric oncology unit of University Hospital of Treichville in Abidjan between 1991 and 2007. The average age of children was 7.2 years and the sex ratio of 1.4. 42 children lived in the countryside and 52 children were from disadvantaged areas. 63.2% of children were not vaccinated against hepatitis B. The abdominal mass was the primary sign of discovery and these tumours were dominated in both their primitive and secondary forms by the Burkitt's lymphoma.

  18. Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke

    Directory of Open Access Journals (Sweden)

    Lauren E. Previch

    2016-07-01

    Full Text Available Cerebral edema often manifests after the development of cerebrovascular disease, particularly in the case of stroke, both ischemic and hemorrhagic. Without clinical intervention, the influx of water into brain tissues leads to increased intracranial pressure, cerebral herniation, and ultimately death. Strategies to manage the development of edema constitute a major unmet therapeutic need. However, despite its major clinical significance, the mechanisms underlying cerebral water transport and edema formation remain elusive. Aquaporins (AQPs are a class of water channel proteins which have been implicated in the regulation of water homeostasis and cerebral edema formation, and thus represent a promising target for alleviating stroke-induced cerebral edema. This review examines the significance of relevant AQPs in stroke injury and subsequently explores neuroprotective strategies aimed at modulating AQP expression, with a particular focus on AQP4, the most abundant AQP in the central nervous system.

  19. Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke

    Science.gov (United States)

    Previch, Lauren E.; Ma, Linlin; Wright, Joshua C.; Singh, Sunpreet; Geng, Xiaokun; Ding, Yuchuan

    2016-01-01

    Cerebral edema often manifests after the development of cerebrovascular disease, particularly in the case of stroke, both ischemic and hemorrhagic. Without clinical intervention, the influx of water into brain tissues leads to increased intracranial pressure, cerebral herniation, and ultimately death. Strategies to manage the development of edema constitute a major unmet therapeutic need. However, despite its major clinical significance, the mechanisms underlying cerebral water transport and edema formation remain elusive. Aquaporins (AQPs) are a class of water channel proteins which have been implicated in the regulation of water homeostasis and cerebral edema formation, and thus represent a promising target for alleviating stroke-induced cerebral edema. This review examines the significance of relevant AQPs in stroke injury and subsequently explores neuroprotective strategies aimed at modulating AQP expression, with a particular focus on AQP4, the most abundant AQP in the central nervous system. PMID:27438832

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

    International Nuclear Information System (INIS)

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

    1999-12-01

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

  1. 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.

  2. 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.

  3. Mechanism-Based Therapeutic Approaches to Rhabdomyolysis-Induced Renal Failure

    Science.gov (United States)

    Boutaud, Olivier; Roberts, L. Jackson

    2010-01-01

    Rhabdomyolysis-induced renal failure represents up to 15% of all cases of acute renal failure. Many studies over the past four 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 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 discuss the value of therapeutic interventions aiming at inhibiting myoglobin redox cycling for the treatment of rhabdomyolysis-induced renal failure. PMID:21034813

  4. Intense Microbubbles Mimicking Mobile Thrombus in a Patient with Prosthetic Mitral Valve

    Directory of Open Access Journals (Sweden)

    Fatma Yılmaz Coşkun

    2017-06-01

    Full Text Available Microbubbles have been presumed as gaseous emboli, which originate during mechanical heart valve closure, but are not seen in bioprosthetic valves. In this report, we presented a cluster of microbubbles mimicking mobile thrombus in a patient with mechanical mitral valve prosthesis. A 30-year-old female with a history of implanted mechanical valve at the mitral position underwent a routine examination. She was asymptomatic and her physical examination was unremarkable. Transthoracic echocardiography showed a mobile thrombus-like mass on the ventricular side of the prosthetic mitral valve moving into the left ventricular outflow tract. However, close examination of images indicated that the mass was in fact intense microbubbles mimicking thrombus. Intense mobile microbubbles can be misdiagnosed as a mobile thrombus. We recommend and underscore the importance of detailed echocardiographic examination in case of mobile mass to avoid misdiagnosis in patients with mechanical heart valves.

  5. The influence of neck thrombus on clinical outcome and aneurysm morphology after endovascular aneurysm repair

    NARCIS (Netherlands)

    F.M.V. Bastos Gonçalves (Frederico); H.J.M. Verhagen (Hence); K. Chinsakchai (Khamin); J.W. van Keulen (Jasper); M.T. Voûte (Michiel); H.J.A. Zandvoort (Herman); F.L. Moll (Frans); J.A. van Herwaarden (Joost)

    2012-01-01

    textabstractObjective: This study investigated the influence of significant aneurysm neck thrombus in clinical and morphologic outcomes after endovascular aneurysm repair (EVAR). Methods: The patient population was derived from a prospective EVAR database from two university institutions in The

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Christoph Jindra

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

  8. Characterization of an experimental venous thrombus model with MRI, phlebography and histology

    International Nuclear Information System (INIS)

    Schmitz, S.A.; Schiffler, S.; Gust, R.; Winterhalter, S.; Wolf, K.J.; Coupland, S.E.

    2005-01-01

    Introduction: Several magnetic resonance (MR) techniques designed to demonstrate the characteristic signal intensity of blood degeneration products of thrombi have been suggested, but the effect of thrombus organization on the MR display, in particular with regard to its temporal evolution, remains to be determined. It is the purpose of this study to develop a stagnation thrombus model in rabbits and to characterize thrombus at different ages with two (MR) imaging techniques, phlebography and histology. Materials and Methods: Venous stagnation thrombi were induced in the external jugular veins of rabbits using a minimally invasive radiological technique to produce artificial embolic vascular occlusion and hypercoagulability. Twenty-five animals were divided into 5 groups of 5 animals, and each group underwent 1.5 T MR imaging at 1, 3, 5, 7 and 9 days after thrombus induction using a T1-weighted magnetization-prepared rapid gradient-echo sequence (MP-RAGE: TR 10.4 msec, TE 4.0 msec, FA 15 ) and a T2-weighted fast low-angle shot sequence (FLASH: TR 54 msec, TE 18 msec, FA15 ). The thrombus length was measured on the T1-weighted images. Thrombus conspicuity, signal intensity, and heterogeneity on T2* weighted images were described using visual scales. Radiographic venography and histology served as reference methods. Results: Thrombi were successfully induced in all animals. The overall thrombus length decreased from 43±9 (day 1 after induction) to 23±4 mm (day 9). On 3D-reconstructions of the T1-weighted images, the visible portion of the true thrombus length relative to the overall thrombus length was 0.16±0.3 (day 1), 0.24±0.3 (day 3),0.38±0.5 (day 5), 0.06±0.1 (day 7) and 0.00 (day 9). Sixteen of 25 thrombi were detectable with the T2*-weighted technique. The overall thrombus signal intensity decreased with the age of the thrombus from day 1 to day 9. The histological evaluation showed that the rabbit thrombi closely resemble human thrombi morphologically

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

    Directory of Open Access Journals (Sweden)

    Tania Martins-Marques

    2016-09-01

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

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

    Science.gov (United States)

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

    2010-01-01

    To determine whether there are gender-based differences in the clinical presentation, therapeutic approaches and outcomes in acute poisoning treated with activated charcoal. A descriptive study conducted in the Emergency Department of the Hospital Clínic de Barcelona over the 7 years between the years 2001 and 2008. The study included poisoned patients who had received activated charcoal. The variables included, epidemiological data, clinical and toxicological presentation, therapeutic approach, time in emergency department and outcomes. A total of 575 patients were included in the study. The mean age was 37.8 (SD 14.8) years and 65.7% were females. No differences were observed between males and females with respect to age, number of drugs involved in the poisoning or the number of tablets ingested, but a higher prevalence of benzodiazepine poisoning was observed in females compared to males (69.8 vs. 61.2%; Pactivated charcoal in non-drug poisoning was also more common in males than in females (7.9 vs. 3.2%; P<0.05). There were no differences between genders as regards clinical presentation of the poisonings, delays in care, hours of emergency department stay, treatment or outcome. Benzodiazepine poisoning was more prevalent in females than in males. Non-drug poisonings and alcohol combined with drug ingestion were more common in males. The clinical outcomes of the poisonings, delays in care, therapeutic requirements and admissions were similar between genders. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  11. Return to competition in a chronic low back pain runner: beyond a therapeutic exercise approach, a case report

    Directory of Open Access Journals (Sweden)

    Sergio Veneziani

    2014-05-01

    Full Text Available 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.

  12. Return to competition in a chronic low back pain runner: beyond a therapeutic exercise approach, a case report

    Directory of Open Access Journals (Sweden)

    Sergio Veneziani

    2014-09-01

    Full Text Available 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.

  13. Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation.

    Science.gov (United States)

    Stoddard, Marcus F; Singh, Pradeep; Dawn, Buddhadeb; Longaker, Rita A

    2003-04-01

    Atrial fibrillation (AF) is widely accepted as a direct cause of cardioembolic stroke from left atrial (LA) thrombus formation. However, the relationship between LA thrombus and transient ischemic attack (TIA) in patients with AF is less well established. Two hundred sixty-one adult patients (mean age 66 +/- 11 years, 220 men and 41 women) with AF undergoing transesophageal echocardiography (TEE) were prospectively followed up for TIA (mean duration 30.3 +/- 20.6 months). LA thrombus was present in 18% (n = 46) and LA spontaneous echocardiographic contrast in 50% (n = 131) of the group. Nineteen of 261 patients had TIA during follow-up. Multivariate logistic regression showed congestive heart failure (CHF) as the only predictor of TIA when a model of clinical variables was constructed (odds ratio [OR] 2.7, P =.04). Age, sex, hypertension, and use of warfarin or aspirin were not predictors. When TEE variables were added to the model, LA thrombus became the only predictor of TIA (OR 7.7, P =.0001). Survival free of TIA (Kaplan-Meier) was significantly less (P =.0001) in patients with LA thrombus compared with those without, and the annual TIA event rate was 9.2% per year versus 1.9% per year (P likely thromboembolic mechanism for TIA from LA thrombus in patients with AF.

  14. Slow flow and mural thrombus in aortic diseases: Spin-echo MR findings and their differentiation

    International Nuclear Information System (INIS)

    Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung

    1993-01-01

    In order to evaluate the ability of spin-echo MR imaging to differentiate slow flow from mural thrombus in aortic diseases, we reviewed the spin-echo MR images of 13 patients with intraaortic thrombus documented by CT (N=11) or aortography (N=2). Six patients had aortic aneurysms and seven had aortic dissections. Intraaortic mural thrombi were accompanied by flow-related intraluminal signal of various pattern and extents in all 13 patients. On 10 gated MR studies, slow flow regions showed ever-echo rephasing phenomenon (N=8), interslice variation of signal intensities of the intraluminal signal (N=7) and flow-related ghost artifact (N=2). However, these MR flow phenomena were obscured on two of three non-gated studies. Seven of 13 intraaortic thrombi remained hyperintense on T2-weighted second-echo images. In these circumstance, a hypointense boundary layer between slow flow and mural thrombus, which was caused by either ' boundary layer dephasing phenomenon' of slow flow or 'paramagnetic T2 shortening' of fresh clot at the edge of mural thrombus, was very useful in discriminating the area of slow flow from that of mural thrombus. Proper interpretation of spin-echo MR images may obviate the need for phase display imaging or gradient-echo imaging in differentiating slow flow and mural thrombus

  15. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    Science.gov (United States)

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-10-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  16. Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Porto, Italo, E-mail: italo.porto@gmail.com [Interventional Cardiology Unit, San Donato Hospital, Arezzo (Italy); Mattesini, Alessio; Valente, Serafina [Interventional Cardiology Unit, Careggi Hospital, Florence (Italy); Prati, Francesco [Interventional Cardiology San Giovanni Hospital, Rome (Italy); CLI foundation (Italy); Crea, Filippo [Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome (Italy); Bolognese, Leonardo [Interventional Cardiology Unit, San Donato Hospital, Arezzo (Italy)

    2015-04-15

    Coronary angiography is the “golden standard” imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis. - Highlights: • Thrombotic burden in acute coronary syndromes Is not adequately evaluated by standard coronary angiography, whereas Optical Coherence Tomography is exquisitely sensitive to the hemoglobin contained in red blood cells and can be used to precisely quantify thrombus. • Both research and clinical applications have been developed using the OCT-based evaluation of thrombus. In particular, whereas precise quantification scores are useful for comparing antithrombotic therapies in randomized trials, both pharmacological and mechanical, the most important practical applications for OCT-based assessment of thrombus are the individuation of culprit lesions in the context of diffuse atheromata in acute coronary syndromes, and the so-called “delayed stenting” strategies. • Improvements in 3D rendering techniques are on the verge of revolutionizing OCT-based thrombus assessment, allowing extremely precise quantification of the thrombotic burden.

  17. Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives

    International Nuclear Information System (INIS)

    Porto, Italo; Mattesini, Alessio; Valente, Serafina; Prati, Francesco; Crea, Filippo; Bolognese, Leonardo

    2015-01-01

    Coronary angiography is the “golden standard” imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis. - Highlights: • Thrombotic burden in acute coronary syndromes Is not adequately evaluated by standard coronary angiography, whereas Optical Coherence Tomography is exquisitely sensitive to the hemoglobin contained in red blood cells and can be used to precisely quantify thrombus. • Both research and clinical applications have been developed using the OCT-based evaluation of thrombus. In particular, whereas precise quantification scores are useful for comparing antithrombotic therapies in randomized trials, both pharmacological and mechanical, the most important practical applications for OCT-based assessment of thrombus are the individuation of culprit lesions in the context of diffuse atheromata in acute coronary syndromes, and the so-called “delayed stenting” strategies. • Improvements in 3D rendering techniques are on the verge of revolutionizing OCT-based thrombus assessment, allowing extremely precise quantification of the thrombotic burden

  18. 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.

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

    International Nuclear Information System (INIS)

    Muñoz, Miguel; Coveñas, Rafael

    2015-01-01

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

  20. 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.

  1. 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

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

    Science.gov (United States)

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

    2014-08-01

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

  3. New therapeutic approach in the management of intestinal disease: probiotics in intestinal disease in paediatric age.

    Science.gov (United States)

    Cucchiara, S; Falconieri, P; Di Nardo, G; Parcelii, M A; Dito, L; Grandinetti, A

    2002-09-01

    Current evidence supports the view that oral administration of probiotics may be of therapeutic usefulness in several clinical disorders by reestablishing normal flora in the gastrointestinal tract. These entities include inflammatory and infectious diseases of the gut as well as extraintestinal disorders (such as atopic eczema) in which a defective intestinal permeability plays a role. The probiotic effects are attributed to restoration to normal of increased intestinal permeability, unbalanced gut microecology, improved immunological gut barrier function, downregulation of the intestinal inflammatory responses with reduced generation of proinflammatory cytokines. Entities for which the impact of probiotic administration can be considered as proven are Rotavirus diarrhoea, Clostridium difficile diarrhoea, post-antibiotic diarrhoea, allergic diseases. On the other hand, entities for which administration of probiotics is considered under investigation are inflammatory bowel disease, necrotizing enterocolitis, cystic fibrosis, small bowel bacterial contamination, functional gastrointestinal disorders. The value of probiotics as therapy for a variety of gastrointestinal disorders in childhood still needs to be investigated in detail, through well controlled and rigorous studies, including a placebo group and strict criteria of randomisation. Much work needs to be done in this area by clearly defining indications, delivery system, costs, safety long-term effects.

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

    Science.gov (United States)

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

    2016-11-01

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

  5. 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.

  6. Combined dynamic light scattering and Raman spectroscopy approach for characterizing the aggregation of therapeutic proteins.

    Science.gov (United States)

    Lewis, E Neil; Qi, Wei; Kidder, Linda H; Amin, Samiul; Kenyon, Stacy M; Blake, Steven

    2014-12-12

    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.

  7. Disease course and therapeutic approach in dermatomyositis: A four-center retrospective study of 100 patients.

    Science.gov (United States)

    Johnson, Nicholas E; Arnold, W David; Hebert, Donald; Gwathmey, Kelly; Dimachkie, Mazen M; Barohn, Richard J; McVey, April L; Pasnoor, Mamatha; Amato, Anthony A; McDermott, Michael P; Kissel, John; Heatwole, Chad R

    2015-08-01

    Dermatomyositis is a life-altering inflammatory disorder of skin and muscle. Details regarding the natural course of this disorder, the effects of specific therapies on its progression, and the optimal therapeutic dosage and duration of prednisone are limited. We performed a retrospective medical record review of dermatomyositis patients at four medical centers. All patients were over the age of 21 and had a clinical diagnosis of dermatomyositis with pathological confirmation. We reviewed average muscle strength, corticosteroid use, creatine kinase levels, and supplemental immunosuppressant use during the 36-month period following each patient's initial assessment. One hundred patients participated with an average age of 50.1 years. Average muscle strength improved and prednisone requirements lessened six months after initial assessment. There was no difference in the mean change in muscle strength or cumulative corticosteroid use over 36 months among those initially treated with methotrexate, mycophenolate mofetil, pulse IVIG, or azathioprine. There was a 5% mortality rate in dermatomyositis patients due to infections. Treated dermatomyositis patients demonstrate the most significant improvement in strength during the first six-to-twelve months following their initial clinical assessment. Additional prospective studies are needed to determine the relative benefit of select immunosuppressant agents in preserving strength and reducing corticosteroid use in dermatomyositis. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

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

    2017-10-24

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

  14. Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

    Science.gov (United States)

    Fuentes, Eduardo; Caballero, Julio; Alarcón, Marcelo; Rojas, Armando; Palomo, Iván

    2014-01-01

    Background Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway. PMID:24598787

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

    Science.gov (United States)

    Barnes, Peter J

    2015-09-01

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

  16. 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

  17. 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.

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

    Science.gov (United States)

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

    2014-07-01

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

  19. 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

    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...... 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...... (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...

  20. 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...

  1. 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.

  2. Self-emulsifying therapeutic system: a potential approach for delivery of lipophilic drugs

    Directory of Open Access Journals (Sweden)

    Jyoti Wadhwa

    2011-09-01

    Full Text Available Self-emulsifying therapeutic system (SETs provide an effective and intelligent solution to the various issues related to the formulation of hydrophobic drugs with limited solubility in gastrointestinal fluid. Although the potential utility of SETs is well known, only in recent years has a mechanistic understanding of the impact of these systems on drug disposition emerged. These in situ emulsion-forming systems have a high stability when incorporated in various dosage forms. SETs are being looked upon as systems which can overcome the problems associated with delivery of poorly water soluble drugs. An in-depth knowledge about lipids and surfactants that can contribute to these systems, criterion for their selection and the proportion in which they can be used, represent some crucial factors determining the in vivo performance of these systems. This article presents a comprehensive account of various types of self-emulsifying formulations with emphasis on their composition and examples of currently marketed preparations.O sistema terapêutico auto-emulsionante (SETs fornece solução eficaz e inteligente para os vários problemas relativos à formulação de fármacos hidrofóbicos com solubilidade limitada no fluido gastrintestinal. Embora a utilidade potencial dos SETs seja bem conhecida, só recentemente se compreendeu, mecanisticamente,o impacto desses sistemas na disposição de fármacos. Estes sistemas de formação de emulsão in situ têm alta estabilidade, quando incorporados em várias formas de dosagem. Os SETs têm sido considerados como sistemas que podem resolver problemas associados à liberação de fármacos pouco solúveis em água. O conhecimento profundo dos lipídios e tensoativos que podem ser utilizados para estes sistemas e o critério para a sua seleção e proporção na qual eles são utilizados são alguns dos fatores cruciais que determinam o desempenho do sistema in vivo. Este artigo apresenta o relato abrangente de

  3. Integrated therapeutic approaches in head and neck cancer: the importance of multidisciplinary team management.

    Science.gov (United States)

    Perri, Francesco; Muto, Paolo; Aversa, Corrado; Daponte, Antonio; Della Vittoria, Giuseppina; Pepe, Stefano; Caponigro, Francesco

    2013-07-01

    Multidisciplinary team (MDT) is of paramount importance in the approach to patients with head and neck cancer. Its aim is to provide the best diagnostic work-up, tumor staging, and treatment. Furthermore, the prognosis of patients who are managed by MDT is usually better. MDT has a great value in all presentation settings. The role of the pathologist in the team is of utmost importance, in particular with regards to information provided on Human Papilloma Virus (HPV) status, which has a well acknowledged independent prognostic value mainly in oropharyngeal carcinoma. In early stage disease, namely in T1-2 N0 M0 patients, the meetings within the MDT mainly involve surgeons and radiation therapists. Surgery represents the mainstay of treatment, while radiation therapy is a suitable alternative, in particular in patients with advanced age, poor performance status and comorbidities. In locally advanced disease, surgeons, medical oncologists and radiotherapists are the key people, since different approaches have been carried out. In operable patients, adjuvant chemoradiation is indicated when resection margins are involved or close, or in presence of extracapsular nodal spread. Concurrent chemoradiotherapy, preceded or not by induction chemotherapy, is the favourite approach in this setting when surgery is strictly not indicated. In recurrent/metastatic disease chemotherapy and best supportive care are the main options, although local treatments, such as reirradiation and salvage surgery, are also worth considering. The standard chemotherapy treatment has finally evolved after about 30 years, and strong efforts are being pursued to further improve the outcome, mainly with the addition of new drugs.

  4. 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.

  5. PRINZMETAL ANGINA PECTORIS IN CLINICAL PRACTICE: POSSIBILITY OF CHRONO-THERAPEUTIC APPROACH AND LIMITATIONS OF COMORBIDITY

    Directory of Open Access Journals (Sweden)

    M. V. Baeva

    2013-12-01

    Full Text Available Prinzmetal Angina (synonyms: vasospastic angina, variant angina in accordance with the definition of, it is caused by coronary artery spasm which occurs during sleep at night, between midnight and early morning and manifested with ST segment elevation on the ECG. Frequent “attachment” to the attacks of a certain period of the sleep period, gives you the opportunity to use chronomedical approaching the treatment of patients suffering from it, as demonstrated by our observation. On the other hand, for adulthood comorbidity is characteristic, and Prinzmetal is no exception, which we wanted to show, studying the clinical case.

  6. 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

  7. 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.

  8. Safety of primary percutaneous coronary intervention with and without (selective) thrombus aspiration

    International Nuclear Information System (INIS)

    Farman, M. T.; Saghir, T.; Rizvi, N. H.; Khan, N.; Zaman, K. S.; Sial, J. A.; Malik, A.

    2014-01-01

    Objective: To determine the safety and efficacy of selective thrombus aspiration during Primary Percutaneous Coronary Intervention (PCI). Methods: This observational prospective study was conducted in the catheterization laboratory of a tertiary care cardiovascular centre. A total of 150 consecutive patients who underwent primary PCI were enrolled. Aspiration was done only when thrombus burden was considered significant. After completion of procedure angiographic and electrocardiographic signs were recorded and clinical follow up was documented up to 1 year. Results: No significant difference among the groups was found in age, height, weight and other risk factors like Hypertension, Diabetes Mellitus and Smoking. In general, left anterior descending artery was culprit in 65 % of patients and more than 90 % of culprit vessels had visible thrombus. Multivessel disease was present in 38 % of patients and 22.7% had past history of myocardial infarction. Out of 150 patients 117 (78%) underwent thrombus aspiration. No significant difference was found in ST resolution within 60 minutes (72.6 vs 81.8 %; P<0.285) and myocardial blush grade II and III (41.9 vs 27.3 %; P<0.128). No difference in event free survival was observed among the two groups (80.3 vs 84.8 %; P<0.708) at one year. Conclusion: Selective thrombus aspiration in definite thrombus laden arteries and no aspiration in low or negligible thrombus burden vessels may be a safe and effective strategy in patients undergoing primary PCI. Overall poor risk profile of our patients as compared to western population necessitates further evaluation of this matter in randomized studies. (author)

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

    DEFF Research Database (Denmark)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah

    2016-01-01

    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......, 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......-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...

  10. Burkholderia cenocepacia Infections in Cystic Fibrosis Patients: Drug Resistance and Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Viola C. Scoffone

    2017-08-01

    Full Text Available Burkholderia cenocepacia is an opportunistic pathogen particularly dangerous for cystic fibrosis (CF patients. It can cause a severe decline in CF lung function possibly developing into a life-threatening systemic infection known as cepacia syndrome. Antibiotic resistance and presence of numerous virulence determinants in the genome make B. cenocepacia extremely difficult to treat. Better understanding of its resistance profiles and mechanisms is crucial to improve management of these infections. Here, we present the clinical distribution of B. cenocepacia described in the last 6 years and methods for identification and classification of epidemic strains. We also detail new antibiotics, clinical trials, and alternative approaches reported in the literature in the last 5 years to tackle B. cenocepacia resistance issue. All together these findings point out the urgent need of new and alternative therapies to improve CF patients’ life expectancy.

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

    International Nuclear Information System (INIS)

    Dubois, J.; Garel, L.

    1999-01-01

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

  12. A clinical report of Type III dens invaginatus: relevant aspects of a combined therapeutic approach.

    Science.gov (United States)

    Silva E Souza, Patricia de Almeida Rodrigues; de Almeida, Bruno Vila Nova; Tartari, Talita; Alves, Ana Claudia Braga Amoras; Tuji, Farbicio Mesquita; Silva E Souza, Mario Honorato

    2013-01-01

    Dens invaginatus is a developmental abnormality that alters dental morphology; as a result, treating this condition is a challenge for endodontic practices. This article describes how a combination of nonsurgical and surgical therapies was utilized to treat a maxillary central incisor with Type III dens invaginatus and vital pulp. The treatment plan included using computed tomography (CT) for a detailed analysis of the dental anatomy and periapical area, endodontic and surgical procedures, and a 4-year follow-up period that included periodic clinical and radiographic examinations. The follow-up examinations revealed a regression of the apical lesion and no other signs or symptoms. Based on the present case report, the authors concluded that this combination of surgical and nonsurgical approaches was effective and that CT is a valuable auxiliary tool for the study of dental anatomy.

  13. 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.

  14. 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

  15. 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.

  16. Is Transcatheter Tricuspid Valve-In-Valve Implantation Feasible in the Presence of Right Atrial Thrombus?

    Science.gov (United States)

    Henzel, Jan; Dzielińska, Zofia; Konka, Marek; Dąbrowski, Maciej; Protasiewicz, Marcin; Witkowski, Adam; Demkow, Marcin

    2017-03-01

    The case is reported of a successful transcatheter implantation of an Edwards SAPIEN 3 valve (29 mm) into a failing tricuspid bioprosthesis (Sorin Pericarbon, 31 mm). The procedure was performed in a 69-year-old woman with post-rheumatic mitral and tricuspid valve disease. Multiple previous cardiac surgeries precluded the use of another surgical approach. A large, organized, two-piece thrombus in the enlarged right atrium was not considered an absolute contraindication to the procedure. The SAPIEN 3 valve was implanted under general anesthesia, via a femoral venous access, under three-dimensional transesophageal echocardiography guidance. Postoperatively, the systolic right ventricular pressure was increased from 35 to 52 mmHg, but good function of the implanted valve was confirmed with transthoracic echocardiography. The clinical outcome was favorable and the patient was discharged home 72 h after the intervention. Video 1: Transthoracic echocardiography. Tricuspid color Doppler flow after the procedure. Video 2: Fluoroscopy. Fully expanded Edwards SAPIEN 3 valve in the tricuspid position. Video 3: Fluoroscopy. Expansion of the Edwards SAPIEN 3 valve on the balloon. Video 4: Fluoroscopy. Introduction of the Edwards SAPIEN 3 valve into the right atrium. Video 5: Transthoracic echocardiography. Tricuspid color Doppler flow before the procedure.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  18. 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.

  19. PATHOPHYSIOLOGY STROKE NON-HEMORRHAGIC ET CAUSA THROMBUS

    Directory of Open Access Journals (Sweden)

    Aji Kristianto Wijaya

    2013-10-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Stroke is one of the most common cause of death worldwide and the third leading cause of death in the United States. Stroke composed 90,000 deaths of women and 60,000 men each year. In Indonesia, 8 of 1000 people suffered a stroke. Stroke is divided into two, non-hemorrhagic stroke and hemorrhagic stroke. Most of them (80% is non-hemorrhagic stroke. Non-hemorrhagic stroke can be caused by thrombi or emboli. Understanding the pathophysiology of non-hemorrhagic stroke caused by a thrombus is very important in regard with providing appropriate patient management. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  20. Survival in patients with malignancy and venous thromboembolism by tumour subtype and thrombus location.

    Science.gov (United States)

    Prestidge, T; Lee, S; Harper, P; Young, L; Ockelford, P

    2012-01-01

    Although the association between malignancy and venous thromboembolism (VTE) is firmly established, less is known about the survival following VTE among different malignant subtypes. We sought to estimate survival from first VTE in consecutive patients with known malignancy receiving extended low molecular weight heparin therapy. Five hundred and fifty-nine consecutive patients presenting to the Thrombosis Unit Registry at Auckland City Hospital between January 1997 and October 2006 were observed. Events were confirmed by standard imaging procedures. The diagnosis date and site of VTE as well as the type of malignancy were recorded. Mean follow up was 21.4 months. Overall median survival from VTE was 13.5 months. Six-month, one-, two- and five-year survivals were 64%, 53%, 43% and 33% respectively. Survival was longest for haematological malignancy at 44.4 months, followed by prostate, bowel, breast (metastatic breast), lung and pancreatic malignancy at 29.4, 27.4, 15.5 (6.2), 2.4 and 1.9 months respectively. Median survival varied with thrombotic location from 31.1 months for upper limb/jugular deep vein thrombosis reducing to only 10.1 months for iliocaval/abdominal deep vein thrombosis, but this did not reach statistical significance. Survival from cancer diagnosis was also determined. The 1-year 53% survival in cancer patients with VTE treated using extended low molecular weight heparin is longer than that reported from large registry and population studies in which specific patient information and therapeutic regimens are unknown. Survival is critically determined by tumour type and correlates with tumour stage in women with breast cancer. There is also a trend towards differing survival by thrombus location. © 2010 The Authors. Internal Medicine Journal © 2010 Royal Australasian College of Physicians.

  1. Effect of thrombus composition and viscosity on sonoreperfusion efficacy in a model of microvascular obstruction

    Science.gov (United States)

    Black, John J.; Yu, Francois T. H.; Schnatz, Rick G.; Flordeliza, Xucai Chen; Villanueva, S.; Pacella, John J.

    2016-01-01

    Distal embolization of microthrombi during stenting for myocardial infarction (MI) causes microvascular obstruction (MVO). We have previously shown that sonoreperfusion (SRP), a microbubble (MB)-mediated ultrasonic (US) therapy, resolves MVO from venous microthrombi in vitro in saline. However, blood is more viscous than saline and arterial thrombi that embolize during stenting are mechanically distinct from venous clot. Therefore, we tested the hypothesis that MVO created with arterial microthrombi are more resistant to SRP therapy compared with venous microthrombi and higher viscosity further increases the US requirement for effective SRP in an in vitro model of MVO. Lipid MB suspended in plasma with adjusted viscosity (1.1 or 4.0 cP) were passed through tubing bearing a mesh with 40 μm pores to simulate a microvascular cross-section; upstream pressure reflected thrombus burden. To simulate MVO, the mesh was occluded with either arterial or venous microthrombi to increase upstream pressure to 40±5 mmHg. Therapeutic long-tone-burst US was delivered to the occluded area for 20 min. MB activity was recorded with a passive cavitation detector (PCD). MVO caused by arterial microthrombi at either blood or plasma viscosity resulted in less effective SRP therapy, compared to venous thrombi. Higher viscosity further reduced the effectiveness of SRP therapy. PCD showed a decrease in inertial cavitation when viscosity was increased while stable cavitation was affected in a more complex manner. Overall, these data suggest that arterial thrombi may require higher acoustic pressure US than venous thrombi to achieve similar SRP efficacy, increased viscosity decreases SRP efficacy, and both inertial and stable cavitation are implicated in observed SRP efficacy. PMID:27207018

  2. Complicated pleural effusion in children – Therapeutical approach

    Directory of Open Access Journals (Sweden)

    Sara Martins

    2007-01-01

    Full Text Available 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 (±37,0 months. Bacteria were identified in 17/25 (68% [S. aureus in 6/17 (35%, St. pneumoniae in 5/17 (29%], 16/17 (94%in the pleural fluid. Twenty-five children were treated with antibiotics and thoracocentesis (100%. Chest tube drainage was required in 22/25 (88% with mean (±DP duration of 14,2 (±7,8 days. Fibrinolitics were employed in 1 only case and surgical decortication in 11/25 (44%. One patient (4% was submitted to primary VTC. Median length of stay was 30,4 (±15,1 days and no deaths were recorded. Center skills in CPE management are critical on the choice of the technique and the timing of approach. This seems to influence immediate prognosis. Resumo: 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 poss

  3. 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.

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2015-10-29

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

  7. New Approaches and Therapeutic Options for Mycobacterium tuberculosis in a Dormant State.

    Science.gov (United States)

    Caño-Muñiz, Santiago; Anthony, Richard; Niemann, Stefan; Alffenaar, Jan-Willem C

    2018-01-01

    We are far away from the days when tuberculosis (TB) accounted for 1 in 4 deaths during the 19th century. However, Mycobacterium tuberculosis complex (MTBC) strains are still the leading cause of morbidity and mortality by a single infectious disease, with 9.6 million cases and 1.5 million deaths reported. One-third of the world's population is estimated by the WHO to be infected with latent TB. During the last decade, several studies have aimed to define the characteristics of dormant bacteria in these latent infections. General features of the shift to a dormant state encompass several phenotypic changes that reduce metabolic activity. This low metabolic state is thought to increase the resistance of MTBC strains to host/environmental stresses, including antibiotic action. Once the stress ceases (e.g., interruption of treatment), dormant cells can reactivate and cause symptomatic disease again. Therefore, a proper understanding of dormancy could guide the rational development of new treatment regimens that target dormant cells, reducing later relapse. Here, we briefly summarize the latest data on the genetics involved in the regulation of dormancy and discuss new approaches to TB treatment. Copyright © 2017 American Society for Microbiology.

  8. 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.

  9. [Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

    Science.gov (United States)

    Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

    2015-11-01

    Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

  10. Review of Mechanical Testing and Modelling of Thrombus Material for Vascular Implant and Device Design.

    Science.gov (United States)

    Johnson, S; Duffy, S; Gunning, G; Gilvarry, M; McGarry, J P; McHugh, P E

    2017-11-01

    A thrombus or blood clot is a solid mass, made up of a network of fibrin, platelets and other blood components. Blood clots can form through various pathways, for example as a result of exposed tissue factor from vascular injury, as a result of low flow/stasis, or in very high shear flow conditions. Embolization of cardiac or vascular originating blood clots, causing an occlusion of the neurovasculature, is the major cause of stroke and accounts for 85% of all stroke. With mechanical thrombectomy emerging as the new standard of care in the treatment of acute ischemic stroke (AIS), the need to generate a better understanding of the biomechanical properties and material behaviour of thrombus material has never been greater, as it could have many potential benefits for the analysis and performance of these treatment devices. Defining the material properties of a thrombus has obvious implications for the development of these treatment devices. However, to-date this definition has not been adequately established. While some experimentation has been performed, model development has been extremely limited. This paper reviews the previous literature on mechanical testing of thrombus material. It also explores the use of various constitutive and computational models to model thrombus formation and material behaviour.

  11. Therapeutic radionuclides

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Hong, Young Don; Lee, So Young

    2006-01-01

    Since the development of sophisticated molecular carriers such as octereotides for peptide receptor targeting and monoclonal antibodies against various associated with specific tumor types, radionuclide therapy (RNT) employing open sources of therapeutic agents is promising modality for treatment of tumors. Furthermore, the emerging of new therapeutic regimes and new approaches for tumor treatment using radionuclide are anticipated in near future. In targeted radiotherapy using peptides and other receptor based carrier molecules, the use of radionuclide with high specific activity in formulating the radiopharmaceutical is essential in order to deliver sufficient number of radionuclides to the target site without saturating the target. In order to develop effective radiopharmaceuticals for therapeutic applications, it is crucial to carefully consider the choice of appropriate radionuclides as well as the carrier moiety with suitable pharmacokinetic properties that could result in good in vivo localization and desired excretion. Up to date, only a limited number of radionuclides have been applied in radiopharmaceutical development due to the constraints in compliance with their physical half-life, decay characteristics, cost and availability in therapeutic applications. In this review article, we intend to provide with the improved understanding of the factors of importance of appropriate radionuclide for therapy with respect to their physical properties and therapeutic applications

  12. Hemodynamic change by portal tumor thrombus in hepatocellular carcinoma; evaluation by combined spiral CT hepatic arteriography and CT arterial portography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mee Ran; Kim, Yun Hwan; Kim, Kyung A; Seol, Hae Young; Chung, Kyoo Byung; Suh, Won Hyuk [Korea Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-01-01

    To evaluate the hemodynamioc change by portal tumor thrombus in hepatocellular carcinoma(HCC). We reviewed 35 cases of combined spiral CTHA and CTAP in 25 HCC patients with portal tumor thrombus from April 1993 to October 1994, regarding to portal tumor thrombus, the involved area of arterioportal(AP) shunt and the development of cavernous transformation of portal vein, in comparison with hepatic and superior mesenteric arteriography. Spiral CTHA showed hyperattenuating tumor, portal tumor thrombus and hyperattenuating peritumoral parenchymal area. Spiral CTAP showed perfusion defect area including tumor, portal tumor thrombus and peritumoral area distal to portal vein obstruction. In 15 cases, portal tumor thrombus showed intraluminal and marginal hyperattenuating linear structures on CTHA due to transvasal AP shunt and tumor feeding arteries, which were corresponding to thread and streaks sign on hepatic arteriography. Cavernous transformation of portal vein was demonstrated in 15 cases as irregular periportal hyperattenuating collateral vessels on spiral CTAP. In 32 cases, portal vein was visualized on CTHA due to AP shunt. And according to shunt amount, we classified AP shunt into 4 grades. Grade I means only the presence of portal tumor thrombus without Ap shunt, grade II with segmental AP shunt, grade III with one lobar AP shunt, and grade IV with both lobar AP shunt or the presence of cavernous transformation of portal vein. Grade I was seen in 3, grade II in 4, grade III in 13 and grade IV in 15 cases. Variable CTHA and CTAP findings were shown in HCC patients with portal tumor thrombus according to the amount of AP shunt and the presence of cavernous transformation of portal vein. Combined CTHA and CTAP are useful to differentiate the tumor thrombus from simple thrombus and are very sensitive method for detecting AP shunt. Understanding these findings related with portal tumor thrombus is important to predict patient's prognosis and to decide

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

    Science.gov (United States)

    Duffau, Hugues; Taillandier, Luc

    2015-03-01

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

  14. 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

  15. [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.

  16. Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Xing-chen Peng

    Full Text Available Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05 were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1, significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05. In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma.

  17. Intense 18F-FDG uptake in an organizing right atrial thrombus mimicking malignancy

    Directory of Open Access Journals (Sweden)

    Krishna G. Chaudhuri, MD

    2017-09-01

    Full Text Available We present a case of an intensely hypermetabolic intracavitary cardiac mass, standardized uptake values max 44.4, that was pathologically proved to be organizing and organized thrombus, negative for tumor. Our patient had previous right atrial mass resection 2 years prior that was pathologically described as either thrombus or infarcted atrial myxoma. She had since been on lifelong controlled anticoagulation; and on routine follow-up imaging, she had recurrent slow growth of a new right atrial mass. During a later hospital admission for chest pain, the mass was evaluated on both transthoracic and transesophageal echo cardiogram, which could not differentiate thrombus vs neoplasm. Cardiac magnetic resonance imaging was equivocal for mass enhancement. The patient underwent fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT evaluation, which revealed intensely hypermetabolic activity within the mass concerning for malignancy, potentially an aggressive tumor. Subsequently, the mass was surgically excised for pathological diagnosis.

  18. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries

    Directory of Open Access Journals (Sweden)

    Papasian Christopher J

    2011-04-01

    .7 μg/mL in plasma and 3.8 vs 3.9 μg/mL in platelets. Conclusions The present results indicate that intravenously administered tocotrienols inhibited acute platelet-mediated thrombus formation, and collagen and ADP-induced platelet aggregation. α-Tocotrienols treatment induced increases in α-tocopherol levels of 4-fold and 6-fold in plasma and platelets, respectively. Interestingly, tocotrienols (TRF treatment induced a less pronounced increase in the levels of tocotrienols in plasma and platelets, suggesting that intravenously administered tocotrienols may be converted to tocopherols. Tocotrienols, given intravenously, could potentially prevent pathological platelet thrombus formation and thus provide a therapeutic benefit in conditions such as stroke and myocardial infarction.

  19. 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

  20. Severe reversible dilated cardiomyopathy associated with a large left ventricular thrombus in a young child with middle aortic syndrome

    OpenAIRE

    Ponniah, U; Overholt, E

    2014-01-01

    this article reports a case of a seven-year girl who presented with severe dilated cardiomyopathy (DCM) associated with a large thrombus in the left ventricle (LV). She had a long segment stenosis of the lower thoracic descending aorta, possibly due to non-specific aortitis and underwent successful stent angioplasty. The LV thrombus resolved after heparin without sequelae.

  1. Abnormal neural connectivity in schizophrenia and fMRI-brain computer interface as a potential therapeutic approach

    Directory of Open Access Journals (Sweden)

    Sergio eRuiz

    2013-03-01

    Full Text Available Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the abnormal neural connectivity hypothesis. In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia.The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem.

  2. 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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Benedetta M. Motta

    2017-01-01

    Full Text Available 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.

  5. 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.

  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. 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

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

    Science.gov (United States)

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

    2015-01-01

    “The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach” was held at the Renaissance Orlando at SeaWorld Hotel (August 2–4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. PMID:25900621

  9. Greenfield filter caval perforation causing an aortic mural thrombus and femoral artery occlusion.

    Science.gov (United States)

    Chintalapudi, U B; Gutierrez, O H; Azodo, M V

    1997-05-01

    A 32-year-old woman suffered a right femoral artery embolic occlusion from an abdominal aortic mural thrombus associated with caval perforation by a stainless steel Greenfield Filter. The complication required thrombolytic therapy, surgical revascularization, and long-term anticoagulation.

  10. Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death

    NARCIS (Netherlands)

    Kramer, Miranda C. A.; Rittersma, Saskia Z. H.; de Winter, Robbert J.; Ladich, Elena R.; Fowler, David R.; Liang, You-Hui; Kutys, Robert; Carter-Monroe, Naima; Kolodgie, Frank D.; van der Wal, Allard C.; Virmani, Renu

    2010-01-01

    OBJECTIVES: The aim of this study was to assess differences in thrombus healing between ruptured and eroded plaques, given the natural difference in lesion substrate and that thrombi might exist days to weeks before the presentation of sudden coronary death. BACKGROUND: Although the ability to

  11. Computational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow Conditions

    Science.gov (United States)

    2016-04-26

    generation biochemistry , and fibrin formation and function, and was able to predict essential dynamic features of the thrombus formation pro- cess observed in...Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MarylandABSTRACT A comprehensive... biochemistry , structural biology, and rheology have been extensively investigated. Such studies provide in- formation about the biochemical reactions

  12. Unusual Presentation of Testicular Cancer with Tumor Thrombus Extending to the Inferior Vena Cava

    Directory of Open Access Journals (Sweden)

    Marie Dusaud

    2015-01-01

    Full Text Available A 45-year-old man with a left testis tumor with a 25 mm para-aortic lymph node swelling, multiple bilateral pulmonary metastases, bilateral pulmonary embolism, and inferior vena cava (IVC thrombus underwent a radical orchidectomy in our institution. The thrombus extended from the left gonadal vein to the left renal vein to the IVC. The fluorine-18 fluorodeoxyglucose (f-FDG positron emission tomography (PET computerized tomography (CT demonstrated a hypermetabolic focus in the retroperitoneum and in the IVC thrombus. Before orchidectomy only lactate dehydrogenase (LDH was high but all the serum tumor markers increased postoperatively. The tumor was staged pT1N2M1aS1, which was an intermediate prognosis, based on the International Germ Cell Cancer Collaborative Group consensus (IGCCCG. After 4 courses of bleomycin, etoposide, and cisplatin (BEP chemotherapy the patient’s tumor markers normalized and the thrombus disappeared. There was only one residual retroperitoneal lymph node M1. Retroperitoneal lymph node dissection was performed. The pathological examination revealed only necrotic tissues. The patient has been disease-free since surgery.

  13. CORONARY EMBOLISM WITH FRAGMENTED THROMBUS FROM THE LEFT VENTRICLE IN PATIENT WITH POSTINFARCTION ANEURYSM

    Directory of Open Access Journals (Sweden)

    Yu. F. Salakhova

    2011-01-01

    Full Text Available The thrombus formation in the left ventricle (LV cavity is a frequent complication of myocardial infarction (MI as well as a risk factor for peripheral arterial embolism. Probability of intraventricular thrombus depends on MI location and its therapy. A case of coronary embolism in a patient with anterior MI and thrombus in the LV aneurysm is considered in details. Successful percutaneous coronary intervention (PCI in the first 90 minutes after admission was performed. Decision to appoint a three-component antithrombotic therapy (acetylsalicylic acid, clopidogrel, warfarin was made on the 4th day of disease onset taking into account the combination of MI, stent placement in the anterior interventricular artery and the presence of left ventricular aneurysm with parietal thrombus. Recurrence of MI developed on the 9th day of disease onset. Aspiration thromboembolectomy was performed taking into account thrombosis of two coronary arteries. Warfarin therapy was discontinued in connection with subsequent clot lysis and development of not intensive nosebleed. Subsequent MI course was uneventful. In conclusion, even in spite of the timely achievement of PCI and early reperfusion, MI course can be complicated by thrombosis of the left ventricle and subsequent development of thromboembolic complications.

  14. Saphenous vein graft thrombus findings by scanning electron microscopy in a patient with acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Marcela Dias; Aguillera, André Haraguti [Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Brilhante, José Joaquim; Caixeta, Adriano [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2013-07-01

    An eighty-year-old male patient with a history of prior (19 years) coronary artery bypass graft surgery was admitted to the hospital with non ST-segment elevation myocardial infarction (NSTEMI). During the hospital stay he was taking acetylsalicylic acid 100mg per day, a loading dose of 600mg clopidogrel, and low molecular weight heparin 1mg/kg twice a day. Twenty-four hours later the patient underwent coronary angiography, which showed a 90% obstruction in the mid portion of the saphenous vein graft to obtuse marginal with signs of degeneration and local thrombus (Figure 1). Thrombus aspiration was performed with a 6-Fr Export{sup ™} catheter (Medtronic, Santa Rosa, CA, USA), which removed small reddish colored fragments. They were fixed in 2,5% glutaraldehyde in a 0.1M sodium cacodilate buffer. The material was processed following the GOTO protocol in which the fragments were washed with osmium tetroxide and titanic acid, after which they were dried in a critical-point device and a golden bath. Scanning electron microscopy and high definition photos (3,000 to 27,221x magnification) were obtained by the FEI Quanta{sup ™} FEG SEM device (FEI Company, Hillsboro, OR, USA). The images showed that the thrombus was rich in activated platelets, with few erythrocytes or inflammatory cells. Many cholesterol crystals were observed (Figures 2 to). The fibrin networks were sparse and thin, which is compatible with a short ischemic time and recent thrombus formation.

  15. Computational Fluid Dynamics and Aortic Thrombus Formation Following Thoracic Endovascular Aortic Repair.

    Science.gov (United States)

    Nauta, Foeke J H; Lau, Kevin D; Arthurs, Christopher J; Eagle, Kim A; Williams, David M; Trimarchi, Santi; Patel, Himanshu J; Figueroa, Carlos A

    2017-06-01

    We present the possible utility of computational fluid dynamics in the assessment of thrombus formation and virtual surgical planning illustrated in a patient with aortic thrombus in a kinked ascending aortic graft following thoracic endovascular aortic repair. A patient-specific three-dimensional model was built from computed tomography. Additionally, we modeled 3 virtual aortic interventions to assess their effect on thrombosis potential: (1) open surgical repair, (2) conformable endografting, and (3) single-branched endografting. Flow waveforms were extracted from echocardiography and used for the simulations. We used the computational index termed platelet activation potential (PLAP) representing accumulated shear rates of fluid particles within a fluid domain to assess thrombosis potential. The baseline model revealed high PLAP in the entire arch (119.8 ± 42.5), with significantly larger PLAP at the thrombus location (125.4 ± 41.2, p fluid dynamics may assist in the prediction of aortic thrombus formation in hemodynamically complex cases and help guide repair strategies. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham

    2011-01-01

    Platelet P2Y₁₂ receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y₁₂ antagonists are clinically used for restricted periods, but possible differences in platelet function recovery ...

  17. Thrombus Development on a Transseptal Sheath in the Right Atrium Before Electrical Pulmonary Vein Isolation

    Directory of Open Access Journals (Sweden)

    Nieves Romero-Rodriguez

    2008-02-01

    Full Text Available We describe the case of a patient who developed a thrombus on the transseptal sheath in the right atrium before transseptal puncture for circumferential pulmonary vein isolation for paroxysmal atrial fibrillation treatment. The use of intracardiac echocardiography allowed to its identification and probably prevented the patient from suffering a serious thromboembolic complication.

  18. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke

    NARCIS (Netherlands)

    Santos, Emilie M. M.; Marquering, Henk A.; den Blanken, Mark D.; Berkhemer, Olvert A.; Boers, Anna M. M.; Yoo, Albert J.; Beenen, Ludo F.; Treurniet, Kilian M.; Wismans, Carrie; van Noort, Kim; Lingsma, Hester F.; Dippel, Diederik W. J.; van der Lugt, Aad; van Zwam, Wim H.; Roos, Yvo B. W. E. M.; van Oostenbrugge, Robert J.; Niessen, Wiro J.; Majoie, Charles B.; Fransen, Puck S. S.; Beumer, Debbie; van den Berg, Lucie A.; Schonewille, Wouter J.; Vos, Jan Albert; Nederkoorn, Paul J.; Wermer, Marieke J. H.; van Walderveen, Marianne A. A.; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A.; Lycklama à Nijeholt, Geert J.; Boiten, Jelis; Brouwer, Patrick A.; Emmer, Bart J.; de Bruijn, Sebastiaan F.; van Dijk, Lukas C.; Kappelle, L. Jaap; Lo, Rob H.; van Dijk, Ewoud J.; de Vries, Joost; de Kort, Paul L. M.; van den Berg, Jan S. P.; van Hasselt, Boudewijn A. A. M.; Aerden, Leo A. M.; Dallinga, René J.; Visser, Marieke C.; Bot, Joseph C. J.; Vroomen, Patrick C.; Eshghi, Omid; Schreuder, Tobien H. C. M. L.; Heijboer, Roel J. J.; Keizer, Koos; Tielbeek, Alexander V.; den Hertog, Heleen M.; Gerrits, Dick G.; van den Berg-Vos, Renske M.; Karas, Giorgos B.; Sprengers, Marieke E. S.; Jenniskens, Sjoerd F. M.; van den Berg, René; Koudstaal, Peter J.; Flach, H. Zwenneke; Steyerberg, Ewout W.; Brown, Martin M.; Liebig, Thomas; Stijnen, Theo; Andersson, Tommy; Mattle, Heinrich P.; Wahlgren, Nils; van der Heijden, Esther; Ghannouti, Naziha; Fleitour, Nadine; Hooijenga, Imke; Lindl-Velema, Annemieke; Puppels, Corina; Pellikaan, Wilma; Janssen, Kirsten; Aaldering, Nicole; Elfrink, Marjan; de Meris, Joke; Geerlings, Annet; van Vemde, Gina; de Ridder, Ans; Greebe, Paut; de Bont-Stikkelbroeck, José; Struijk, Willy; Simons, Tiny; Messchendorp, Gert; van der Minne, Friedus; Bongenaar, Hester; Bodde, Karin; Licher, Silvan; Boodt, Nikki; Ros, Adriaan; Venema, Esmee; Slokkers, Ilse; Ganpat, Raymie-Jayce; Mulder, Maxim; Saiedie, Nawid; Heshmatollah, Alis; Schipperen, Stefanie; Vinken, Stefan; van Boxtel, Tiemen; Koets, Jeroen; Boers, Merel; Borst, Jordi; Jansen, Ivo; Kappelhof, Manon; Lucas, Marit; Geuskens, Ralph; Barros, Renan Sales; Dobbe, Roeland; Csizmadia, Marloes

    2016-01-01

    Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We

  19. Pancreatic neuroendocrine tumor with splenic vein tumor thrombus: A case report

    Directory of Open Access Journals (Sweden)

    Rodrigo A. Rodriguez

    2014-01-01

    CONCLUSION: En bloc resection of primary tumor, involved organs and thrombus is the recommended treatment option and often results in long term survival. New multi-modality strategies are needed for detection of venous involvement in nonfunctional PNET to better assist with preoperative planning and counseling.

  20. 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

  1. Molecules of the quinoline family block tau self-aggregation: implications toward a therapeutic approach for Alzheimer's disease.

    Science.gov (United States)

    Navarrete, Leonardo P; Guzmán, Leonardo; San Martín, Aurelio; Astudillo-Saavedra, Luis; Maccioni, Ricardo B

    2012-01-01

    The neurofibrillary tangles (NFTs) generated by self-aggregation of anomalous forms of tau represent a neuropathological hallmark of Alzheimer's disease (AD). These lesions begin to form long before the clinical manifestation of AD, and its severity is correlated with cognitive impairment in patients. We focused on the search for molecules that interact with aggregated tau of the Alzheimer's type and that may block its aggregation before the formation of NFTs. We show that molecules from a family of quinolines interact specifically with oligomeric forms of tau, inhibiting their assembly into AD filaments. The quinolines 2-(4-methylphenyl)-6-methyl quinoline (THQ-4S) and 2-(4-aminophenyl)-6-methylquinoline (THQ-55) inhibited in vitro aggregation of heparin-induced polymers of purified brain tau and aggregates of human recombinant tau. They also interact with paired helical filaments (PHFs) purified from AD postmortem brains. In vitro studies indicated a significantly lower inhibitory effect of amyloid-β42 on the aggregation, suggesting that tau aggregates are specific targets for quinoline interactions. These compounds showed highly lipophilic properties as corroborated with the analysis of total polar surface areas, and evaluation of their molecular properties. Moreover, these quinolines exhibit physical chemical properties similar to drugs able to penetrate the human brain blood barrier. Docking studies based on tau modeling, as a structural approach to the analysis of the interaction of tau-binding ligands, indicated that a C-terminal tau moiety, involved in the formation of PHFs, seems to be a site for binding of quinolines. Studies suggest the potential clinical use of these quinolines and of their derivatives to inhibit tau aggregation and possible therapeutic routes for AD.

  2. Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach.

    Directory of Open Access Journals (Sweden)

    Fujun Jin

    Full Text Available Herpes simplex virus type 1 (HSV-1, a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency. During the proliferation of HSV-1, capsid assembly is essential for viral growth, and it is highly conserved in all HSV-1 strains. In this study, small interfering RNAs (siRNAs against the HSV-1 capsid protein were screened to explore the influence of silencing capsid expression on the replication of HSV-1. We designed and chemically synthesized siRNAs for the capsid gene and assessed their inhibitory effects on the expression of target mRNA and the total intracellular viral genome loads by quantitative real-time PCR, as well as on the replication of HSV-1 via plaque reduction assays and electron microscopy. Our results showed that siRNA was an effective approach to inhibit the expression of capsid protein encoding genes including UL18, UL19, UL26, UL26.5, UL35 and UL38 in vitro. Interference of capsid proteins VP23 (UL18 and VP5 (UL19 individually or jointly greatly affected the replication of clinically isolated acyclovir-resistant HSV-1 as well as HSV-1/F and HSV-2/333. Plaque numbers and intracellular virions were significantly reduced by simultaneous knockdown of UL18 and UL19. The total intracellular viral genome loads were also significantly decreased in the UL18 and UL19 knockdown groups compared with the viral control. In conclusion, interfering with UL18 and UL19 gene expression could inhibit HSV-1 replication efficiently in vitro. Our research offers new targets for an RNA interference-based therapeutic strategy against HSV-1.

  3. Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach.

    Science.gov (United States)

    Jin, Fujun; Li, Shen; Zheng, Kai; Zhuo, Cuiqin; Ma, Kaiqi; Chen, Maoyun; Wang, Qiaoli; Zhang, Peizhuo; Fan, Jianglin; Ren, Zhe; Wang, Yifei

    2014-01-01

    Herpes simplex virus type 1 (HSV-1), a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency. During the proliferation of HSV-1, capsid assembly is essential for viral growth, and it is highly conserved in all HSV-1 strains. In this study, small interfering RNAs (siRNAs) against the HSV-1 capsid protein were screened to explore the influence of silencing capsid expression on the replication of HSV-1. We designed and chemically synthesized siRNAs for the capsid gene and assessed their inhibitory effects on the expression of target mRNA and the total intracellular viral genome loads by quantitative real-time PCR, as well as on the replication of HSV-1 via plaque reduction assays and electron microscopy. Our results showed that siRNA was an effective approach to inhibit the expression of capsid protein encoding genes including UL18, UL19, UL26, UL26.5, UL35 and UL38 in vitro. Interference of capsid proteins VP23 (UL18) and VP5 (UL19) individually or jointly greatly affected the replication of clinically isolated acyclovir-resistant HSV-1 as well as HSV-1/F and HSV-2/333. Plaque numbers and intracellular virions were significantly reduced by simultaneous knockdown of UL18 and UL19. The total intracellular viral genome loads were also significantly decreased in the UL18 and UL19 knockdown groups compared with the viral control. In conclusion, interfering with UL18 and UL19 gene expression could inhibit HSV-1 replication efficiently in vitro. Our research offers new targets for an RNA interference-based therapeutic strategy against HSV-1.

  4. In vivo application of beta amyloid oligomers: a simple tool to evaluate mechanisms of action and new therapeutic approaches.

    Science.gov (United States)

    Balducci, Claudia; Forloni, Gianluigi

    2014-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cerebral accumulation of extracellular amyloid β (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau protein, two main lesions which appear sequentially during the disease progression. In the last decade numerous studies have proposed small soluble aggregates of Aβ, known as oligomers, as the species responsible for synaptic dysfunction, memory loss and neurodegeneration typical of AD. In vitro and in vivo experiments have identified Aβ oligomers as the elements that can alter synaptic function by a reversible mechanism, which gradually becomes permanent when exposure is continuous. Here we show that intracerebroventricular (ICV) injection in mice of a solution containing specifically Aβ1-42 oligomers substantially affects their memory when tested in the novel object recognition task. This acute mouse model enabled us to distinguish whether oligomers were affecting specific phases of the memory processing. A single injection of Aβ1-42 oligomers before memory consolidation abolished information processing, leading to memory impairment, whereas no such effects were observed when the injection was done once the information had been processed, indicating that the oligomers affect memory consolidation rather than retrieval. Beside Aβ1-42, Aβ1-40 oligomers also impaired memory, and both isoforms were antagonized by the anti-Aβ4G8 monoclonal antibody. This simple and reliable paradigm is useful to investigate the mechanisms through which Aβ oligomers interfere with neuronal processes and to test the efficacy of new therapeutic approaches specifically against these species. We tested several molecules by direct coincubation with Aβ oligomers, ICV injections preceding Aβ oligomers, and the systemic treatment with drugs that cross the blood brain barrier. We also examined the proposed involvement of cellular prion protein as a mediator of the oligomer-induced memory impairment.

  5. Finding the origin of pulmonary emboli with a total-body magnetic resonance direct thrombus imaging technique

    Science.gov (United States)

    van Langevelde, Kirsten; Šrámek, Alexandr; Vincken, Patrice W.J.; van Rooden, Jan-Kees; Rosendaal, Frits R.; Cannegieter, Suzanne C.

    2013-01-01

    Pulmonary embolism is considered to originate from embolization of a deep-vein thrombosis, resulting in two manifestations of one disease: venous thrombosis. However, in up to 50% of patients with pulmonary embolism no deep-vein thrombosis is found with ultrasonography. An explanation for this low proportion is currently lacking. Other imaging modalities may increase the yield of detection of deep-vein thrombosis in the calf or in the abdominal region. Alternatively, not all pulmonary emboli may originate from deep-vein thromboses in the extremities. We searched for the origin of pulmonary emboli, by performing total-body magnetic resonance imaging-scans to visualize thrombi. Ninety-nine patients with a first pulmonary embolism confirmed by computed tomography underwent a magnetic resonance direct thrombus imaging-scan, a validated technique using endogenous contrast. Additionally, acquired and genetic risk factors were assessed. No thrombus was found in 55 patients, whereas a thrombus was identified in 44 patients. The commonest thrombus location was the lower leg; 12 patients had isolated calf vein thrombosis and five had isolated superficial vein thrombosis. A peripheral thrombus was found by magnetic resonance imaging in less than half of patients with pulmonary embolism. We propose several hypotheses to explain the absence of thrombi, such as a cardiac thrombus origin or embolization of the whole deep-vein thrombus. The possibility that pulmonary embolism arises de novo in the lungs, due to local inflammation-driven coagulation, needs to be considered. PMID:22801962

  6. Optical Dynamic Analysis of Thrombus Inside a Centrifugal Blood Pump During Extracorporeal Mechanical Circulatory Support in a Porcine Model.

    Science.gov (United States)

    Fujiwara, Tatsuki; Sakota, Daisuke; Ohuchi, Katsuhiro; Endo, Shu; Tahara, Tomoki; Murashige, Tomotaka; Kosaka, Ryo; Oi, Keiji; Mizuno, Tomohiro; Maruyama, Osamu; Arai, Hirokuni

    2017-10-01

    Complications due to pump thrombus remain the weak point of mechanical circulatory support (MCS), such as the use of a left ventricular assist device (LVAD) or extracorporeal membrane oxygenation, leading to poor outcomes. Hyperspectral imaging (HSI) is an effective imaging method using a hyperspectral (HS) camera, which comprises a spectrophotometer and a charge-coupled device camera to discriminate thrombus from whole blood. Animal experiments were conducted to analyze dynamic imaging of thrombus inside a prototype of a hydrodynamically levitated centrifugal blood pump using an HSI system. Six pigs were divided into a venous circulation group (n = 3) and an arterial circulation group (n = 3). Inflow and outflow cannulae were inserted into the jugular veins in the venous circulation group. The latter simulated an LVAD application. To create thrombogenic conditions, pump flow was maintained at 1 L/min without anticoagulation. An image of the bottom surface of the pump was captured by the HS camera every 4 nm over the wavelength range of 608-752 nm. Real-time dynamic images of the inside of the pump were displayed on the monitor. Appearance of an area displaying thrombus was detected within 24 h after the start of the circulation in every experiment. This imaging system also succeeded in determining the origins of pump thrombus: from inside the pump in two cases, and from outside in four cases. Two main possible sources of pump thrombus originating outside the pump were identified on autopsy: wedge thrombus around the inflow cannula; and string-like thrombus at the junction between the pump inlet and circuit tube. The results of this study from close observation of the changing appearance of pump thrombus may contribute to improvements in the safety of extracorporeal MCS. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  7. Frequency and predictors of thrombus inside the guiding catheter during interventional procedures: an optical coherence tomography study.

    Science.gov (United States)

    Scalone, Giancarla; Brugaletta, Salvatore; Garcia-Garcia, Hector M; Martin-Yuste, Victoria; Azpeitia, Yajaziel; Otsuki, Shuji; Gomez, Omar; Freixa, Xavier; Masotti, Monica; Sabaté, Manel

    2015-02-01

    Optical coherence tomography (OCT) is able to identify thrombus. We detect the frequency of thrombus inside the guiding catheter by OCT and its relationship with clinical and procedural factors. We screened 77 patients who underwent OCT pullbacks. Only patients with visible guiding catheter were finally included (35) and divided into thrombus (21) or no-thrombus group (14). Patients within thrombus group were mostly males (100 vs. 71 %, p = 0.05), with acute coronary syndrome (76 vs. 36 %, p = 0.02) and received more frequently percutaneous coronary intervention (86 vs. 43 %, p = 0.01) as compared to other group. A second dose of heparin was more frequently administered in thrombus than in other group (86 vs. 50 %, p = 0.01). Time between first heparin administration and OCT pullback (41[28-57] vs. 20 min [10-32], p = 0.001), time elapsed from second heparin administration and OCT pullback (29 [19-48] vs. 16 min [12-22], p = 0.002) and total procedural time (47 [36-69] vs. 31 min [26-39], p = 0.005) were longer in thrombus compared to other group. At multivariate analysis, total procedural time and time between first heparin administration and OCT pullback were only predictors of intra-catheter thrombus (HR 0.6 [0.3-0.9], p = 0.03 and HR 1.9 [1.1-3.2], p = 0.02, respectively). Thrombus inside guiding catheter may be a frequent finding in long interventional procedure. Future studies are warranted to determine its clinical impact.

  8. Unnatural milieu: Thrombus after transcatheter mitral valve replacement.

    Science.gov (United States)

    Khan, Jaffar M; Lederman, Robert J

    2017-08-01

    What the article teaches Transcatheter heart valve thrombosis in the mitral position causes increased valve gradients, valve dysfunction, and symptoms, and may be associated with lack of therapeutic anticoagulation. How it will impact practice Anticoagulation with a vitamin K antagonist should be considered in all patients undergoing transcatheter mitral valve replacement. What new research/study would help answer the question posed Efficacy, optimal duration, and safety of anticoagulation therapy, balancing reduced thrombosis against increased bleeding risk, needs to be assessed in larger cohort studies and prospective trials. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Eugenia Tęgowska

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0478 TITLE: Novel Therapeutic Approaches for the Treatment of Depression and Cognitive Deficits in a Rodent Model of...Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in...designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of

  12. Placement and retrieval of a Guenther tulip filter in patients with a free floating thrombus in inferior vena cava

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Min Hyun; Kim, Young Hwan; Lee, Sang Kwon; Choi, Jin Soo; Kim, Mi Jeong; Koo, Ja Hyun; Kim, Hyoung Tae; Cho, Won Hyun [Keimyung University College of Medicine, Daegu (Korea, Republic of); Seong, Nak Kwan [Daegu Catholic School of Medicine, Daegu (Korea, Republic of)

    2005-07-15

    We wanted to assess the technical feasibility and clinical efficacy of the placement and retrieval of a Guenther Tulip filter for the prevention of fatal pulmonary embolism during the management of patients with a free floating thrombus in their inferior vena ca va (IVC). Six patients having a free floating thrombus in their IVC (three patients with an isolated free floating thrombus in the IVC that resulted from immobilization due to traumatic liver injury or cerebral infarction, two patients with coexisting deep vein thrombosis in the left lower extremity that was caused by May-Thurner syndrome, and one patient with coexisting deep vein thrombosis in the right lower extremity that was due to nephrotic syndrome and immobilization after hip joint replacement) underwent placement and retrieval of a Guenther Tulip filter. The placement of the filter was performed through the right internal jugular vein to prevent the risk of detachment of the thrombus during the procedure. Retrieval of filter was performed after the free floating thrombus of the IVC had disappeared on follow-up CT because of anticoagulation therapy, aspiration thrombectomy or catheter directed Urokinase thrombolysis. The Guenther Tulip filter was successfully placed in the IVC in all six patients and it was retrieved after the management of the free floating thrombus. The mean duration of the placement of the filter was 11 days (range:7-25 days). Two patients underwent placement of an iliac vein stent for the management of May-Thurner syndrome. Detachment of the free floating thrombus in the IVC and the subsequent thrombus entrapment in the filter were documented during aspiration thrombectomy or Urokinase thrombolysis in four patients. Recurrent thrombus didn't occur during the follow-up period (range:3-20 months) in five of the six patients. In one patient, a recurrent thrombus due to the discontinuance of anticoagulation therapy was identified at the filter detachment site of the IVC on the

  13. Placement and retrieval of a Guenther tulip filter in patients with a free floating thrombus in inferior vena cava

    International Nuclear Information System (INIS)

    Seong, Min Hyun; Kim, Young Hwan; Lee, Sang Kwon; Choi, Jin Soo; Kim, Mi Jeong; Koo, Ja Hyun; Kim, Hyoung Tae; Cho, Won Hyun; Seong, Nak Kwan

    2005-01-01

    We wanted to assess the technical feasibility and clinical efficacy of the placement and retrieval of a Guenther Tulip filter for the prevention of fatal pulmonary embolism during the management of patients with a free floating thrombus in their inferior vena ca va (IVC). Six patients having a free floating thrombus in their IVC (three patients with an isolated free floating thrombus in the IVC that resulted from immobilization due to traumatic liver injury or cerebral infarction, two patients with coexisting deep vein thrombosis in the left lower extremity that was caused by May-Thurner syndrome, and one patient with coexisting deep vein thrombosis in the right lower extremity that was due to nephrotic syndrome and immobilization after hip joint replacement) underwent placement and retrieval of a Guenther Tulip filter. The placement of the filter was performed through the right internal jugular vein to prevent the risk of detachment of the thrombus during the procedure. Retrieval of filter was performed after the free floating thrombus of the IVC had disappeared on follow-up CT because of anticoagulation therapy, aspiration thrombectomy or catheter directed Urokinase thrombolysis. The Guenther Tulip filter was successfully placed in the IVC in all six patients and it was retrieved after the management of the free floating thrombus. The mean duration of the placement of the filter was 11 days (range:7-25 days). Two patients underwent placement of an iliac vein stent for the management of May-Thurner syndrome. Detachment of the free floating thrombus in the IVC and the subsequent thrombus entrapment in the filter were documented during aspiration thrombectomy or Urokinase thrombolysis in four patients. Recurrent thrombus didn't occur during the follow-up period (range:3-20 months) in five of the six patients. In one patient, a recurrent thrombus due to the discontinuance of anticoagulation therapy was identified at the filter detachment site of the IVC on the follow

  14. Thrombus imaging in acute ischaemic stroke using thin-slice unenhanced CT: comparison of conventional sequential CT and helical CT

    International Nuclear Information System (INIS)

    Ahn, Sung Soo; Kim, Eung Yeop

    2012-01-01

    Thin-slice helical unenhanced CT can be used for thrombus imaging but increases radiation exposure. Conventional sequential images obtained by multidetector CT can be reconstructed into thin-slice images. The purpose of this study was to evaluate if conventional sequential unenhanced CT images can replace helical unenhanced CT for thrombus imaging. Fifty consecutive patients with acute ischaemic stroke underwent both 5-mm conventional sequential unenhanced CT and helical unenhanced CT. Each of the sequential and helical unenhanced CT images was subsequently reconstructed into four 1.25-mm images. Thrombus volumes and HU were measured semi-automatically using both types of unenhanced CT. Thrombus HU ratio (rHU) was calculated using the HU of the contralateral segment. The intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess measurement agreement. The mean rHUs were 1.47 ± 0.17 for sequential unenhanced CT and 1.47 ± 0.18 helical unenhanced CT (P = 0.542). The mean thrombus volumes were 124.25 ± 125.65 mm 3 and 117.84 ± 124.32 mm 3 on sequential and helical unenhanced CT images, respectively (P = 0.063). Measurement agreement between thrombus volumes from the two unenhanced CT images was high (ICC = 0.981). Thin-slice unenhanced CT images reconstructed from 5-mm sequential images can replace helical unenhanced CT for thrombus imaging in acute ischaemic stroke. circle Unenhanced CT is used to evaluate intra-arterial thrombus. (orig.)

  15. A floating right heart thrombus in transit across tricuspid valve causing an endocardial friction rub

    Directory of Open Access Journals (Sweden)

    Babu Kanjirakadavath

    2013-07-01

    Full Text Available We report a 42-year-old lady on combined oral contraceptive pills with deep venous thrombosis and mild pulmonary embolism, who developed shock, while being treated with heparin. On auscultation, there was an unexpected loud, superficial, squeaky, triphasic friction rub over the left lower parasternal area. Simultaneous echocardiogram revealed a large serpiginous, freely floating mass in right atrium, prolapsing freely to right ventricular inlet across the tricuspid valve. The endocardial friction rub persisted for about 24 h as long as the thrombus was intracardiac and disappeared when the thrombus disappeared from right heart, occluding the proximal left pulmonary artery. She died due to shock awaiting surgery. We highlight that such a rub in a patient with deep venous thrombosis, though rare, may be an important clue to impending pulmonary embolism.

  16. [Severe blood coagulation disorder as the first sign of a peritoneal hemangio-endothelioma: a new therapeutic approach (author's transl)].

    Science.gov (United States)

    Debray, P; Girot, R; Josso, F; Mselati, J C; Hubert, P; Lavaud, J; Cloup, M

    1980-10-01

    The authors describe a 3 1/2 month old infant with hemangio-endothelioma and a severe blood coagulation disorder. The tumor was inoperable and the severe blood coagulation disorder posed considerable therapeutic problem. After treatment with massive amounts of blood clotting factors, an antifibrinolytic drug and radiotherapy, the child's condition improved.

  17. Multi-parameter assessment of thrombus formation on microspotted arrays of thrombogenic surfaces

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Susanne de Witt, Frauke Swieringa, Judith Cosemans & Johan Heemskerk ### Abstract Thrombus formation by adhering and aggregating blood platelets is fundamental to hemostasis and is a prerequisite for vascular occlusion in pathological thrombosis. The parallel-plate flow chamber technique has been extensively used to measure platelet adhesion and activation in vitro at arterial or venous flow conditions. Here, we describe the use of brightfield and confocal fluorescence micros...

  18. Population based analysis of survival in patients with renal cell carcinoma and venous tumor thrombus.

    Science.gov (United States)

    Whitson, Jared M; Reese, Adam C; Meng, Maxwell V

    2013-02-01

    To identify prognostic factors for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and determine the significance of thrombus level on survival. Patients within the Surveillance, Epidemiology, and End Results (SEER) database with RCC and VTT were identified and included if managed surgically. The Kaplan-Meier method and Cox regression analyses were performed to identify factors associated with disease-specific survival. A total of 1,875 patients met the inclusion criteria. One-year survival for patients undergoing surgery was 60% for patients with metastases and 90% for those without. Factors associated with worse survival included larger tumor size (HR 1.2, 95% CI 1.0-1.4), medullary, collecting duct, or sarcomatoid histology (HR 2.2, 95% CI 1.5-3.3), Fuhrman grade 3 (HR 2.2, 95% CI 1.5-3.3) or grade 4 (HR 2.9, 95% CI 1.8-4.5) tumors, positive lymph nodes (HR 1.5, 95% CI 1.0-2.0), and metastases (HR 3.5, 95% CI 2.6-4.8). Thrombus level above the diaphragm (T3c) was not significantly associated with worse survival (HR 1.4, 95% CI 0.8-2.5). In this large, population-based study of patients with RCC and VTT, we identify several disease-specific factors strongly associated with cancer-specific mortality. After controlling for adverse prognostic factors, thrombus level was not associated with worse outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Relationship between Serum Inflammatory Biomarkers and Thrombus Characteristics in Patients with ST Segment Elevation Myocardial Infarction.

    Science.gov (United States)

    Niccoli, Giampaolo; Menozzi, Alberto; Capodanno, Davide; Trani, Carlo; Sirbu, Vasile; Fineschi, Massimo; Zara, Chiara; Crea, Filippo; Trabattoni, Daniela; Saia, Francesco; Ladich, Elena; Biondi Zoccai, Giuseppe; Attizzani, Guilherme; Guagliumi, Giulio

    2017-01-01

    To compare angiographic and optical coherence tomography (OCT) data pertinent to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with ST elevation myocardial infarction (STEMI) with or without inflammation, as assessed by C-reactive protein (CRP) and myeloperoxidase (MPO). In the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, 140 patients with STEMI referred for primary percutaneous intervention were enrolled. The patients underwent OCT assessment of the culprit vessel, along with blood sampling of CRP and MPO, and histologic analysis of the thrombus. Biomarkers were available for 129 patients, and histology and immunohistochemistry of the thrombi were available for 78 patients. Comparisons were made using the median thresholds of CRP and MPO (2.08 mg/L and 604.124 ng/mL, respectively). There was no correlation between CRP and MPO levels in the whole population (p = 0.685). Patients with high CRP levels had higher thrombus grades and more frequent TIMI flow 0/1 compared with those with low CRP levels (5 [1st quartile 3; 3rd quartile 5] vs. 3.5 mg/L [1; 5], p = 0.007, and 69.3 vs. 48.5%, p = 0.04, respectively). Patients with high MPO levels more commonly had early thrombi than had those with low MPO levels (42.5 vs. 20.0%, p = 0.04). CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, with CRP more related to thrombus burden and MPO to thrombus age. © 2016 S. Karger AG, Basel.

  20. Frequency and Relevance of Acute Peritraumatic Pulmonary Thrombus Diagnosed by Computed Tomographic Imaging in Combat Casualties

    Science.gov (United States)

    2013-08-01

    such as anticoagulation or vena caval interruption. CONCLUSION: This report is the first to characterize acute, peritraumatic pulmonary thrombus in...anticoagulation or vena cava filter devices. (J Trauma Acute Care Surg. 2013;75: S215YS220. Copyright * 2013 by Lippincott Williams & Wilkins) LEVEL OF...traumatic brain, spinal cord, or severe pelvic injury. Certain situations result in the placement of a vena cava filter adding to the risk of com

  1. Renal Angiomyolipoma with Fatty Thrombus Extending to the Right Atrium: An Exceptional Presentation

    Directory of Open Access Journals (Sweden)

    Yassine Nouira

    2013-01-01

    Full Text Available This paper reports the case of 34-year-old woman who presented with bilateral renal angiomyolipomas (AMLs. On the right side, there was a large AML with a fatty thrombus extending to the right atrium. The treatment consisted of right nephrectomy and complete thrombectomy with extracorporeal circulation and right atriotomy. Postoperatively, the patient was septic and died on postoperative day 7 because of septic shock.

  2. SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets.

    Science.gov (United States)

    Kim, Yun Hak; Bae, Jin Ung; Kim, In Suk; Chang, Chulhun L; Oh, Sae Ock; Kim, Chi Dae

    2016-12-01

    SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH 4 Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.

  3. Right Ventricular Thrombus in a 36-Year-Old Man with Factor V Leiden.

    Science.gov (United States)

    Hajsadeghi, Shokoufeh; Naghshin, Roozbeh; Hejrati, Maral; Kerman, Scott Reza Jafarian

    2015-01-01

    Factor V Leiden deficiency is the most common hereditary hypercoagulable disease in the United States and involves 5% of the Caucasian population. Up to 30% of patients who present with deep vein thrombosis (DVT) or pulmonary thromboembolism present with this condition. This is a case report of a 36-year-old man who experienced one episode of DVT within the previous year and was admitted to our hospital due to productive coughs and hemoptysis. Paraclinical studies demonstrated a right ventricular thrombus. Additional investigation was done to find the underlying cause. Laboratory tests were positive for Factor V Leiden mutation. Other factors for hypercoagulability states were normal. Given that Factor V Leiden mutation is a life-threatening condition with a relatively high prevalence and considering its thrombogenesis, screening tests are necessary in young patients without obvious reasons for recurrent thrombus formation. It seems that medical noninvasive treatments can be an alternative therapy to surgery when a ventricular thrombus is suspected in these patients.

  4. Use of an anti-platelet monoclonal antibody F (ab')2 fragment for imaging thrombus

    International Nuclear Information System (INIS)

    Loutfi, I.; Stuttle, A.W.J.; Peters, A.M.; George, P.; Lavender, J.P.; Lumley, P.

    1990-01-01

    Ten patients with suspected thrombus have been studied using 111 In-labelled F (ab')2 fragments of P256, a monoclonal antibody which recognizes an epitope on the platelet membrane glycoprotein IIb/IIIa complex. The F (ab')2 fragment was radiolabelled with 111 In via diethylenetri-aminepentamacetic acid to give a specific activity of up to 190 MBq (5mCi) mg - 1 without impairment of immunoreactivity. In vitro platelet aggregation studies showed that the F (ab')2 fragment caused less platelet aggregation than the whole antibody on a molar ratio and was without significant effect upon the sensitivity of platelets to a range of aggregating agents. Platalets were labelled in ten patients by intravenous injection of approximately 100 μg P256 F (ab')2. Of the ten patients studies, six showed localization of activity consistent with platelet accumulation. Localization was clearly seen when associated with thrombus of the lower limbs (three patients: deep vein thrombosis; one patient: aortofemoral graft), and was apparent although less marked in two other cases, one of aortic aneurysm and one of carotid stenosis. Use of radiolabelled P256 F (ab')2 offers a means of non-invasive detection of thrombus which, from in vitro studies, would appear to have less direct effect of platelet behaviour than the whole antibody. (author). 9 refs. 8 figs. 1 tab

  5. Cathepsin G-dependent modulation of platelet thrombus formation in vivo by blood neutrophils.

    Directory of Open Access Journals (Sweden)

    Nauder Faraday

    Full Text Available Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies.

  6. Retrievable Vena Cava Filters in Major Trauma Patients: Prevalence of Thrombus Within the Filter

    International Nuclear Information System (INIS)

    Mahrer, Arie; Zippel, Douglas; Garniek, Alexander; Golan, Gil; Bensaid, Paul; Simon, Daniel; Rimon, Uri

    2008-01-01

    The purpose of this study was to report the prevalence of thrombus within a retrievable vena cava filter inserted prophylactically in major trauma patients referred for filter extraction. Between November 2002 and August 2005, 80 retrievable inferior vena cava filters (68 Optease and 12 Gunther-Tulip) were inserted into critically injured trauma patients (mean injury severity score 33.5). The filters were inserted within 1 to 6 (mean 2) days of injury. Thirty-seven patients were referred for filter removal (32 with Optease and 5 with Gunther-Tulip). The indwelling time was 7 to 22 (mean 13) days. All patients underwent inferior vena cavography prior to filter removal. There were no insertion-related complications and all filters were successfully deployed. Forty-three (54%) of the 80 patients were not referred for filter removal, as these patients continued to have contraindications to anticoagulation. Thirty-seven patients (46%) were referred for filter removal. In eight of them (22%) a large thrombus was seen within the filters and they were left in place, all with the Optease device. The other 29 filters (36%) were removed uneventfully.We conclude that the relatively high prevalence of intrafilter thrombi with the Optease filter may be explained by either spontaneous thrombus formation or captured emboli.

  7. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    Science.gov (United States)

    2016-12-01

    drug sen- sitivity in cancer cells. Nature 483(7391):570–575. 14. Adams JM, et al. (2005) Subversion of the Bcl-2 life/death switch in cancer de ...SCLC (N=15) other solid tumors (N=229) P= 0.001 Faber et al. Sup. Figure 3 # Cancer type 1 biliary tract 2 bladder 3 breast 4 cervix 5...lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis, Preclinical therapeutics 16. SECURITY

  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. 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.

  10. 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

  11. Alzheimer's Disease Drug Discovery--11th International Conference--Promising New Therapeutic Approaches. 27-28 September 2010, Jersey City, NJ, USA.

    Science.gov (United States)

    Wolfe, Michael S

    2010-12-01

    The 11th Alzheimer's Disease Drug Discovery International Conference, held in Jersey City, NJ, USA, included topics covering new therapeutic developments in the field of Alzheimer's disease. This conference report highlights selected presentations on the use of patient-specific stem cells, and neuroprotection, regeneration and cognitive enhancement strategies for the prevention or treatment of Alzheimer's disease. Investigational approaches discussed include allopregnanolone for neuron protection and regeneration, PDE5 inhibitors as therapeutics, upregulating the protein Klotho to prevent cognitive decline, targeting memory deficits induced by Aβ42 oligomers, inhibiting striatal-enriched protein tyrosine phosphatase (STEP) for treating neuropsychiatric disorders, and agonism of GABA-A receptors to treat age-related cognitive deficits.

  12. Sensitivity of 3D gradient recalled echo susceptibility-weighted imaging technique compared to computed tomography angiography for detection of middle cerebral artery thrombus in acute stroke

    Directory of Open Access Journals (Sweden)

    Amit Agarwal

    2014-11-01

    Full Text Available We aimed at comparing the sensitivity of magnetic resonance (MR susceptibility-weighted imaging (SWI with computed tomography angiography (CTA in the detection of middle cerebral artery (MCA thrombus in acute stroke. Seventy-nine patients with acute MCA stroke was selected using our search engine software; only the ones showing restricted diffusion in the MCA territory on diffusion-weighted images were included. We finally selected 35 patients who had done both MRI (including SWI and CTA. Twenty random subjects with completely normal MRI (including SWI exam were selected as control. Two neuroradiologists (blinded to the presence or absence of stroke reviewed the SW images and then compared the findings with CT angiogram (in patients with stroke. The number of MCA segments showing thrombus in each patient was tabulated to estimate the thrombus burden. Thrombus was detected on SWI in one or more MCA segments in 30 out of 35 patients, on the first review. Of the 30, SWI showed thrombus in more than one MCA segments in 7 patients. CTA depicted branch occlusion in 31 cases. Thrombus was seen on both SWI and CTA in 28 patients. Thrombus was noted in two patients on SWI only, with no corresponding abnormality seen on CTA. Two patients with acute MCA showed no vascular occlusion or thrombus on either CTA or SWI. Only two case of false-positive thrombus was reported in normal control subjects. Susceptibility-weighted images had sensitivity and specificity of 86% and 90% respectively, with positive predictive value 94%. Sensitivity was 86% for SWI, compared with 89% for CTA, and this difference was statistically insignificant (P>0.05. Of all the positive cases on CTA (31 corresponding thrombus was seen on SWI in 90% of subjects (28 of 31. Susceptibility-weighted imaging has high sensitivity for detection of thrombus in acute MCA stroke. Moreover, SWI is a powerful technique for estimation of thrombus burden, which can be challenging on CTA.

  13. Incremental Value of Three-Dimensional Transesophageal Echocardiography over the Two-Dimensional Technique in the Assessment of a Thrombus in Transit through a Patent Foramen Ovale.

    Science.gov (United States)

    Thind, Munveer; Ahmed, Mustafa I; Gok, Gulay; Joson, Marisa; Elsayed, Mahmoud; Tuck, Benjamin C; Townsley, Matthew M; Klas, Berthold; McGiffin, David C; Nanda, Navin C

    2015-05-01

    We report a case of a right atrial thrombus traversing a patent foramen ovale into the left atrium, where three-dimensional transesophageal echocardiography provided considerable incremental value over two-dimensional transesophageal echocardiography in its assessment. As well as allowing us to better spatially characterize the thrombus, three-dimensional transesophageal echocardiography provided a more quantitative assessment through estimation of total thrombus burden. © 2015, Wiley Periodicals, Inc.

  14. 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.

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

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

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

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

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

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

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

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

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

  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. Mechanisms linking depression co-morbid with obesity: An approach for serotonergic type 3 receptor antagonist as novel therapeutic intervention.

    Science.gov (United States)

    Kurhe, Yeshwant; Mahesh, Radhakrishnan

    2015-10-01

    Despite of the enormous research, therapeutic treatment for depression has always been a serious issue. Even though depression and obesity are individual abnormal health conditions, each act as a triggering factor for the other. Obese individuals are twice prone to develop depression than that of non-obese persons. The exact mechanism how obesity increases the risk for depression still remains an area of interest for research in neuropsychopharmacology. Depression and obesity share some common pathological pathways such as hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, dysregulation of oxidant/antioxidant system balance, higher level of inflammatory cytokines, leptin resistance, altered plasma glucose, insulin resistance, reduced neuronal brain derived neurotrophic factor (BDNF) and decreased serotonergic neurotransmission in various regions of brain. The antidepressant-like effect of 5-HT3 receptor antagonists through allosteric modulation of serotonergic pathways is well evident from several research investigations belonging to our and some in other laboratories. Furthermore, serotonin regulates diet intake, leptin, corticosterone, inflammatory mechanisms, altered plasma glucose, insulin resistance and BDNF concentration in brain. The present review deals with various biological mechanisms involved in depression co-morbid with obesity and 5-HT3 receptor antagonists by modulation of serotonergic system as a therapeutic target for such co-morbid disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Effect of Adjunctive Thrombus Aspiration on In-Hospital and 3-Year Outcomes in Patients With ST-Segment Elevation Myocardial Infarction and Large Native Coronary Artery Thrombus Burden.

    Science.gov (United States)

    Keskin, Muhammed; Kaya, Adnan; Tatlısu, Mustafa Adem; Uzman, Osman; Börklü, Edibe Betül; Çinier, Göksel; Tekkeşin, Ahmet İlker; Türkkan, Ceyhan; Hayıroğlu, Mert İlker; Kozan, Ömer

    2017-11-15

    Although the long-term clinical benefit of adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) remains controversial, the impact of TA in patients with large thrombus has not been evaluated. The aim of the present study was to investigate the effect of adjunctive TA during PPCI on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and a large thrombus. We assessed the effect of adjunctive TA on in-hospital and 3-year clinical outcomes in 627 patients with STEMI and a large thrombus in the native coronary artery. The cumulative 3-year incidence of all-cause death was not significantly different between the 2 groups (91.5% vs 89.0%, log-rank test p = 0.347). After adjusting for confounders, the risk of all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio 1.11, 95% confidence interval 0.60 to 3.54, p = 0.674). The adjusted risks of target lesion revascularization, nonfatal acute myocardial infarction, and stent thrombosis were also not significantly different between the 2 groups. In conclusion, adjunctive TA during PPCI was not associated with better in-hospital and 3-year all-cause deaths in patients with STEMI and a large coronary artery thrombus. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Bisiani, Leah; Angus, Jocelyn

    2013-07-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  4. 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.)

  5. Multi-targeted molecular therapeutic approach in aggressive neuroblastoma: the effect of Focal Adhesion Kinase-Src-Paxillin system.

    Science.gov (United States)

    Kratimenos, Panagiotis; Koutroulis, Ioannis; Marconi, Dante; Syriopoulou, Vasiliki; Delivoria-Papadopoulos, Maria; Chrousos, George P; Theocharis, Stamatios

    2014-12-01

    Nonreceptor tyrosine kinases play key roles in the integrin system. Located at the focal adhesions, they consist of large protein complexes through which the cytoskeleton connects to the extracellular matrix. The focal adhesion kinase (FAK)-Src-paxillin complex, a major mediator of the integrin pathway, contributes to cell migration and motility. Its overexpression is increased in children with advanced neuroblastoma (NB), one of the most common malignancies of childhood, with poor survival. We review the most recent data on FAK-Src-paxillin and their implications in NB, the molecular structure and the regulatory mechanisms of each molecule and their interactions and up-to-date information on their use as the newest biomarkers and their potential use as therapeutic targets in NB. Based on the current literature, we hypothesize that combined and concurrent inhibition of the FAK-Src-Paxillin system may result in significant tumor suppression and prevention or delay of metastasis.

  6. Nanotechnological advances for cutaneous release of tretinoin: an approach to minimize side effects and improve therapeutic efficacy.

    Science.gov (United States)

    Raminelli, Ana Claudia Pompeu; Romero, Valeria; Semreen, Mohammad H; Leonardi, Gislaine Ricci

    2018-03-12

    The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Herein we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2009-01-01

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

  8. Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

    Science.gov (United States)

    Luther, Natascha; Shahneh, Fatemeh; Brähler, Melanie; Krebs, Franziska; Jäckel, Sven; Subramaniam, Saravanan; Stanger, Christian; Schönfelder, Tanja; Kleis-Fischer, Bettina; Reinhardt, Christoph; Probst, Hans Christian; Wenzel, Philip; Schäfer, Katrin; Becker, Christian

    2016-12-09

    Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (T EM ) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited T EM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4 + and CD8 + T EM cells. Reducing the number of T EM cells through a depletion recovery procedure, we show that intravenous T EM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution. © 2016 American Heart Association, Inc.

  9. 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...

  10. 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...

  11. Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute Exercise.

    Science.gov (United States)

    Przyborowski, Kamil; Proniewski, Bartosz; Czarny, Joanna; Smeda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Zoladz, Jerzy A; Chlopicki, Stefan

    2018-02-21

    An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (O2) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of O2 in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. An acute bout of strenuous exercise in mice reduced NO and in parallel increased O2 production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased O2 production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice.

  12. Late thrombosis of a mitral bioprosthetic valve with associated massive left atrial thrombus

    Directory of Open Access Journals (Sweden)

    Preetham R Muskula

    2017-04-01

    Full Text Available An 84-year-old man presented 5 years after bioprosthetic mitral valve replacement with three months of worsening dyspnea on exertion. A new mitral stenosis murmur was noted on physical examination, and an electrocardiogram revealed newly recognized atrial fibrillation. Severe mitral stenosis (mean gradient = 13 mmHg was confirmed by transthoracic echocardiography. Transesophageal echocardiography revealed markedly thickened mitral bioprosthetic leaflets with limited mobility, and a massive left atrial thrombus (>4 cm in diameter (Fig. 1A, B, C, D and Videos 1, 2, 3 and 4. Intravenous heparin was initiated, and 5 days later, he was taken to the operating room for planned redo mitral valve replacement and left atrial thrombus extraction. Intraoperative transesophageal echocardiography revealed near-complete resolution of the bioprosthetic leaflet thickening, and a mean mitral gradient of only 3 mmHg (Fig. 2A, B, C and Videos 5, 6 and 7. The patient underwent resection of the massive left atrial thrombus (Fig. 2D but did not require redo mitral valve replacement. He was initiated on heparin (and transitioned to warfarin early in the post-operative period, with complete resolution of dyspnea on exertion at 3-month follow-up. Bioprosthetic valve thrombosis is increasingly recognized as a cause of early prosthetic valve dysfunction (1, 2. This case illustrates that bioprosthetic valve thrombosis may occur years after valve replacement; therefore, any deterioration in a patient’s clinical status (new-onset dyspnea, heart failure or atrial fibrillation warrants a thorough evaluation of the bioprosthetic valve with transesophageal echocardiography. In this case, initiation of anticoagulation obviated the need for redo mitral valve replacement.

  13. Complete Resolution of a Large Bicuspid Aortic Valve Thrombus with Anticoagulation in Primary Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    Rayan Jo Rachwan

    2017-09-01

    Full Text Available Native aortic valve thrombosis in primary antiphospholipid syndrome (APLS is a rare entity. We describe a 38-year-old man who presented with neurological symptoms and a cardiac murmur. Transthoracic echocardiography detected a large bicuspid aortic valve thrombus. Laboratory evaluation showed the presence of antiphospholipid antibodies. Anticoagulation was started, and serial echocardiographic studies showed complete resolution of the aortic valve vegetation after 4 months. The patient improved clinically and had no residual symptoms. This report and review of the literature suggests that vegetations in APLS can be treated successfully with conservative treatment, regardless of their size.

  14. Epithelioid angiomyolipoma with involvement of inferior vena cava as a tumor thrombus: A case report

    Directory of Open Access Journals (Sweden)

    Deyi Luo

    2011-02-01

    Full Text Available A 27-year-old female with chronic right-side flank pain was diagnosed with renal epithelioid angiomyolipoma (EAML extending as a thrombus into the renal vein and vena cava. Intravascular extension of EAML is quite rare; however, it may result in fatal complications if not appropriately treated. She successfully underwent a radical nephrectomy and inferior vena caval thrombectomy. Intravascular extension of EAML, although rare, has been reported. We present a new case and a description of the surgical management. Furthermore, we reviewed and analyzed nine case reports of invasive renal EAMLs.

  15. Free Floating Thrombus in Carotid Artery in a Patient with Recurrent Strokes

    Directory of Open Access Journals (Sweden)

    Moni Roy

    2017-01-01

    Full Text Available We present a case of 72-year-old male with reported past medical history of recurrent transient ischemic attacks (TIAs presenting with myriad of neurological symptoms. Patient was transferred from outlying hospital with complaints of right sided facial droop and dysarthria. Computed tomography angiography (CTA showed high grade proximal left internal carotid artery (ICA stenosis along with interesting finding of a free floating thrombus (FFT in the left ICA. After discussion with the neurosurgical team, our case was treated conservatively with combination of antiplatelet therapy with Aspirin and anticoagulation with Warfarin without recurrence of TIAs or strokes on six-month follow-up.

  16. Aneurysmal dilatation of persistent vitelline vein with thrombus in a neonate

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Kun Woo; Sung, Deuk Jae; Park, Beom Jin; Kim, Min Ju; Cho, Sung Bum [Korea University College of Medicine, Department of Radiology, Anam Hospital, Seoul (Korea, Republic of)

    2014-07-15

    The paired vitelline veins selectively involute and form a part of the portal vein during embryonic development. The presence of a persistent vitelline vein segment after birth is very rare and can be confused with anomalies of the portal and umbilical veins. We present sonographic, CT and MRI findings of aneurysmal dilatation of a persistent vitelline vein with thrombus in a neonate; this case was first misdiagnosed as an umbilical vein varix by prenatal US. MRI was used to identify the persistent vitelline vein segment and the remnant umbilical vein segment. (orig.)

  17. 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.

  18. 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

  19. New therapeutic approaches in the treatment of anogenital lichen sclerosus: does photodynamic therapy represent a novel option?

    Science.gov (United States)

    Criscuolo, Anna A; Schipani, Caterina; Cannizzaro, Maria V; Messinese, Serena; Chimenti, Sergio; Piccione, Emilio; Saraceno, Rosita

    2017-04-01

    Lichen sclerosus et atrophicus (LSA) is an inflammatory, mucocutaneous disorder that affects male and especially female with a debilitating impact on the quality of life. Common localization is the anogenital area. If not treated LSA can leave scars, functional impairment and can evolve in squamous cell carcinoma. The first line of treatment is represented by topical, ultra-potent corticosteroids, but often patients are unresponsive; moreover this therapy is frequently associated to relapses of the disease after discontinuation. In this prospective observational study, the efficacy of three different treatments - topical calcineurin inhibitors, avocado and soya beans extracts, and methyl aminolevulinate photodynamic therapy (MAL-PDT) - was evaluated, and an effort has been made to define a therapeutic algorithm according to the severity of the disease. Of the 150 patients who were referred to the outpatient clinic for a dermatological and gynecological visit, 33 met the inclusion criteria. Sixteen (88%) patients showed an improvement of the lesion and a reduction of the itch; 3 (16.7%) patients with sever itch and fissurated lesions were evaluated for the MAL-PDT therapy. A total of 9 patients, after accurate examination of the lesions, were treated with MAL-PDT. The totality of the patients experienced a resolution of the lesions. In the early stages the use of ASE can represent a valid alternative that is well tolerated by the patients reducing the itching, dryness and improving the mucosal texture. The use of MAL-PDT represents a valid treatment in the moderate-severe stages of LSA.

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

    Science.gov (United States)

    Thevis, Mario; Schänzer, Wilhelm

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Jun eWang

    2014-03-01

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

  2. Lessons from genetics: is it time to revise the therapeutic approach to children with steroid-resistant nephrotic syndrome?

    Science.gov (United States)

    Becherucci, Francesca; Mazzinghi, Benedetta; Provenzano, Aldesia; Murer, Luisa; Giglio, Sabrina; Romagnani, Paola

    2016-08-01

    Primitive nephrotic syndrome is one of the most common glomerular diseases in childhood and represents the clinical manifestation of various pathologic changes in the kidney. In children, nephrotic syndrome is classified based on the initial response to empiric corticosteroid treatment, which is considered as the best predictor of patients' final outcome. The advent of next-generation sequencing technology showed that genetic alterations in structural genes of the podocyte can be recognized in a significant proportion of not only familial or syndromic patients with steroid-resistant nephrotic syndrome (SRNS), but also of sporadic cases, raising the question of whether it is time to update current protocols of patient care. In this review, we discuss the implications derived from several studies describing a high prevalence in children with SRNS of pathogenic mutations in a group of genes and their unresponsiveness to immunosuppressive therapy. We propose a diagnostic and therapeutic algorithm to reduce the exposure to immunosuppressants in individuals with unresponsive forms of the disease, sparing patients the untoward side effects of prolonged ineffective treatments, and at the same time guaranteeing the optimal immunosuppressive or other new therapy in potentially responsive patients.

  3. Development of an Optical Detector of Thrombus Formation on the Pivot Bearing of a Rotary Blood Pump.

    Science.gov (United States)

    Sakota, Daisuke; Fujiwara, Tatsuki; Ouchi, Katsuhiro; Kuwana, Katsuyuki; Yamazaki, Hiroyuki; Maruyama, Osamu

    2016-09-01

    Continuous optical monitoring of thrombus formation in extracorporeal mechanical circulatory support (EMCS) devices will contribute to safe, long-term EMCS. A clinically applicable optical detector must be able to distinguish among the optical characteristics of oxygen saturation (SaO2 ), hematocrit (Hct), and thrombus formation. In vitro studies of spectral changes at wavelengths from 400 to 900 nm associated with SaO2 , Hct, and thrombus formed around the top pivot bearing of a Gyro C1E3 pump were conducted. Fresh porcine blood anticoagulated with sodium citrate was circulated in a mock circuit using the pump. The SaO2 , Hct, and anticoagulation activity were altered using an oxygenator, autologous plasma, and calcium chlorite injection, respectively. Light from a xenon lamp was guided by an incident fiber perpendicularly fixed on the top bearing. This light was scattered by blood pooled between the male and female pivots. The detection fiber was perpendicularly fixed against the incident fiber, and the side-scattered light was detected and guided to a spectrophotometer. As a result, light at two different wavelengths, 420 and 810 nm, was identified as suitable for thrombus detection because it was negligibly influenced by SaO2 and was able to detect the optical characteristics of fibrin. The light at these two wavelengths responded more quickly to thrombus formation than the inlet or outlet pressure, and flow rate change. The optical changes showed the changes in Hct around the top pivot bearing, which is caused by the reduction in density of fibrin-trapped red blood cells (RBCs) due to the RBCs being swept away by the surrounding blood flow. The proposed method was also able to detect fibrin production by extracting subtle differences in the optical characteristics between the Hct and thrombus formation. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Development of Thrombus in a Systemic Vein after Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimatsu, Rika; Yamagami, Takuji; Tanaka, Osamu; Miura, Hiroshi; Nishimura, Tsunehiko [Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Okuda, Kotaro; Hashiba, Mitsuoki [Fukuchiyama City Hospital, Kyoto (Japan)

    2012-06-15

    To retrospectively evaluate the frequency and risk factors for developing thrombus in a systemic vein such as the infrarenal inferior vena cava or the iliac vein, in which a balloon-occluded retrograde transvenous obliteration (B-RTO) catheter was indwelled. Forty-nine patients who underwent B-RTO for gastric varices were included in this study. The B-RTO procedure was performed from the right femoral vein, and the B-RTO catheter was retained overnight in all patients. Pre- and post-procedural CT scans were retrospectively compared in order to evaluate the development of thrombus in the systemic vein in which the catheter was indwelled. Additionally, several variables were analyzed to assess risk factors for thrombus in a systemic vein. In all 49 patients (100%), B-RTO was technically successful, and in 46 patients (94%), complete thrombosis of the gastric varices was achieved. In 6 patients (12%), thrombus developed in the infrarenal inferior vena cava or the right common-external iliac vein. All thrombi lay longitudinally on the right side of the inferior vena cava or the right iliac vein. One of the aforementioned 6 patients required anticoagulation therapy. No symptoms suggestive of pulmonary embolism were observed. Prothrombin time-international normalized ratio and the addition of 5% ethanolamine oleate iopamidol, on the second day, were related to the development of thrombus. Development of a thrombus in a systemic vein such as the inferior vena cava or iliac vein, caused by indwelling of the B-RTO catheter, is relatively frequent. Physicians should be aware of the possibility of pulmonary embolism due to iliocaval thrombosis.

  5. 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.

  6. 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.

  7. Targeting AMP-activated protein kinase as a novel therapeutic approach for the treatment of metabolic disorders.

    Science.gov (United States)

    Viollet, B; Mounier, R; Leclerc, J; Yazigi, A; Foretz, M; Andreelli, F

    2007-12-01

    effects provide the rationale for the development of new therapeutic strategies in metabolic disorders.

  8. Afatinib is a new therapeutic approach in chordoma with a unique ability to target EGFR and Brachyury.

    Science.gov (United States)

    Magnaghi, Paola; Salom, Barbara; Cozzi, Liviana; Amboldi, Nadia; Ballinari, Dario; Tamborini, Elena; Gasparri, Fabio; Montagnoli, Alessia; Raddrizzani, Laura; Somaschini, Alessio; Bosotti, Roberta; Orrenius, Christian; Bozzi, Fabio; Pilotti, Silvana; Galvani, Arturo; Sommer, Josh; Stacchiotti, Silvia; Isacchi, Antonella

    2017-12-13

    Chordomas are rare bone tumors with no approved therapy. These tumors express several activated tyrosine kinase receptors, which prompted attempts to treat patients with tyrosine kinase inhibitors. Although clinical benefit was observed in Phase II clinical trials with imatinib and sorafenib, and sporadically also with EGFR inhibitors, therapies evaluated to date have shown modest activity. With the goal of identifying new drugs with immediate therapeutic potential for chordoma patients, we collected clinically approved drugs and other advanced inhibitors of MET, PDGFRβ and EGFR tyrosine kinases, and assessed their anti-proliferative activity against a panel of chordoma cell lines. Chordoma cell lines were not responsive to MET and PDGFRβ inhibitors. U-CH1 and UM-Chor1 were sensitive to all EGFR inhibitors, while the remaining cell lines were generally insensitive to these drugs. Afatinib was the only EGFR inhibitor with activity across the chordoma panel. We then investigated the molecular mechanisms behind the responses observed and found that the anti-proliferative IC50s correlate with the unique ability of afatinib to promote degradation of EGFR and brachyury, an embryonic transcription factor considered a key driver of chordoma. Afatinib displayed potent antitumor efficacy in U-CH1, SF8894, CF322 and CF365 chordoma tumor models in vivo. In the panel analyzed, high EGFR phosphorylation and low AXL and STK33 expression correlated with higher sensitivity to afatinib and deserve further investigation as potential biomarkers of response. These data support the use of afatinib in clinical trials and provide the rationale for the upcoming European phase II study on afatinib in advanced chordoma. Copyright ©2017, American Association for Cancer Research.

  9. 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

  10. Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach?

    Science.gov (United States)

    Dunleavy, Kieron; Wilson, Wyndham H

    2015-01-01

    Primary mediastinal B-cell lymphoma (PMBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that is putatively derived from a thymic B cell. Accounting for up to 10% of cases of DLBCL, this subtype predominantly affects women in the third and fourth decades of life. Its clinical and molecular characteristics are distinct from other subtypes of DLBCL and, in fact, closely resemble those of nodular sclerosing Hodgkin lymphoma (NSHL). Recently, mediastinal lymphomas with features intermediate between PMBL and NSHL, called mediastinal gray-zone lymphomas, have been described. The optimal management of PMBL is controversial, and most standard approaches include a combination of immunochemotherapy and mediastinal radiation. Recently, the recognition that mediastinal radiation is associated with significant long-term toxicities has led to the development of novel approaches for PMBL that have shown excellent efficacy and challenge the need for routine mediastinal radiation.

  11. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review.

    Science.gov (United States)

    Malik, Shahbaz A; Malik, Sarah; Dowsley, Taylor F; Singh, Balwinder

    2015-01-01

    A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus.

  12. ST Elevation Infarction after Heart Transplantation Induced by Coronary Spasms and Mural Thrombus Detected by Optical Coherence Tomography

    DEFF Research Database (Denmark)

    Clemmensen, Tor Skibsted; Holm, Niels Ramsing; Eiskjær, Hans

    2016-01-01

    The case illustrates the possible link between coronary spasms, intraluminal thrombus formation, and widespread organized and layered thrombi in HTx patients. Furthermore, the case underlines the clinical value of OCT as a novel method for high-resolution vessel imaging in heart-transplanted (HTx......, and the left anterior descending coronary artery. The patient was stabilized after percutaneous coronary intervention. As a mural thrombus often goes undetected by coronary angiography, OCT may prove benefit in HTx patients with myocardial infarction or suspected coronary spasms....

  13. Risk factors for development of left ventricular thrombus after first acute anterior myocardial infarction-association with anticardiolipin antibodies

    Directory of Open Access Journals (Sweden)

    Okuyan Ertuğrul

    2010-09-01

    Full Text Available Abstract Background Left ventricular thrombus(LVT] formation is a frequent complication in patients with acute anterior myocardial infarction(MI. LVT is associated with increased risk of embolism and higher mortality rates after acute MI. Anticardiolipin antibodies (ACA are immunoglobulins that react with phospholipid-binding proteins interfering with the prothrombin activator complex. The effects of phospholipids on pathophysiology of cardiovascular thrombotic events are well known. In this study, we aimed to evaluate the importance of clinical and biochemical parameters including anticardiolipin antibodies on left ventricular thrombus formation after acute anterior MI. Methods and Results Seventy patients with a first anterior AMI were prospectively and consecutively enrolled. Patients with previous MI, autoimmune disease, collagen vascular disease and arterial or venous thrombosis history were excluded from this study. At the time of hospitalization, key demographic and clinical characteristics were collected including age, gender, ethanol intake and presence of traditional risk factors for atherosclerosis (hypertension, diabetes, smoking, hyperlipidemia, positive family history. Patients were evaluated for echocardiographic data, blood chemistry and ACA. Two-dimensional and Doppler echocardiographic examinations were performed in all patients within the first week and at 14 days after MI. LV thrombus was detected in 30 (42.8% patients. ACA IgM levels were significantly higher in the patient group with LV thrombus than in the group without thrombus (12.44 ±4.12 vs. 7.69 ± 4.25 mpl, p = 0,01. ACA IgG levels were also found higher in the group with LV thrombus (24.2 ± 7.5 vs.17.98 ± 6.45 gpl, p = 0.02. Multivariate analyses revealed diabetes mellitus, higher WMSI, lower MDT and higher ACA IgM and higher ACA IgG levels as independent predictors of left ventricular thrombus formation. Conclusions Our data demonstrate that beside the low

  14. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review

    Directory of Open Access Journals (Sweden)

    Shahbaz A. Malik

    2015-01-01

    Full Text Available A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient’s workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus.

  15. Extract of Ulmus macrocarpa Hance prevents thrombus formation through antiplatelet activity.

    Science.gov (United States)

    Yang, Won-Kyung; Lee, Jung-Jin; Sung, Yoon-Young; Kim, Dong-Seon; Myung, Chang-Seon; Kim, Ho Kyoung

    2013-09-01

    Ulmus macrocarpa Hance (Ulmaceae) has been used as a traditional oriental medicine for the treatment of edema, mastitis, gastric cancer and inflammation. The aim of this study was to investigate the effects of Ulmus macrocarpa extract (UME) on thrombus formation in vivo, platelet activation ex vivo and fibrinolytic activity in vitro. To identify the antithrombotic activity of UME in vivo, we used an arterial thrombosis model. UME delayed the occlusion time by 13.4 and 13.9 min at doses of 300 and 600 mg/kg, respectively. UME significantly inhibited ex vivo platelet aggregation induced by collagen and adenosine 5'-diphosphate (ADP), respectively, but did not affect the coagulation times following activated partial thromboplastin and prothrombin activation. Therefore, to investigate the antiplatelet effect of UME, the effect of UME on collagen and ADP-induced platelet aggregation in vitro was examined. UME exhibited antiplatelet aggregation activity, induced by ADP and collagen. Furthermore, the fibrinolytic activity of UME was investigated. The results showed that UME significantly increased fibrinolysis at 1,000 mg/ml. In conclusion, the results suggested that UME may significantly inhibit artery thrombus formation in vivo, potentially due to antiplatelet activity, and also exhibits potential as a clot‑dissolving agent for thrombolytic therapy.

  16. Dual inhibition of PI3K and mTOR by VS-5584 suppresses thrombus formation.

    Science.gov (United States)

    Später, Thomas; Müller, Isabelle; Eichler, Hermann; Menger, Michael D; Laschke, Matthias W; Ampofo, Emmanuel

    2017-05-15

    VS-5584 is a highly selective dual kinase inhibitor which suppresses phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) activity. Because these kinases are crucially involved in primary hemostasis, we herein investigated the effect of this compound on thrombus formation in vitro and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP) with VS-5584 inhibited the agonist-induced activation of surface glycoprotein complex (GP)IIb/IIIa and the upregulation of P-selectin. This was associated with a significantly reduced formation of platelet-leukocyte aggregates (PLA). VS-5584 further attenuated platelet aggregation and adhesion after agonist stimulation. In contrast, endothelial expression of intercellular adhesion molecule (ICAM)-1 and vascular cellular adhesion molecule (VCAM)-1 and secretion of von Willebrand Factor (vWF) were not affected by the dual kinase inhibitor. In vivo, VS-5584 inhibited photochemically induced thrombus formation as shown by a significantly prolonged time to complete vessel occlusion when compared to vehicle-treated controls. This was associated with an elevated tail vein bleeding time, indicating a potential hemorrhagic risk in VS-5584-treated mice. Taken together, these novel findings demonstrate that VS-5584 is a potent inhibitor of primary hemostasis targeting multiple platelet functions.

  17. White thrombus formation in blood tubing lines in a chronic hemodialysis unit.

    Science.gov (United States)

    Watnick, Suzanne; Stooksbury, Michael; Winter, Rolf; Riscoe, Michael; Cohen, David M

    2008-03-01

    Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments. Design setting, participants, & measurements: This investigation occurred at the Portland Veterans Administration Medical Center (PVAMC) Hemodialysis Unit from October 2006 through April 2007. Sixty-eight variables regarding demographics, medical history and dialysis treatments were collected on our 34 chronic hemodialysis outpatients. Over a 5-wk interval, 62% (21 of 34) of the chronic hemodialysis patients unexpectedly developed a white precipitate adhering to the lumenal surface of their dialysis blood tubing, with 73 of 580 chronic dialysis treatments exhibiting the phenomenon. Microscopic and biochemical analyses were consistent with white thrombus, formed by an aggregation of platelets and fibrin. An alert was issued and other in-center hemodialysis units noted similar findings. This was remedied by the removal of specific tubing. Both patient-specific and tubing-specific factors may have been operative. Although patient safety was not adversely affected, assessment of clinical and manufacturing variables potentially affecting platelet activation is warranted.

  18. Organizing Thrombus Mimicking a Cardiac Tumor Located at the Mitral-Aortic Intervalvular Fibrosa

    Directory of Open Access Journals (Sweden)

    Ji Seong Lee

    2016-02-01

    Full Text Available Thrombosis at the left ventricular outflow tract occurs without any detectable heart disease or predisposing factors only extremely rarely. A 48-year-old male visited Konkuk University Medical Center with loss of consciousness one month prior to presentation. Before he visited our hospital, he had been diagnosed with a cardiac tumor, which was located between the left atrium and posterior aortic root, and which was adjacent to both the aortic and mitral valves. Cardiac transplantation was recommended at the other hospital because of the high risk of cardiac dysfunction induced by both aortic and mitral valvular dysfunction after surgical resection. Based on preoperative transthoracic echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, and intraoperative transesophageal echocardiography, we considered it to be a benign tumor. Complete resection was achieved and the pathology confirmed organizing thrombus. We report a case of organizing thrombus mimicking a cardiac tumor, which was located at the mitral-aortic intervalvular fibrosa of the left ventricular outflow tract without any heart disease.

  19. Large apical thrombus in a patient with persistent heart failure and hypereosinophilia: Löffler endocarditis.

    Science.gov (United States)

    Cincin, A Altug; Ozben, Beste; Tanrikulu, M Azra; Baskan, Ozdil; Agirbasli, Mehmet

    2008-10-01

    Idiopathic hypereosinophilic syndrome is an uncommon leukoproliferative systemic disorder characterized by the overproduction of eosinophils and poor prognosis. A major source of morbidity and mortality of this syndrome is the associated cardiac involvement represented by endocardial thickening and mural thrombi. We report a 64-year-old woman with persistent symptoms of heart failure despite standard medical therapy. Echocardiography revealed reduced left ventricular filling due to a large apical mass; an abnormal diastolic filling pattern was also noticed. Complete blood count revealed remarkable hypereosinophilia. Cardiac magnetic resonance imaging demonstrated an apical thrombus and intense linear enhancement of the endocardium, which were compatible with Löffler endocarditis. Medical therapy, including corticosteroids and anticoagulation, was initiated promptly. The symptoms improved as the peripheral hypereosinophilia resolved in 15 days. The patient was asymptomatic at the 1-year follow-up visit with complete regression of the apical thrombus and no evidence of restrictive cardiomyopathy. We report this case to draw attention to this particularly rare condition with poor prognosis since quick and accurate diagnosis and prompt initiation of therapy may improve symptoms and survival.

  20. Segmentation, Reconstruction, and Analysis of Blood Thrombus Formation in 3D 2-Photon Microscopy Images

    Directory of Open Access Journals (Sweden)

    Xu Zhiliang

    2010-01-01

    Full Text Available We study the problem of segmenting, reconstructing, and analyzing the structure growth of thrombi (clots in blood vessels in vivo based on 2-photon microscopic image data. First, we develop an algorithm for segmenting clots in 3D microscopic images based on density-based clustering and methods for dealing with imaging artifacts. Next, we apply the union-of-balls (or alpha-shape algorithm to reconstruct the boundary of clots in 3D. Finally, we perform experimental studies and analysis on the reconstructed clots and obtain quantitative data of thrombus growth and structures. We conduct experiments on laser-induced injuries in vessels of two types of mice (the wild type and the type with low levels of coagulation factor VII and analyze and compare the developing clot structures based on their reconstructed clots from image data. The results we obtain are of biomedical significance. Our quantitative analysis of the clot composition leads to better understanding of the thrombus development, and is valuable to the modeling and verification of computational simulation of thrombogenesis.

  1. Tumor thrombus

    DEFF Research Database (Denmark)

    Ravina, Mudalsha; Hess, Søren; Chauhan, Mahesh Singh

    2014-01-01

    period at the Army Hospital Research and Referral in New Delhi, India, and included all oncology cases with FDG-avid thrombosis in the report. The diagnosis of TT was based on FDG-avid solid masses inside the vessels in patients with known malignancy. The SUVmax was calculated. RESULTS: Twenty...

  2. 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.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

  5. 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

  6. 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

  7. 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

  8. 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] 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 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 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

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

    Science.gov (United States)

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

    2009-11-01

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

  10. Tumor cell-protective catalase as a novel target for rational therapeutic approaches based on specific intercellular ROS signaling.

    Science.gov (United States)

    Bauer, Georg

    2012-07-01

    Reactive oxygen species (ROS) exhibit procarcinogenic effects at multiple stages during multistep oncogenesis. As a hallmark of the transformed state, extracellular superoxide anions generated by NADPH oxidase1 (NOX1) are centrally involved in the control of the transformed state. These pro-carcinogenic effects of ROS are counterbalanced by specific ROS-dependent apoptosis induction in malignant cells, based on four interconnected signaling pathways. Tumor progression selects for a phenotype characterized by resistance to ROS-dependent apoptotic signaling. Resistance is based on membrane-associated catalase in tumor cells, which therefore represents a promising and unique target for specific tumor therapy. Novel approache, developed in vitro, utilize antibody-mediated inhibition of catalase or ROS-driven singlet oxygen generation and subsequent inactivation of tumor cell catalase as initial steps. As a consecutive step, malignant cell-generated superoxide anions then drive apoptotic signaling with high selectivity for malignant cells. We propose to translate this complex but well-established ROS-dependent signaling chemistry into novel approaches for experimental therapy in vivo.

  11. 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.

  12. 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.

  13. 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

  14. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    DEFF Research Database (Denmark)

    Ali, Amjad; Naz, Anam; Soares, Siomar C.

    2015-01-01

    Helicobacter pylori is a human gastric pathogen implicated as the major cause of peptic ulcer and second leading cause of gastric cancer (similar to 70%) around the world. Conversely, an increased resistance to antibiotics and hindrances in the development of vaccines against H. pylori are observed......-genome approach; the predicted conserved gene families (1,193) constitute similar to 77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost...... homolog proteins were characterized as universal therapeutic targets against H. pylori based on their functional annotation and protein-protein interaction. Finally, pathogenomics and genome plasticity analysis revealed 3 highly conserved and 2 highly variable putative pathogenicity islands in all...

  15. 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

  16. Nonlinear optical collagen cross-linking and mechanical stiffening: a possible photodynamic therapeutic approach to treating corneal ectasia

    Science.gov (United States)

    Chai, Dongyul; Juhasz, Tibor; Brown, Donald J.; Jester, James V.

    2013-03-01

    In this study we test the hypothesis that nonlinear optical (NLO) multiphoton photoactivation of riboflavin using a focused femtosecond (FS) laser light can be used to induce cross-linking (CXL) and mechanically stiffen collagen as a potential clinical therapy for the treatment of keratoconus and corneal ectasia. Riboflavin-soaked, compressed collagen hydrogels are cross-linked using a FS laser tuned to 760 nm and set to either 100 mW (NLO CXL I) or 150 mW (NLO CXL II) of laser power. FS pulses are focused into the hydrogel using a 0.75 NA objective lens, and the hydrogel is three-dimensionally scanned. Measurement of hydrogel stiffness by indentation testing show that the calculated elastic modulus (E) values are significantly increased over twofold following NLO CXL I and II compared with baseline values (P0.05). This data suggests that NLO CXL has a comparable effect to conventional UVA CXL in mechanically stiffening collagen and may provide a safe and effective approach to localize CXL at different regions and depths within the cornea.

  17. 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.

  18. [Evaluation of 138 fractures of the cervical spine during a recent 5-year period (1979 to 1983). Therapeutic approaches].

    Science.gov (United States)

    Reynier, Y; Lena, G; Diaz-Vazquez, P; Vincentelli, F; Vigouroux, R P

    1985-01-01

    138 cervical spine fractures are reviewed during a recent period of 5 years (1979-1983). Their frequency stay high. The serial concern 67% of men and 33% of women. We observe a peak age between 20 and 30 (23%). 65% of lesions are caused by a traffic injury, 27% by a falling down, 10% by a diving. 45% of cases interest the upper cervical spine (C1-C2) with a high proportion of odontoid process fractures (60%) and Hangman's fractures (30%); 54% of cases concern the lower cervical spine (C3-C7) with an important part of fracture-luxation (72%), specially C5-C6 (35%). Clinically, we note almost a same part of fractures without neurological disturbances (54%) and with neurological abnormalities (46%). In this situation, the sensitive and motor loss are often severe (78%). In 40%, the injuries are polytraumatism and association spine lesion, cranio-cerebral lesion is the most frequent (61%). In upper cervical spine fractures, after Crutchfield or Gardner traction, posterior fixation was performed (62%). The treatment was conservative in 30%. In lower cervical spine lesions, a secondary surgical approach by an antero-lateral way was made (53%). The treatment was initially surgical in 13% and conservative in 28%. The mortality rate of this pathology is important (22%; i.e. 30 deaths on 138 cases).

  19. 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.

  20. Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a 3D arteriole with in vivo comparison.

    Directory of Open Access Journals (Sweden)

    Weiwei Wang

    Full Text Available Cylindrical blood vessels, ellipsoid platelets and biconcave-shaped deformable erythrocytes (RBCs are important participants in hemostasis and thrombosis. However, due to the challenge of combining these components in simulation tools, few simulation studies have included all of them in realistic three-dimensional models. In the present study, we apply a recently developed simulation model to incorporate these components and analyze the flow in a thrombotic tubular arteriole, particularly the detailed hydrodynamic interactions between the thrombus shape, RBCs and platelets. It was found that at certain azimuth positions, the velocity drops in the proximity of both the upstream and downstream edge of the thrombus, which is accompanied by a rapid velocity increase in the narrowed region. The RBCs alter the flow profiles significantly from the typical low Reynolds (Re number flow, and also enhance the deposition of free flowing platelets onto the thrombus. By evaluating the platelet-thrombus interaction and platelet-RBC interaction together, several mechanisms of platelet deposition augmentation are identified. With in vivo data comparison, our model illustrates the potential of future thrombosis studies that incorporate detailed receptor-ligand adhesion modules.

  1. Usefulness of brain natriuretic peptide for predicting left atrial appendage thrombus in patients with unanticoagulated nonvalvular persistent atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Yusuke Ochiumi, MD

    2015-10-01

    Conclusions: In patients with unanticoagulated NVAF, a BNP level >251.2 pg/mL may be helpful for predicting the incidence of LAA thrombus and may be used as a surrogate marker of CHF. The BNP level is clinically useful for the risk stratification of systemic thromboembolism in patients with unanticoagulated NVAF.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  3. Ultrasound-guided laser ablation of incidental papillary thyroid microcarcinoma: a potential therapeutic approach in patients at surgical risk.

    Science.gov (United States)

    Papini, Enrico; Guglielmi, Rinaldo; Gharib, Hossein; Hosseim, Gharib; Misischi, Irene; Graziano, Filomena; Chianelli, Marco; Crescenzi, Anna; Bianchini, Antonio; Valle, Dario; Bizzarri, Giancarlo

    2011-08-01

    Incidental papillary thyroid microcarcinoma (PTMC), a frequent clinical problem, is usually associated with a favorable outcome. During long-term follow-up, only a minority of cases show aggressive behavior with either lymph node or distant metastases. Recently, we had an opportunity to evaluate the efficacy of nonsurgical, ultrasound (US)-guided percutaneous laser ablation (PLA) for local treatment of PTMC in an otherwise inoperable patient. Neck US examination revealed an incidental, solitary, 8 × 7 × 7 mm hypoechoic nodule with microcalcifications of the right thyroid lobe. The patient suffered from decompensated liver cirrhosis, renal failure, and recent surgery followed by external beam radiation therapy for breast cancer. Cytologic diagnosis showed papillary thyroid carcinoma, but the patient declined surgery because of high risk of thyroid surgery. After local anesthesia with 2% xylocaine, PLA was performed according to the previously reported procedure with an Nd:YAG laser. The procedure was well tolerated, without side effects, and the patient required no analgesics. US-guided fine-needle aspiration biopsy and core-needle biopsy were performed at 1 and 12 months after PLA, which demonstrated necrotic material and inflammatory cells with no viable neoplastic cell. At the 24 months US follow-up examination, the area of necrosis further decreased, demonstrating a 4 × 4 mm hypoechoic zone and a small hyperechoic area due to fibrotic changes. A fine-needle aspiration biopsy confirmed the absence of malignant cells. Laser-induced thermal ablation was a safe and effective ablative treatment for a patient with PTMC confined to the thyroid gland who was at high surgical risk. This approach should be considered only in elderly patients and/or in those with comorbidities that might expose the patients to an undue high surgical risk and only after the evaluation by neck US, computed tomography, magnetic resonance imaging, or positron emission tomography

  4. 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

  5. Role of presurgical targeted molecular therapy in renal cell carcinoma with an inferior vena cava tumor thrombus

    Directory of Open Access Journals (Sweden)

    Peng C

    2018-04-01

    Full Text Available Cheng Peng,1,* Liangyou Gu,1,* Lei Wang,2 Qingbo Huang,1 Baojun Wang,1 Gang Guo,1 Yang Fan,1 Yu Gao,1 Xin Ma,1 Xu Zhang1 1Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, People’s Republic of China; 2Department of Urology, Chinese PLA 534 Hospital, Luoyang, People’s Republic of China *These authors contributed equally to this work Purpose: The clinical benefit of targeted molecular therapy (TMT in renal cell carcinoma (RCC with an inferior vena cava (IVC tumor thrombus remains controversial. The aim of this study was to investigate the effects of presurgical TMT on the heights and levels of IVC thrombi, and to assess its impact on surgical strategy. Patients and methods: We retrospectively reviewed data from 18 patients with RCC involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy. The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging. Clinicopathological factors were also evaluated to assess their association with TMT efficacy. Results: The tumor thrombus levels before TMT were stage I in 1 patient (5.6%, II in 12 patients (66.7%, III in 4 patients (22.2%, and IV in 1 patient (5.6%. After a median of two treatment cycles (range: 1–3, the thrombus height decreased measurably in 11 patients (61.1% with an average shrinkage of 17.7%. The thrombus height remained stable in five patients (27.8% and was enlarged in two (11.1%. Downstaging of the thrombus level occurred in four patients (22.2%; the surgical strategy was modified in three patients (16.7% to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy. Furthermore, a higher neutrophil count tended to be associated with a worse clinical TMT-associated outcome (P=0.056. Conclusion: Our data suggest a limited influence of presurgical TMT

  6. Late Thrombolytic Treatment In A Patient With Ischemic Stroke Caused By Biatrial Thrombus

    Directory of Open Access Journals (Sweden)

    Halit CINARKA

    2015-07-01

    Full Text Available Venous thromboembolism is a preventable disease when necessary precautions are taken and it occurs along with deep vein thrombosis and pulmonary embolism. Mortality related to venous thromboembolism may be high in the acute phase of the disease and it may become chronic. Intracardiac thrombus may be detected in some venous thromboemboli cases. Cardiac embolism is responsible for most of the ischemic strokes which can be very mortal or may cause serious morbidity when they are not treated in time. In this report, we aimed to present the results of late antithrombolytic treatment in a 77-year old patient who developed deep vein thrombosis, biatrial thrombosis and ischemic stroke following hydrocephalus shunt operation.   Key words: Venous thromboembolism; ischemic stroke; thrombolytic therapy

  7. The short-term prognostic value of thrombus precursor protein in patients with unstable angina

    International Nuclear Information System (INIS)

    Shen Yanbo; Yu Yan; Tang Jianzhong; Yuan Dingshan; Cai Danlei

    2005-01-01

    Objective: To investigate the short-term prognostic value of thrombus precursor protein (TpP) in patients with unstable angina (UA). Methods: One hundred and ten cases of UA were selected. The TpP was measured by enzyme linked immunosorbent assay (ELISA). The cardiovascular events were observed in 6 months. Results: In the 100 cases of UA, the cardiovascular events were observed in 17 cases. There was an significant difference in three levels of TpP (P<0.05). The risk level was increasing as the increasing of the plasma level of TpP. Conclusion: The level of TpP has certain reference value and plays a role in forecasting of the short-term prognosis of the patients with UA. When the plasma level of TpP increases there is also an increase in OR. (authors)

  8. The abdominal aortic aneurysm and intraluminal thrombus: current concepts of development and treatment

    Directory of Open Access Journals (Sweden)

    Aleksandra ePiechota-Polańczyk

    2015-05-01

    Full Text Available The pathogenesis of the abdominal aortic aneurysm (AAA shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the accumulation of neutrophils in the intraluminal thrombus and their central role in creating an oxidative and proteolytic environment. Particular focus is placed on the controversial role of heme oxygenase 1/carbon monoxide and nitric oxide synthase/peroxynitrite which may exert both protective and damaging effects in the development of the aneurysm. Treatment indications as well as surgical and pharmacological options for AAA therapy are discussed in light of recent reports.

  9. Accurate diagnosis of iliac vein thrombosis in pregnancy with magnetic resonance direct thrombus imaging (MRDTI).

    Science.gov (United States)

    Dronkers, Charlotte E A; Srámek, Alexandr; Huisman, Menno V; Klok, Frederikus A

    2016-12-13

    A pregnant woman aged 29 years, G1P0 at 21 weeks of gestation of a dichorionic diamniotic twin, presented with suspected deep vein thrombosis (DVT) of the left leg. Repeated (compression) ultrasonography was not diagnostic for DVT but showed reduced flow over the left external iliac vein, common femoral vein and superficial femoral vein. In pursue of a definite diagnosis, magnetic resonance direct thrombus imaging was performed showing a clear high signal in the left common iliac vein which is diagnostic for acute thrombosis in this venous segment. Phase contrast venography supported this diagnosis, showing no flow in the left common iliac vein. Treatment with anticoagulants was started. 6 months after the diagnosis, the patient is doing well and does not report signs of post-thrombotic syndrome. 2016 BMJ Publishing Group Ltd.

  10. Exercise Training in a Patient With a Left Ventricular Assist Device and Large Aortic Valve Thrombus.

    Science.gov (United States)

    Wuliya, Mijiti; Peyrot, Sandrine; Radu, Costin; Deux, Jean-François; Ben Elhaj, Habib; Lellouche, Nicolas; Damy, Thibaud; Guendouz, Soulef; Gellen, Barnabas

    2017-11-01

    An aortic valve thrombus (AVT) is a rare complication after HeartMate II implantation. In a 44-year-old man, a large AVT was discovered 6 weeks after implantation of a HeartMate II for severe dilated cardiomyopathy. The aortic valve was permanently closed. After a followup of 3 months without embolic events, the patient started a cardiac rehabilitation (CR) program involving aerobic exercise, resistance exercises, group gymnastics, and relaxation exercise, and completed the program without any complications, resulting in a significant functional benefit. CR might not be systematically contraindicated in patients with HeartMate II and an AVT, in particular, if there is no opening of the aortic valve at rest.

  11. Development of real-time and quantitative monitoring of thrombus formation in an extracorporeal centrifugal blood pump

    Science.gov (United States)

    Sakota, Daisuke; Fujiwara, Tatsuki; Ohuchi, Katsuhiro; Kuwana, Katsuyuki; Yamazaki, Hiroyuki; Kosaka, Ryo; Maruyama, Osamu

    2018-02-01

    We developed an optical detector of thrombus formed on the pivot bearing of an extracorporeal centrifugal blood pump (MERA HCF-MP23; Senko Medical Instrument Mfg. Co., Ltd., Tokyo, Japan) which is frequently used for long-term extracorporeal circulation support to bridge to an implantable artificial heart, which in turn is used for bridge to heart transplantation in Japan. In this study, we investigated the quantitative performance of the thrombus formation in acute animal experiments. A total of three experiments of extracorporeal left ventricular assist using Japanese specific pathogen-free pigs were conducted. The optical fibers were set in the pump driver unit. The incident light at nearinfrared wavelength aiming at the pivot bearing and the resulting scattered light were guided to respective fibers. The detected signal was analyzed to obtain thrombus formation level (TFL) calculated by a specially developed software. When the increase in TFL was confirmed, the pump was exchanged and the extracorporeal circulation was restarted. The number of pump exchanges were four times at each experiment so a total of twelve pumps were evaluated. 3-dimentional data surrounding the pivot bearing and the adhered thrombus was captured by a 3-dimantional surface measurement system to calculate the thrombus surface area (TSA) formed on the pivot bearing. As a result, the correlation coefficient between TFL and TSA was 0.878. The accuracy of TSA estimated by the optical detector was 3.6+/-2.3 mm2. This was small enough to not have the pump exchanged in clinical judgement. The developed detector would be useful for optimal anti-coagulation management.

  12. Role of protein kinase CK2 in the dynamic interaction of platelets, leukocytes and endothelial cells during thrombus formation.

    Science.gov (United States)

    Ampofo, Emmanuel; Müller, Isabelle; Dahmke, Indra N; Eichler, Hermann; Montenarh, Mathias; Menger, Michael D; Laschke, Matthias W

    2015-11-01

    Thrombus formation is a complex process, which is characterized by the dynamic interaction of platelets, leukocytes and endothelial cells. The activation of these cells is strictly mediated by different phospho-regulated signaling pathways. Recently, it has been reported that inhibition of protein kinase CK2 affects platelet function by suppressing phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K) signaling. Based on this finding, we herein analyzed whether CK2 acts as a crucial regulator of thrombus formation. We examined the effect of CK2 inhibition on platelet activation and aggregation, the formation of platelet-leukocyte aggregates (PLA), the endothelial expression of von Willebrand factor (vWF), intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the subcellular localization of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and phospho-p65 in human dermal microvascular endothelial cells (HDMEC). Dorsal skinfold chambers were prepared in BALB/c mice to analyze in vivo the effect of CK2 inhibition on photochemically induced thrombus formation using intravital fluorescence microscopy. CK2 inhibition by CX-4945 suppressed adenosin diphosphate (ADP)- and proteinase-activated receptor-1-peptide (PAR-1-AP)-stimulated platelet aggregation, which was associated with down-regulation of P-selectin, GPIIb/IIIa and a reduced formation of PLA. Expression and secretion of vWF was diminished in CX-4945-treated HDMEC. Moreover, CK2 inhibition attenuated the endothelial expression of VCAM-1, whereas the expression of ICAM-1 was not affected. Finally, CX-4945-treated mice exhibited a significantly delayed photochemically induced thrombus formation when compared to vehicle-treated controls. These results indicate that CK2 is a pleiotropic regulator of thrombus formation, affecting multiple interactions of platelets, leukocytes and endothelial cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. The effects of cigarette smoke and nicotine on platelet thrombus formation in stenosed dog coronary arteries: inhibition with phentolamine.

    Science.gov (United States)

    Folts, J D; Bonebrake, F C

    1982-03-01

    This study was undertaken to examine in vivo the effects of cigarette smoke on cyclic reductions in coronary flow due to platelet thrombus formation in the stenosed coronary arteries of anesthetized dogs. The circumflex coronary artery of 21 mongrel dogs was stenosed 60 - 80%, with blood flow measured with an electromagnetic flow probe. After the administration of cigarette smoke, plasma epinephrine was elevated nine times the control level (p less than 0.001) and peak mean blood pressure was elevated one and one-half times control (p less than 0.01). The hematocrit increased several percent (p less than 0.01) with cigarette smoke, although blood gases and pH remained unchanged. In all 21 dogs, spontaneous reductions in coronary blood flow were greatly exacerbated in the stenosed circumflex artery as evidenced by the number of flow reductions, the increased size of the reductions and the rate of flow reduction. Nicotine administered intravenously in doses comparable to those achieved through absorption of cigarette smoke by the lungs provoked similar responses of alpha-adrenergic stimulation and potentiation of the platelet thrombus formation. An alpha-adrenergic antagonist, phentolamine, was given (3 mg/kg) intravenously to inhibit the exacerbated platelet thrombus formation due to cigarette smoke or infused nicotine. In 18 of 21 dogs, an acute occlusive platelet thrombus was prevented 15 minutes after phentolamine and after phentolamine and after a cigarette smoke or nicotine challenge. This study confirms a link between cigarette smoking, platelet formation, and the potential for humans to develop an acute occlusive platelet thrombus in a diseased and stenotic coronary artery.

  14. Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA, an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f. var. glaucocalyx (Maxim. Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01 μg/ml, 0.1 μg/ml significantly inhibited platelet aggregation induced by collagen (P<0.001 and CRP (P<0.01, a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent.

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

    Science.gov (United States)

    Westphal, Glauco Adrieno

    2016-02-01

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

  16. Coronary embolism causing acute inferior wall and ventricular myocardial infarction in a patient with rheumatic valvular heart disease: treatment with thrombus aspiration.

    Science.gov (United States)

    Du, Xiao-Yu; Hui, Peng; Zheng, Yang

    2015-06-26

    An elderly man with rheumatic valvular heart disease and atrial fibrillation presented with acute myocardial infarction. A coronary angiogram revealed complete occlusion of the right coronary artery (RCA), and we therefore considered that a thrombus might have obstructed the ostium of the RCA. We used a guiding catheter and the syringe of an aspiration device to remove two large dark red thrombi. A subsequent angiogram revealed that blood flow through the RCA had recovered, and the endomembrane of the RCA was smooth, with no evidence of stenosis or residual thrombus. In this case, thrombus aspiration via a guiding catheter was efficacious for treating this type of coronary embolism.

  17. 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.

  18. 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.

  19. Therapeutic Gardening

    OpenAIRE

    Turner, Phyllis; Fox, Laurie; Parkhurst, James A. (James Albert)

    2013-01-01

    Gardening can be therapeutic for anyone and has been used as therapy for those with physical, emotional and social disabilities, for children, and for those who are elderly. Through careful adaptations to the garden, the gardener and the plants, almost anyone can benefit from the activity of gardening

  20. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    thereby increasing enzyme activity and cellular function, reducing substrate and stress on cells.15 ... detection of rejection at its earliest stages16, nullifying foreign antigen processing and detection and induction .... electro-coagulation of functional cortex24, use of isolated or combined fine laser treatment for ocular visual.

  1. 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 ...

  2. 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.

  3. Therapeutic approach to primary malignant epithelial tumors of the liver in childhood: results of the Italian retrospective study and literature survey.

    Science.gov (United States)

    Perilongo, G; Carli, M; Guglielmi, M; De Bernardi, B; Bellani, F F; Paolucci, G; Pianca, C; Madon, E; Calculli, G; Ceci, A

    1987-01-01

    We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellular carcinomas (HPCs) occurring in patients less than 19 years old, admitted to the Italian retrospective multicentric study, conducted between 1983 and 1985, on childhood malignant hepatic tumors. The median ages of the patients with HPB and HPC at diagnosis were 22.34 months and 96.23 months, respectively, with a male/female ratio of 0.7 and 1.7, respectively. Fourteen HPBs (61%) and 5 HPCs (31%) achieved surgical complete remission (CR). Of these, 11 HPB and all 5 HPC are still in CR with a median follow-up of 36 months and 3.5 years, respectively. One HPB and 1 HPC became resectable after a primary course of cis-platinum alone in the case of HPB and used with VP-16 in the case of HPC. All of the 9 HPBs and 11 HPCs, who never achieved CR, died of disease at a median interval from diagnosis of 5 and 2 months, respectively. The published therapeutic approaches for these tumors were also reviewed.

  4. Targeting α4β2 nAChRs in CNS disorders: Perspectives on positive allosteric modulation as a therapeutic approach

    DEFF Research Database (Denmark)

    Grupe, Morten; Grunnet, Morten; Bastlund, Jesper F.

    2015-01-01

    The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional character...... clinical advantages and concerns of PAMs are discussed in the light of the role of α4β2 nAChRs as key regulators of fast synaptic transmission.......The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional...... be used as a treatment approach in various CNS disorders. As subtype-selective agonists and other cholinergic ligands have only shown limited therapeutic success, the focus of recent drug development endeavours has largely shifted to positive allosteric modulators (PAMs). By potentiating the action...

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

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

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

  6. 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

  7. The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney.

    Science.gov (United States)

    Kawasaki, Takashi; Chaudry, Irshad H

    2012-12-01

    Several clinical studies show a gender dimorphism of immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. However, there are conflicting reports on the role of gender in outcomes. Animal studies of shock, trauma, and sepsis have confirmed that alterations in immune and organ functions are more markedly depressed in adult males and in ovariectomized and aged females. In this review, we discuss the effect of estrogen on liver, intestinal, splenic, and renal functions in an experimental model of sepsis, trauma, and reperfusion injury. To establish the role of gender in the outcome of these patients, more studies in clinical and experimental settings are required to determine whether gender-specific responses are global across the injuries or are observed in specific injury situations. Studies are also needed to delineate underlying mechanisms responsible for differences between males and females. The findings gained from the experimental studies will help in designing innovative therapeutic approaches for the treatment of sepsis, trauma, and reperfusion injury patients.

  8. 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.

  9. Mining the Proteome ofFusobacterium nucleatumsubsp.nucleatumATCC 25586 for Potential Therapeutics Discovery: AnIn SilicoApproach.

    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 .

  10. 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.

  11. Characterization of an experimental venous thrombus model with MRI, phlebography and histology; Charakterisierung eines experimentellen venoesen Thrombosemodels mittels MRT, Phlebographie und Histologie

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, S.A. [Klinik und Hochschulambulanz fuer Radiologie und Nuklearmedizin, Charite - Universitaetsmedizin Berlin (Germany); Imaging Sciences Dept., Hammersmith Hospital, Faculty of Medicine, Imperial College London (United Kingdom); Schiffler, S.; Gust, R.; Winterhalter, S.; Wolf, K.J. [Klinik und Hochschulambulanz fuer Radiologie und Nuklearmedizin, Charite - Universitaetsmedizin Berlin (Germany); Coupland, S.E. [Institut fuer Pathologie, Charite - Universitaetsmedizin Berlin (Germany)

    2005-03-01

    Introduction: Several magnetic resonance (MR) techniques designed to demonstrate the characteristic signal intensity of blood degeneration products of thrombi have been suggested, but the effect of thrombus organization on the MR display, in particular with regard to its temporal evolution, remains to be determined. It is the purpose of this study to develop a stagnation thrombus model in rabbits and to characterize thrombus at different ages with two (MR) imaging techniques, phlebography and histology. Materials and Methods: Venous stagnation thrombi were induced in the external jugular veins of rabbits usi